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Oral use of Swedish moist snuff (snus) and risk for cancer of the mouth, lung, and pancreas in male construction workers: A retrospective cohort study
Abstract
Although classified as carcinogenic, snuff is used increasingly in several populations. Scandinavian moist snuff (snus) has been proposed as a less harmful alternative to smoking, but precise data on the independent associations of snus use with site-specific cancers are sparse. We aimed to assess the risks for cancer of the oral cavity, lung, and pancreas.
Detailed information about tobacco smoking and snus use was obtained from 279 897 male Swedish construction workers in 1978-92. Complete follow-up until end of 2004 was accomplished through links with population and health registers. To distinguish possible effects of snus from those of smoking, we focused on 125 576 workers who were reported to be never-smokers at entry. Adjusted relative risks were derived from Cox proportional hazards regression models.
60 cases of oral, 154 of lung, and 83 of pancreatic cancer were recorded in never-smokers. Snus use was independently associated with increased risk of pancreatic cancer (relative risk for ever-users of snus 2.0; 95% CI 1.2-3.3, compared with never-users of any tobacco), but was unrelated to incidence of oral (0.8, 95% CI 0.4-1.7) and lung cancer (0.8, 0.5-1.3).
Use of Swedish snus should be added to the list of tentative risk factors for pancreatic cancer. We were unable to confirm any excess of oral or lung cancer in snus users.
... One of them was a pooled analysis of nine Swedish cohorts reporting an oral cancer risk of HR 0.93 (95% CI 0.59 to 1.44, 25 exposed cases). 25 This most recent and pooled study from 2021 was used for the GRADE evaluation (Table S3) Construction Workers Cohort (CWC), used separately in an earlier oral cancer study by Luo et al. 20 The most recent one had a maximum follow-up of 35 years and showed an oral cancer risk of HR 1.0 (95% CI 0.6 to 1.7, number of exposed cases not reported). The third study on oral cancer, reported a risk estimate for oral and pharyngeal cancers combined, restricted to never smoking, daily snus users, showing a risk of HR 2.3 (95% CI 0.7 to 8.3, 5 exposed cases). ...
... Luo et al 20 based their analysis on never smoking CWC participants and reported a RR of 2.1 (95% CI 1.2 to 3.6, 18 exposed cases) among current users of snus at baseline with a maximum of 27 years follow-up (Table 1). 20 In a more recent pooled analysis of nine Swedish cohorts, where 2/3 of all participants and 72% of incident cases or deaths of pancreatic cancer originated from the CWC, the estimated risk in current users of Swedish snus at baseline was HR 1.07 (95% CI 0.77 to 1.50, 41 exposed cases) in a sensitivity analysis restricted to never smokers (Table 1). 23 .60:4 ...
... The alternative approach, with adjustment for smoking in analyses of study samples that also include smokers and dual users, has been shown to distort risk estimates for snus users most likely because of residual confounding by smoking. This was illustrated by Luo et al, 20 who chose a priori to analyze exclusive users of snus compared with participants who had never smoked. Dual users of cigarettes and snus with nicotine dependency, would tend to replace any reduction of their cigarette consumption with snus, and vice versa to obtain a more stable serum nicotine concentration. ...
The main objective of this systematic review was to assess cancer risk, and mortality after cancer diagnosis, for exclusive users of Swedish snus, compared with non‐users of tobacco. We followed international standards for systematic reviews and graded our confidence in the risk estimates using the GRADE approach. Our search gave 2450 articles, of which 67 were assessed in full text against our inclusion criteria. Of these, 14 cohort‐studies and one case‐control study were included in the review. The studies investigated risk of cancer in the oral cavity or oropharynx (3 studies), esophagus (1 study), stomach (1 study), pancreas (2 studies), colorectum (2 studies), anus (1 study) and lung (1 study), as well as malignant lymphoma (1 study), leukemia and multiple myeloma (1 study), melanoma (1 study), any cancer (1 study) and mortality after cancer diagnosis (4 studies). Cancer risk could only be evaluated in men as there was a general lack of data for women. All included studies were evaluated to have a moderate risk of bias, mostly related to validity of exposure information. An increased risk of cancer of the esophagus, pancreas, stomach and rectum as well as an association between use of snus and increased mortality after a cancer diagnosis was reported. Our confidence in the various risk estimates varied from moderate through low to very low.
... The International Agency for research on cancer (IArc), in 2007, hence concluded that there is strong evidence that smokeless tobacco causes cancer of the oral cavity [8]. The relationship between use of the Swedish snus and oral cancer is, however, less clear [9][10][11][12][13][14][15]. ...
... The ScHeSu has previously investigated the impact of snus use on multiple health outcomes such as pancreatic cancer [18], colorectal cancer [19], diabetes [20] and Parkinson's disease [21]. The present ScHeSu involves data from nine Swedish cohort studies [9,[22][23][24][25][26][27][28][29], of which only one [9] had published data on snus use and oral cancer. We here take advantage of this large pooling project to investigate the impact of snus use on oral-cancer risk. ...
... The ScHeSu has previously investigated the impact of snus use on multiple health outcomes such as pancreatic cancer [18], colorectal cancer [19], diabetes [20] and Parkinson's disease [21]. The present ScHeSu involves data from nine Swedish cohort studies [9,[22][23][24][25][26][27][28][29], of which only one [9] had published data on snus use and oral cancer. We here take advantage of this large pooling project to investigate the impact of snus use on oral-cancer risk. ...
Aims: Worldwide, smokeless-tobacco use is a major risk factor for oral cancer. Evidence regarding the particular association between Swedish snus use and oral cancer is, however, less clear. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between snus use and oral cancer. Methods: A total of 418,369 male participants from nine cohort studies were followed up for oral cancer incidence through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. Results: During 9,201,647 person-years of observation, 628 men developed oral cancer. Compared to never-snus use, ever-snus use was not associated with oral cancer (adjusted HR 0.90, 95% CI: 0.74, 1.09). There were no clear trends in risk with duration or intensity of snus use, although lower intensity use (⩽ 4 cans/week) was associated with a reduced risk (HR 0.65, 95% CI: 0.45, 0.94). Snus use was not associated with oral cancer among never smokers (HR 0.87, 95% CI: 0.57, 1.32). Conclusions: Swedish snus use does not appear to be implicated in the development of oral cancer in men.
... There are two epidemiological studies, that have reported the potential effects of snus use on lung cancer risk [31,32]. One study [31] retrospectively analysed Percentage prevalence of daily tobacco "smoking" (*defined as the use of "boxed" cigarettes, hand-rolled cigarettes, cigarillos, cigars and pipe tobacco) across EU countries. ...
... There are two epidemiological studies, that have reported the potential effects of snus use on lung cancer risk [31,32]. One study [31] retrospectively analysed Percentage prevalence of daily tobacco "smoking" (*defined as the use of "boxed" cigarettes, hand-rolled cigarettes, cigarillos, cigars and pipe tobacco) across EU countries. Produced using data taken with permission from [9]. ...
... Two earlier epidemiological studies [31,32] reported an association between snus use and an increased risk of pancreatic cancer. One study [31] retrospectively analysed data from a large cohort of Swedish construction workers (n = 125,576) and although no association was reported for the whole population (RR 0.9, 0.7-1.2), a RR of 2.0 (95% CI 1.2-3.3) ...
Snus is an oral smokeless tobacco product which is usually placed behind the upper lip, either in a loose form or in portioned sachets, and is primarily used in Sweden and Norway. The purpose of this review is to examine the reported effects of snus use in relation to specified health effects, namely lung cancer, cardiovascular disease, pancreatic cancer, diabetes, oral cancer and non-neoplastic oral disease. The review also examines the harm reduction potential of snus as an alternative to cigarettes by comparing the prevalence of snus use and cigarette smoking, and the reported incidence of tobacco-related diseases across European Union countries. The scientific literature generally indicates that the use of snus is not a significant risk factor for developing lung cancer, cardiovascular disease, pancreatic cancer or oral cancer. Studies investigating snus use and diabetes have reported that high consumption of snus (estimated as being four or more cans per week) may be associated with a higher risk of developing diabetes or components of metabolic syndrome; however, overall results are not conclusive. Snus use is associated with the presence of non-neoplastic oral mucosal lesions which are reported to heal rapidly once use has stopped. The most recent Eurobarometer data from 2017 reported that Sweden had the lowest prevalence of daily cigarette use in the European Union at 5% whilst daily "oral tobacco" use was reported to be 20%. European data published by the World Health Organisation in 2018 indicated that Sweden had the lowest rate of tobacco-related mortality and the lowest incidence of male lung cancer. Overall, prevalence statistics and epidemiological data indicate that the use of snus confers a significant harm reduction benefit which is reflected in the comparatively low levels of tobacco-related disease in Sweden when compared with the rest of Europe. The available scientific data, including long-term population studies conducted by independent bodies, demonstrates that the health risks associated with snus are considerably lower than those associated with cigarette smoking.
... 14 General health effects Compared to cigarette smoking, prospective cohort studies suggest both a lower risk of overall mortality and many tobacco-related diseases amongst snus users. 2,[15][16][17][18][19] As snus is not combusted and inhaled, respiratory sequelae seen with cigarette smoking, such as chronic obstructive pulmonary disease, are generally avoided. Notwithstanding, there appears to be residual risk for development of cardiovascular disease and pancreatic cancer, compared to non-users. ...
... Notwithstanding, there appears to be residual risk for development of cardiovascular disease and pancreatic cancer, compared to non-users. 15,[20][21][22][23] Cardiovascular risk is associated more with the duration of use, rather than the quantity used. 6 Oral health effects of snus use From about 2019, a handful of cases of snus-induced oral mucosal lesions began being seen in the Auckland Regional Hospital & Specialist Dentistry (HSD) oral medicine clinics. ...
Innovative products are constantly appearing in the consumer market, more colourful, exciting, and appealing as ever. Unfortunately, this extends to the tobacco industry. Novel tobacco products are marketed, often with the buy-line that they have fewer harms than conventional cigarette smoking. But are they always less harmful? And are they always new? This article raises awareness of snus, a smokeless tobacco and nicotine product,
that made a fleeting market presence in New Zealand from 2018 to 2020 and
induces unique oral mucosal and gingival pathologies. It was available for purchase
over-the-counter in settings such as vape and liquor stores. In 2020 an amendment
to New Zealand smoking legislation (the Smokefree Environments and Regulated
Products (Vaping) Amendment) made the advertisement and importation for sale
of oral nicotine products illegal under the Act. However, alongside other tobacco-related
products, such as chewing tobacco and snuff, snus remains legal to import
for personal use through international mail, without permit.
... However, this stance is not only based on a comparison of the risks of using snus relative to smoking cigarettes; the health risk when using snus overall is also a central concern. Studies have found a slightly increased risk for pancreatic cancer (Luo et al., 2007) and type 2 diabetes (Carlsson et al., 2017), but no evidence for oral or lung cancer (Luo et al., 2007), colorectal cancer (Nordenvall et al., 2010) or cardiovascular diseases (Hansson, 2009). In spite of the scarce scientific evidence the EU tried to strengthen the risk message on snus cans by changing "can damage" in "This tobacco product can damage your health and is addictive" to simple "damages" (Directive 2014/40/EU). ...
... However, this stance is not only based on a comparison of the risks of using snus relative to smoking cigarettes; the health risk when using snus overall is also a central concern. Studies have found a slightly increased risk for pancreatic cancer (Luo et al., 2007) and type 2 diabetes (Carlsson et al., 2017), but no evidence for oral or lung cancer (Luo et al., 2007), colorectal cancer (Nordenvall et al., 2010) or cardiovascular diseases (Hansson, 2009). In spite of the scarce scientific evidence the EU tried to strengthen the risk message on snus cans by changing "can damage" in "This tobacco product can damage your health and is addictive" to simple "damages" (Directive 2014/40/EU). ...
Purpose
Health promotion strategies often attempt to change people’s behavior through targeting their risk perceptions. These perceptions may, however, be moderated by other factors. This study therefore aimed at investigating the trustworthiness and consistency of risk information, as well as respondent perceptions of the adequacy of amount received among a representative sample of former smokers, and how this information is related to gender, age, education level and whether using nicotine or not.
Design/methodology/approach
The respondents are part of a seven-year follow-up of former smokers in Sweden. Initially, 1400 respondents were contacted, whereof 705 (response rate 50%) answered a Web-survey. The majority (85 %) was still nicotine-free but some made use of nicotine in different forms. The data analysis includes descriptive statistics and logistic regressions.
Findings
Most respondents trusted risk information whether offered by the public authorities or came from other sources such as media, and generally perceived that there was an adequate amount. However, there were some differences between the products, where quite a few distrusted information on Nicotine Replacement Therapies (NRTs) and some perceived the information on snus and NRTs as contradictory and too little.
Originality/value
Knowledge about how former smokers perceive information regarding negative aspects of cigarette use may facilitate more effective risk communication with current smokers, and it may also be important for communicating information about other nicotine products to those who are trying to or who already have quit smoking.
... Cigarette smoke has been associated with gum inflammation/disease, tooth loss, cancer and tooth staining [2,3]. Studies have shown there is minimal or no increased risk of oral cancer associated with smokeless tobacco use [4][5][6][7]. In addition, a recent chemical analysis reported that MOPs have lower toxicant levels compared to Swedish-style snus products [8]. ...
... The reduced harm potential of Swedish-style snus has been clearly demonstrated [4][5][6][7], by extension, tobacco free-MOPs, with nicotine levels comparable to levels found in Swedish-style snus, could be expected to have similar or greater harm reduction potential and therefore, this study contributes to the underpinning science used to determine the risk profile of the emerging MOPs category as an alternative to smoking. The data produced in this study demonstrate that LYFT are less cytotoxic, across multiple flavour variants and nicotine strengths, than an equivalent reference snus product and comparator products which can be replicated in both H292 s and HGFs. ...
In many regulated industries there is an increasing pressure to provide timely and robust risk assessment data to support product launches. Real-time cell analysis (RTCA) is a tool that allows for the fast and relatively labour-free cytotoxic assessment of test compounds, compared to traditional methods. Here, we propose an application for the RTCA platform to provide a screening approach, to evaluate the cytotoxic potential of tobacco-free nicotine pouches, also termed modern oral product (MOP), to determine the contribution of differing nicotine strengths (4-11 mg) and a range of available flavour types from multiple markets, on overall product toxicity.
Aqueous extracts were prepared for all products using 1 pouch in 20 ml cell culture media and applied to the cell system for 24 hours. Test extract nicotine concentrations reflected the increases in product nicotine strength; however, these changes were not present in the same magnitude in the cytotoxicity data obtained from both primary human gingival fibroblasts (HGF) and an NCI-H292 human bronchial epithelial continuous cell line. Furthermore, across the range of flavours and product nicotine strengths tested, H292 cells whilst not the target organ for oral product use, accurately predicted the results seen in HGFs and could be considered a useful surrogate for fast screening studies. H292 cells are more easily cultured and for longer periods, offering a more compatible test system.
In conclusion, the data demonstrate the utility of the RTCA platform for the quick assessment of a large range of product variants. Furthermore, for a cytotoxicity measure with this test product, the simple H292 cell line can predict outcomes in the more complex HGF and provide useful preclinical cytotoxicity screening data to inform the risk assessment of MOPs and the relative contribution of flavourings, nicotine and other components.
... Smoking tobacco is available in bidis, cigarettes, roll-your-owns, sticks, pipes, water pipes, and kreteks [6]. Various research demonstrated that smoking tobacco is connected with lung cancer, pancreatic cancer, mouth cancer, cardiovascular, and other disorders [7,8]. It has been established that oral and esophageal cancers are listed worldwide as the sixth most prevalent malignancies among both genders; however, as per statistics, oral and esophageal cancers are classified as the third most common type of cancer in nations such as India, Nepal, and the UK [1,[9][10][11][12][13]. ...
Introduction
Tobacco addiction is widely recognized as the most significant menace to both systemic and oral diseases, resulting in around eight million fatalities worldwide annually. The current investigation was conducted to assess the influence of tobacco cessation counseling on the quality of life linked to oral health and to identify obstacles to quitting among those who use tobacco.
Methods
This observational, follow-up study was carried out among patients referred to the tobacco cessation unit for the cessation of their smoking tobacco habit. Data on the participants was collected in two phases. Oral health-related quality of life (OHRQoL) was assessed at baseline and again three months after quitting smoking habits in the second phase. The assessment of barriers to quitting was done by asking a few questions of all participants. A student t-test and a chi-square test were applied with a p-value <0.05 considering significance.
Results
The study comprised a total of 322 patients, ranging in age from 18 to 62, with a mean age of 32.58 ± 12.901 years. After three months of quitting tobacco, a comparison of the mean scores of the Oral Health Impact Profile (OHIP) domains revealed a significant reduction in the mean score across all domains. The reduction was statistically significant, with a p-value of 0.001. Upon investigating the association between obstacles to quitting tobacco and socioeconomic position, it was discovered that the expense of quitting aids or tobacco programs, as well as the likelihood of weight gain, were strongly linked to the socioeconomic status of the individuals involved in the study.
Conclusion
Based on the results, the present study concluded that oral health-related quality of life significantly improved after quitting.
... The present study included 14 cohort studies and three patient-control studies (Table 2) [16,[30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46]. Of these, 16 studies were conducted in Sweden, one in the US, and one in Norway. ...
... However, these products were later withdrawn from the market due to concerns of safety as these have been associated with diseases of the oral cavity, oral cancers, pancreatic cancers, cardiovascular diseases and reproductive problems. [9] Then, the search for clean nicotine delivery systems that would satisfy nicotine craving and promote the smoking cessation lead to the development of E-cigarettes. ...
... Tobacco consumption in any form can cause a variety of health issues, impacting multiple body systems. These can range from respiratory, cardiovascular, gastrointestinal systems to various oral mucosal alterations [1]. As a result, Tobacco smoking is one of the most significant risk factors for the occurrence of oral mucosal pre-cancerous and cancerous lesions [2]. ...
Background: Tobacco smoking is considered as one of the most common risk factors for development of oral mucosal lesions which may carry a potential risk for development of oral cancer. Objective: To find the prevalence of nicotinic stomatitis in a sample of cigarette and water pipe smokers in Erbil city of Iraq. Patients and Methods: This study included 410 smokers aged 18 years and above who are smoking for at least five years. Cigarette, water pipe and dual smokers were included of both genders. The type, duration and frequency of habit were recorded. The diagnosis of nicotinic stomatitis was done clinically. The data entered and analyzed by (SPSS software 25th version). Results: Majority of participants were cigarette smokers (73.7%).Out of 410 smoker, prevalence of nicotinic stomatitis was (55.3%) in cigarette smokers,(24.6%) in dual smokers while none of water pipe users developed nicotinic stomatitis ;the incidence increase with increase in duration and frequency of the habit. Conclusion: In this study we found cigarette smoking was more commonly practiced than water pipe .Nicotinic stomatitis is more prevalent in cigarette smoking and its incidence increased with duration and frequency of the habit.
... The published evidence regarding the association of oral cancer with tobacco use has primarily focused on combustible cigarettes and smokeless tobacco (ST) products. Previous studies have shown a consistent association between cigarette use and elevated risks of oral cancer [9][10][11][12]. For example, a meta-analysis by Gandini found substantially elevated risk of oral cavity cancer (relative risk (RR) = 3.43, 95% CI: 2.37-4.94 ...
Background
Tobacco use has been identified as a risk factor for oral cancer worldwide. However, oral cancer risk among people who smoke cigarettes, use smokeless tobacco products (ST), have transitioned from cigarettes to ST (“switchers”) or quit both cigarettes and/or ST (“quitters”) has not been well studied. This study compared oral cancer incidence between 2014–2017 relative to never tobacco use.
Methods
We estimated incidence rates and incidence rate ratios using data from state-wide cancer registries (i.e., Colorado, Florida, North Carolina, and Texas) and population counts derived from national surveys. A random-effect meta-analysis approach was used to summarize estimates among these groups, based on multiple imputation-based incidence rate ratio estimates, by state and age groups while considering potential heterogeneity.
Results
A total of 19,536 oral cancer cases were identified among adult males 35 years and older in the study geographies and period. People who currently smoked cigarettes were 2.6 (95% CI = 2.0-3.3) times as likely to be diagnosed with oral cancer compared to individuals who currently used ST. The incidence rate ratio among people who currently smoke cigarettes was 3.6 (95% CI = 3.2–4.1) relative to never users, 2.4 (95% CI = 1.8–3.1) relative to switchers and 1.4 (95% CI = 1.0-2.1) among switchers relative to quitters. The incidence rate ratio of current users of ST relative to never-users was 1.4 (95% CI = 1.1–1.9).
Conclusions
Findings from this population-based study with a large number of oral cancer cases support lower risk of oral cancer among users of ST compared to cigarettes. Compared to those who continue to smoke, oral cancer risks can be reduced by switching to ST products or quitting all tobacco.
... Tobacco consumption in any form can cause a variety of health issues, impacting multiple body systems. These can range from respiratory, cardiovascular, gastrointestinal systems to various oral mucosal alterations [1]. As a result, Tobacco smoking is one of the most significant risk factors for the occurrence of oral mucosal pre-cancerous and cancerous lesions [2]. ...
Background: Tobacco smoking is considered as one of the most common risk factors for development of oral mucosal lesions which may carry a potential risk for development of oral cancer. Objective: To find the prevalence of nicotinic stomatitis in a sample of cigarette and water pipe smokers in Erbil city of Iraq. Patients and Methods: This study included 410 smokers aged 18 years and above who are smoking for at least five years. Cigarette, water pipe and dual smokers were included of both genders. The type, duration and frequency of habit were recorded. The diagnosis of nicotinic stomatitis was done clinically. The data entered and analyzed by (SPSS software 25th version). Results: Majority of participants were cigarette smokers (73.7%).Out of 410 smoker, prevalence of nicotinic stomatitis was (55.3%) in cigarette smokers,(24.6%) in dual smokers while none of water pipe users developed nicotinic stomatitis ;the incidence increase with increase in duration and frequency of the habit. Conclusion: In this study we found cigarette smoking was more commonly practiced than water pipe .Nicotinic stomatitis is more prevalent in cigarette smoking and its incidence increased with duration and frequency of the habit.
... The amount of nicotine in 8-10 chews/dips per day is equivalent to 30-40 cigarettes per day 8 . Studies from North America, Sweden, and South Asia have linked smokeless tobacco use with pancreatic cancer, oral cancer, cardiovascular, and other diseases [9][10][11][12] . Swedish snus, a steam-pasteurized form of tobacco, contains a lower amount of nitrosamine than traditional products and has been promoted as a potential harm-reduction product. ...
Tobacco use has detrimental effects on health, including oral health. The
emergence and increasing popularity of newer tobacco and nicotine products
make tobacco use one of the major public health problems in the world.
Tobacco use increases the risk of oral diseases such as oral cancer, oral mucosal
lesions, periodontal disease, and dental caries, among many other oral diseases
and conditions. The dental office is an excellent venue for providing cessation
intervention. However, there is a lack of knowledge and training in tobacco use
prevention among dental professionals. More efforts are needed for smoking
cessation interventions in the dental office. Smoking cessation interventions
provided by oral healthcare providers include brief educational, behavioral, and
pharmacological interventions. This review provides an overview of the ill effects
of tobacco use on oral health and the role of oral healthcare providers in managing
and preventing tobacco dependence.
... The working group found no studies that reported the risk of oral cancer according to the time since the cessation of smokeless tobacco use. Six studies examined oral cancer risk in current and former users as compared with never-users: two large cohort studies in Sweden 18 and Norway 19 and four case-control studies, three in Sweden [20][21][22] and one in Yemen. 23 These studies had major limitations and minimal geographic diversity, with no studies from South Asia. ...
An expert panel review of strategies for preventing oral cancer report that the use of tobacco (both smoking and smokeless), areca nut exposure, and heavy alcohol consumption are major contributors to this illness.
... Generally, studies support a positive association between cigars and pipes and lung cancer risk [19][20][21][22] . However, the association between lung cancer and smokeless tobacco products has been inconclusive [23][24][25][26] . One possible explanation for the inconsistent results is that smokeless tobacco consists of many different forms, such as chewing tobacco, Swedish snuff, etc., and the composition of different products varies 27 . ...
Lung cancer is one of the leading causes of cancer incidence and mortality worldwide. While smoking, radon, air pollution, as well as occupational exposure to asbestos, diesel fumes, arsenic, beryllium, cadmium, chromium, nickel, and silica are well-established risk factors, many lung cancer cases cannot be explained by these known risk factors. Over the last two decades the incidence of adenocarcinoma has risen, and it now surpasses squamous cell carcinoma as the most common histologic subtype. This increase warrants new efforts to identify additional risk factors for specific lung cancer subtypes as well as a comprehensive review of current evidence from epidemiologic studies to inform future studies. Given the myriad exposures individuals experience in real-world settings, it is essential to investigate mixture effects from complex exposures and gene-environment interactions in relation to lung cancer and its subtypes.
... Most SLT products sold in the US after 1990, achieved TSNAs levels below 20 ppm as compared with generally high TSNAs levels (above 100 ppm) in earlier SLT products, sold before 1990 (67). Previous studies showed that snus had an association with an increased risk of oral or pancreatic cancer as compared with non-tobacco users (68,69). However, the current prevalence statistics and epidemiologic data on snus use, in the European population, do not indicate an increased risk of oral cancer compared with cigarettes (70). ...
Smokeless tobacco (SLT) use is a significant cause of lip and oral cavity cancers. Globally, oral cancer prevalence is strongly linked to the types of tobacco products used, their chemical composition, and their pattern of use. Except snus, all SLT products sold in different World Health Organization regions are strongly associated with oral cancer incidence. Shammah showed the highest association OR with 95% confidence intervals (CI; OR, 38.74; 95% CI, 19.50–76.96), followed by oral snuff (OR, 11.80; 95% CI, 8.45–16.49), gutkha (OR, 8.67; 95% CI, 3.59–20.93), tobacco with betel quid (OR, 7.74; 95% CI, 5.38–11.13), toombak (OR, 4.72; 95% CI, 2.88–7.73), and unspecified chewing tobacco (OR, 4.72; 95% CI, 3.13–7.11). Most SLT products containing high levels of carcinogenic tobacco-specific nitrosamines (TSNA) exhibit a high risk of oral cancer. There is an urgent need to frame and implement international policies for oral cancer prevention through legal control of the TSNA levels in all SLT product types.
Prevention Relevance
Most smokeless tobacco products sold worldwide, mainly shammah, toombak, gutkha, betel quid with tobacco, and dry snuff, are associated with a high risk of oral cancer. A high concentration of tobacco-specific nitrosamines in smokeless tobacco products is the major causative factor for oral cancer development.
... Snus is a moist tobacco product obtained by mixing tobacco-leaf powder, water, and salt (Idris et al., 1998). It has been considered an alternative to cigarettes since it is consumed through chewing, without the release of smoke and its related harmful components (Foulds et al., 2003); therefore, snus can significantly reduce the incidence of lung cancer (Luo et al., 2007). However, similar to cigarettes, snus is rich in nicotine, and the consumption of this preparation could increase the incidence of oral, pharyngeal, and pancreatic cancers, among others (Rodu, 2007). ...
In the present work, we investigated the chemical and volatile compositions of three tea-containing snus samples, after which their acceptability on the aromatic and taste coordination was evaluated by a professional panel. Results showed that the tea-containing snus samples exhibited better acceptability on the aroma and taste coordination profiles. Dahongpao tea (DT)-containing snus (DT-snus) exhibited the best acceptability of aromatic coordination, whereas the most favourable taste coordination was exhibited by Keemun black tea (KBT)-containing snus (KBT-snus). The antioxidant activity determined by the DPPH and ABTS assays revealed that Lu’an Guapian tea (LGT)-containing snus (LGT-snus) exhibited the highest free-radical scavenging ability. LGT-snus was also found to have the highest content of total polyphenols, amino acids, and caffeine. The highest levels of total flavonoids and soluble sugars were found in DT-snus and KBT-snus, respectively. There were 88, 68, and 74 volatiles found in DT-snus, LGT-snus, and KBT-snus, respectively, among which, nitrogenous compounds constituted the major category. High levels of nicotine, megastigmatrienone, neophytadiene, nicotyrine, and cotinine, which are the major volatiles in snus, were detected in the tea-containing snus samples. The mixing of tea introduced the flavour profiles of the volatiles present in the original tea into the tea-containing snus samples. Benzaldehyde, β-ionone, hexanoic acid, 3-(Z)-hexenyl ester, pyrazines, and nerolidol from LGT; furfural, benzeneethanol, nerolidol, linalool, and cedrol from DT; and nonanal, geraniol, cis-jasmone, benzenemethanol, and methyl salicylate from KBT were found in high concentrations in the corresponding tea-containing snus samples.
... A Swedish study found that use of ST (snus) was associated both with lower daily cigarette consumption among current smokers and with an increased probability of quitting smoking (Gilljam and Galanti, 2003). ST might therefore act as a marker of reduced cigarette consumption, potentially resulting in reduced, or spurious negative associations between ST use and lung cancer (Luo et al., 2007). In the current study, the pooled analysis of all studies of ST use in all subjects did not find a significant association with lung cancer risk, but the association was strengthened and became significant on restricting the analysis to studies of non-smokers. ...
Background:
Smokeless tobacco and waterpipes are used by hundreds of millions of people worldwide and consumption rates exceed that of cigarette smoking in much of South East Asia and parts of the Middle East. However, the cancer risks of these methods of tobacco consumption are less well-characterized than those of cigarette smoking. The objective of this study was to systematically review the epidemiological evidence on the association between smokeless tobacco use and waterpipe smoking and lung cancer risk.
Methods:
The MEDLINE, EMBASE, Web of Science and OpenSIGLE databases were searched to identify eligible case-control and cohort studies (published before 1st December 2020 in any language) that adjusted for cigarette smoking or included non-cigarette smokers only. Summary odds ratio/relative risk estimates and confidence intervals were extracted, and pooled risk ratios (RRs) for lung cancer were calculated using random effects meta-analysis.
Results:
The literature search identified 2,465 publications: of these, 26 studies including 6,903 lung cancer patients were included in the synthesis (20 studies of smokeless tobacco use, five of waterpipe smoking, one of both). Our results suggest that smokeless tobacco use is associated with an increased risk of lung cancer among non-cigarette smokers, and that betel quid tobacco may be particularly hazardous. The random effects meta-analysis showed that exclusive use of any type of smokeless tobacco (pooled RR = 1.53, 95%CI 1.09 - 2.14), betel quid chewing (pooled RR = 1.77, 95%CI 1.06 - 2.95), and waterpipe smoking (pooled RR = 3.25, 95%CI 2.01 - 5.25) were significantly associated with an increased risk of lung cancer.
Conclusions:
This meta-analysis of case-control/cohort studies supports the hypothesis that use of smokeless tobacco and waterpipe smoking is associated with increased risk of developing lung cancer. Considering the widespread and increasing use of smokeless tobacco in developing countries, and increasing prevalence of waterpipe smoking in almost all societies, these findings inform formulation of public health policy, legislation and tobacco control measures at national and international level to increase awareness and decrease the prevalence of smokeless tobacco use and waterpipe smoking.
... Cigarette smoking is highly addictive, widely prevalent, and very hazardous (4). Researchers have established a strong association between cigarette smoking and an increased risk of heart disease, stroke, lung cancer, and oral cancer (5)(6)(7)(8). Smoking is estimated to have killed 100 million people worldwide in the 20th century (4). Cigarette smoking may also be an important factor influencing the risk of seizures or epilepsy (9). ...
Purpose
This study aims to answer the following questions: how many people with epilepsy (PWE) have cigarette smoking habits? Which demographic or clinical characteristics are associated with cigarette smoking? Is cigarette smoking related to depressive and anxiety symptoms in PWE?
Methods
A total of 524 PWE were included in the final analysis. Demographic and clinical data were gathered and recorded. Smoking status was identified. The associations of smoking status with the clinical features of epilepsy and depressive and anxiety symptoms were evaluated by logistic regression models.
Results
The overall prevalence of cigarette smoking was 23.5% (123 PWE) in this sample. In the multivariate logistic regression model, men (adjusted OR = 10.414, 95% CI: 5.552–19.535, P < 0.001), high seizure frequency (adjusted OR = 1.474, 95% CI: 1.043–2.084, P = 0.028), and anxiety symptoms (adjusted OR = 2.473, 95% CI: 1.483–4.112, P = 0.001) were shown to have independent associations with cigarette smoking in PWE.
Conclusion
Our findings suggested that the overall prevalence of cigarette smoking was 23.5% in adults with epilepsy, which is slightly lower than that (26.6%) in general adults in China. In the present study, cigarette smoking was associated with men, high seizure frequency, and anxiety symptoms in PWE. Further prospective clinical studies with larger sample sizes are required to confirm our findings.
... However, we know that nicotine has several harmful effects on health 27 ; snus use has been associated with cardiovascular and gastrointestinal diseases, impaired or strained blood circulation, type 2 diabetes, prostate and gastrointestinal cancer, and negative impacts on reproductive health. [28][29][30][31][32][33][34][35][36][37][38] In addition, the severity of leucoplakia lesions in oral mucosa increases with the duration of snus use. 9 Snus is likely to cause strong nicotine addiction, even after shortterm use. ...
ABSTRACT Objective The health hazards of tobacco products depend on the level of exposure, but little is known about the characteristics of snus use. The aim of this study was to investigate the duration of daily exposure to snus among occasional and daily users and its associated predictive factors among young Finnish men. Design Cross-sectional questionnaire study. Setting Three out of 16 Finnish Defence Forces units. Participants 1280 young Finnish male conscripts starting their military service in 2016 chosen by simple random sampling. Primary and secondary measures The prevalence, duration of use and the amount of daily usage of snus and cigarettes were investigated. The attitudes towards perceived harmfulness of snus and the predictive factors affecting the total time of snus consumption were examined. Results Almost a fifth (19.5%) of the conscripts reported daily snus use, and a further 16% reported occasional use. Daily snus use was associated with an earlier starting age, longer duration of use and higher daily exposure time compared with occasional use. On average, daily snus users consumed 10 portions and occasional users three portions per day (p<0.001). The daily total exposure time for daily users was 372 min (95% CI 344 to 401) and for occasional users 139 min (95% CI 106 to 171). Respondents with an upper secondary education had significantly less daily total exposure than those with basic comprehensive education (p=0.036). Perceptions of snus as a harmful substance resulted in a significantly lower duration of exposure. Conclusion Snus use was very common among young Finnish men. High snus exposure duration was associated with an earlier starting age, a longer history of use and a careless attitude to its health hazards. A higher education level was a protective factor for total exposure time. Studies of the long-term health effects and dependency profile of snus use are needed.
... However, we know that nicotine has several harmful effects on health 27 ; snus use has been associated with cardiovascular and gastrointestinal diseases, impaired or strained blood circulation, type 2 diabetes, prostate and gastrointestinal cancer, and negative impacts on reproductive health. [28][29][30][31][32][33][34][35][36][37][38] In addition, the severity of leucoplakia lesions in oral mucosa increases with the duration of snus use. 9 Snus is likely to cause strong nicotine addiction, even after shortterm use. ...
Objective
The health hazards of tobacco products depend on the level of exposure, but little is known about the characteristics of snus use. The aim of this study was to investigate the duration of daily exposure to snus among occasional and daily users and its associated predictive factors among young Finnish men.
Design
Cross-sectional questionnaire study.
Setting
Three out of 16 Finnish Defence Forces units.
Participants
1280 young Finnish male conscripts starting their military service in 2016 chosen by simple random sampling.
Primary and secondary measures
The prevalence, duration of use and the amount of daily usage of snus and cigarettes were investigated. The attitudes towards perceived harmfulness of snus and the predictive factors affecting the total time of snus consumption were examined.
Results
Almost a fifth (19.5%) of the conscripts reported daily snus use, and a further 16% reported occasional use. Daily snus use was associated with an earlier starting age, longer duration of use and higher daily exposure time compared with occasional use. On average, daily snus users consumed 10 portions and occasional users three portions per day (p<0.001). The daily total exposure time for daily users was 372 min (95% CI 344 to 401) and for occasional users 139 min (95% CI 106 to 171). Respondents with an upper secondary education had significantly less daily total exposure than those with basic comprehensive education (p=0.036). Perceptions of snus as a harmful substance resulted in a significantly lower duration of exposure.
Conclusion
Snus use was very common among young Finnish men. High snus exposure duration was associated with an earlier starting age, a longer history of use and a careless attitude to its health hazards. A higher education level was a protective factor for total exposure time. Studies of the long-term health effects and dependency profile of snus use are needed.
... In some European countries like Sweden, use of smokeless tobacco in form of snuff is becoming increasingly popular. 2 Different types of smokeless tobacco with their ingredients and areas of use are shown in Table-I. Smokeless tobacco is addictive as well as harmful to health as mentioned in a 1986 report by US Surgeon General. 3 A large case-control study, INTERHEART, carried out in 52 countries established that the use of smokeless tobacco in oral and other forms is associated with high risk of cardiovascular diseases. ...
Objectives: To explore what naswar (smokeless tobacco) users know aboutthe effects of naswar on their oral and general health. Methods: This cross sectional surveywas undertaken in the city of Peshawar, Pakistan. Sample size of 96 participants based on 95%C.I with interval width of 10% was used for this study. Only male naswar users were included.Keeping in mind the resources and time constraints the participants were purposely sampled.All the participants were consented before being included in the sample. Survey tool whichincluded open, closed and semi structured questions was self-administered. Findings: 42.7%(95% CI: 32.8-52.6%) of the respondents considered naswar, either harmless or resultingin minor side effects. There was lack of awareness of the existence of oral and lung canceramong a significant proportion (41% with 95% CI: 31.8-58.5%) of participants. In response toa question about harmful effects of naswar use, vast majority of the respondents mentionedone or the other form of oral (non serious) or tooth problems. Only 10.41% (95%CI: 4.3-16.5%)mentioned its association with cancer and none mentioned about the risk of cardiovasculardisease. Conclusion: Our survey appears to indicate that level of awareness of naswar usersin Peshawar is poor. We recommend to the government of NWFP to make an effort to educatethe people about the harmful effects of naswar use.
... Thereafter, 47 studies were excluded for the following reasons: effect estimates were only provided for men and women combined (n = 19), other exposures were investigated (n = 17), or insufficient data (n = 11). Finally, 19 studies were selected for the meta-analysis [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] (Fig. 1). ...
Background
The impact of smokeless tobacco (SLT) use on the risk of oral cavity cancer (OCC) has been confirmed; however, the sex-based difference in this association remains inconclusive. Therefore, this study aimed to estimate the association between SLT use and OCC risk in women and compared it to that in men.
Methods
PubMed, Embase, and Cochrane Library databases were systematically searched for eligible studies from their inception up to August 2020. Studies reporting the effect estimates of SLT use on OCC risk in men and women, were eligible for inclusion. The relative risk ratio (RRR) was applied to calculate the sex-based difference in the relationship between SLT use and OCC risk, and pooled analysis was conducted using a random-effects model with inverse variance weighting.
Results
Nineteen studies reporting a total of 6593 OCC cases were included in the final meta-analysis. The pooled relative risk (RR) suggested that SLT use was associated with an increased risk of OCC in both men (RR, 2.94; 95% confidence interval [CI], 2.05–4.20; P < 0.001) and women (RR, 6.39; 95%CI, 3.16–12.93; P < 0.001). Moreover, the SLT-use-related risk of OCC was higher in women than that in men (RRR,1.79; 95%C, 1.21–2.64; P = 0.003). The risk of OCC related to SLT use in women was still significantly higher than that in men (RRR, 1.75; 95%CI, 1.15–2.66; P = 0.008) after excluding indirect comparison results. Finally, a subgroup analysis suggested significant sex-based differences only in individuals who received chewed smokeless products, regardless of the control definition. Pooled analysis of studies with high design quality confirmed the notably higher risk of OCC in women than in men.
Conclusions
This study found that SLT use was associated with a higher risk of OCC in women than in men. Further large-scale prospective cohort studies should be conducted to verify sex-based differences in the association between use of specific smokeless products and OCC risk.
... Numerous articles have investigated the epidemiological links between differing types of cancer and use of snus (along with other oral tobaccos) again with equivocal results. It is beyond the scope of this article to fully review this literature, however, Cancer Research UK suggests that despite the evidence being equivocal, snus has been linked to some types of cancer, particularly pancreatic cancer (Luo et al., 2007;Araghi et al., 2017) and therefore its use should be discouraged. In addition to its proposed carcinogenetic properties, the use of snus may be detrimental to cardiovascular health (Isomaa et al., 2001;Norberg et al., 2006;Reaven, 1988) with an increased risk of type- (Crystal et al., 1981;Kaijser & Berglund, 1985), and impaired endothelial function (Neunteufl et al., 2002;Rohani & Agewall, 2004). ...
The elite sport environment is one where athletes strive to find a competitive edge, through improved recovery modalities, cognitive performance or physical capacity. Due to this, non-scientifically evidenced and/or pseudo-scientific alternative remedies are ever popular. Snus (an oral tobacco based product containing the highly addictive compound nicotine) is one alternative ‘physical and psychological performance enhancer’, purported to act as a ‘mental and physical booster’, ‘relaxative’ and even as an ‘appetite suppressor’. Despite snus having serious adverse health effects, along with no proven benefit to physical or mental performance, observations by the authors working in professional sport, along with several reports in the mainstream media, would suggest that the use of snus in elite sport appears to be increasing. Perhaps most worrying, the use of snus has been reported to be prevalent within younger athletes. It is crucial that athletes are fully educated with regards to the health implications of snus and other oral tobacco-based products, whilst practitioners should be aware of its growing prevalence in sport with strategies in place to discourage its use.
... Flere av befolkningsstudiene vi vurderte, var i utgangspunktet ikke planlagt for å studere effekter av snus. I kohorten med størst antall deltagere ble snusbruk registrert sammen med en rekke andre livsstilsfaktorer, og analysene ble oftest basert utelukkende på første registrering(3). Mange deltagere kan ha slu et med snus i løpet av oppfølgingsperioden, slik det er vist i studier med gjenta e registreringer av snusbruk. ...
... One example concerns pancreatic cancer. In a study from 2007, Luo et al. investigated a cohort of Swedish construction workers who had been followed up for a period of up to 27 years (3). With close to 280,000 participating men, this is the largest available Swedish cohort with registered snus habits. ...
... Around this time, the harm reducing effects of snus (smokeless tobacco with lower levels of tobacco-specific nitrosamines, TSNAs, and other toxicants) in Sweden were being published. In past and current years, Swedish snus has been demonstrated to have a lower risk for some cancers (Luo et al., 2007;Lee and Hamling, 2009;Boffetta et al., 2008;Clarke et al., 2019), non-fatal cardiovascular disease (Clarke et al., 2019;Lee, 2007;Lee, 2011;Boffetta and Straif, 2009;Rostron et al., 2018) and pulmonary disease (Roosaar et al., 2008) than cigarettes. Among Swedish males, the increase in uptake of snus was associated with decrease in smoking concurrently with a decrease in rates of lung cancer and myocardial infarction (Foulds et al., 2003). ...
Tobacco harm reduction remains a controversial topic in tobacco control. Tobacco harm reduction involves providing tobacco users who are unwilling or unable to quit using nicotine products with less harmful nicotine-containing products for continued use. The skepticism towards harm reduction is based in part on the experience with low-yield tar/nicotine cigarettes, which were presumed to be associated with lower health risks than higher yield cigarettes and marketed as such by cigarette manufacturers. Only later did the field learn that these cigarettes were a deceptive way for cigarette manufacturers to allay the health concerns over cigarette smoking. Since this experience, there has been a proliferation of tobacco products that might potentially serve as a means to reduce tobacco harm. Some members of the tobacco control community believe that these products have great potential to reduce mortality and morbidity among smokers who completely switch to them. Others believe that we will be addicting another generation to tobacco products. This paper reviews the past history, the current tobacco landscape and controversies, and an approach that might rapidly reduce the yearly half-million deaths associated with cigarette smoking in the U.S.
... The reduction of risk is a clinical strategy widely used in drug addiction [11], but still faces obstacles in nicotine addiction. In this regard, there are interesting observations from Scandinavian countries on the use of snus in relation to cigarette combustion smoke and its link to lung cancer [12], which highlight that a direct correlation between the use of snus and lung cancer does not exist, contrary to what has been established by now regarding conventional cigarette consumption. There is still a spirited ongoing scientific debate on e-cigarettes: research has offered contradictory points in relation to e-cigarette smoking, and the media has often released information that has confused the general public. ...
... SLT use increases the risk of multiple cancers, oral diseases, as well as cardiovascular disease [6][7][8]. The health risks associated with SLT are believed to be lower than the ones associated with conventional cigarettes [9] and experts estimate that low nitrosamine SLT products including snus are 90% less harmful than conventional cigarettes [10]. However, research has found that the nicotine levels of MST products increased over time for several brands making them potentially more dangerous. ...
Background:
Little is known about how policies and industry activities impact smokeless tobacco demand. We examined how tobacco control policies and retail promotion may affect smokeless tobacco sales.
Methods:
We used Nielsen market-level retail scanner data for smokeless tobacco sales in convenience stores in 30 US regions from 2005 to 2010. Tobacco policy variables, including excise taxes, state tobacco control program expenditures, and clean indoor air laws, were merged to Nielsen markets. We estimated regression models for per capita unit sales.
Results:
Higher cigarette tax was significantly associated with lower sales volume of smokeless tobacco. Sales of smokeless tobacco in markets with a weight-based SLT excise tax were higher than in markets with an ad valorem tax. A higher average product price was associated with decreased sales overall but results varied by package quantity and brand.
Conclusions:
This study observed that smokeless tobacco products were both complements and substitutes to cigarettes. Thus, smokeless tobacco may act as complements for some population segments and substitutes for others. A weight-based tax generally favors premium smokeless tobacco products.
... Nuuskaa käyttävien riski sairastua suu tai nielusyöpään on tupakkaa käyttämättö miin verrattuna tilastollisesti merkitsevästi suu rentunut (riskisuhde 3,1), samoin riski sairastua ruokatorvi ja mahasyöpiin (riskisuhteet 3,5 ja 1,4) (31,32). Aikaisemmin osoitettua yhteyttä haimasyöpään ei useiden aineistojen yhteisana lyysissä enää havaittu (33)(34)(35). Nuuskasta saa tava nikotiini häiritsee valtimoiden seinämien normaalia toimintaa ja aiheuttaa niiden spastista supistumista. Nuuskan on myös osoitettu lisää vän tyypin 2 diabeteksen riskiä (36). ...
[Use, determinants and health risks of alternative nicotine products among youth]
In recent years, the availability of diverse tobacco and nicotine products has grown considerably. Cigarette smoking among youth decreases both in Finland and internationally, but alternative sources of nicotine, such as electronic cigarettes and snus, have grown in popularity. Experimentation with these alternative tobacco or nicotine products (ATNP) has increased among youth, but in Finland regular use has remained rare. The majority of youth experimenting with ATNPs are current smokers, but some international studies indicate increase in experimentation also among never-smoking youth. The risk factors for electronic cigarette use seem to resemble most those of cigarette smoking, but snus and waterpipe seem to appeal partly to different adolescents. Dual use, or poly-tobacco use, seems to be a growing phenomenon in youth populations. Taking into account the interactions and transmissions between the products is essential in the evaluation of the health effects of ATNPs.
Background
Tobacco use has been identified as a risk factor for oral cancer worldwide. However, relative oral cancer incidence among adults who smoke cigarettes, use smokeless tobacco products (ST), have transitioned from cigarettes to ST, quit cigarettes and/or ST (“quitters”), or never used tobacco has not been well studied.
Objective
We aim to present population-based oral cancer incidence rates for adults who smoke cigarettes, use ST, are former smokers who now use ST, or quit.
Methods
We estimated cross-sectional incidence rates and incidence rate ratios (IRRs) using data from statewide cancer registries (Colorado, Florida, North Carolina, and Texas) and population counts derived from national surveys using combined data from 2014‐2017. A random-effect meta-analysis approach was used to summarize estimates among these groups, based on multiple imputation-based IRR estimates by state and age group while considering potential heterogeneity.
Results
A total of 19,536 oral cancer cases were identified among adult males 35 years and older in the study geographies and period. The oral cancer incidence rate among adults who smoke was significantly higher than the ST group (2.6 times higher, 95% CI 2.0‐3.3, P <.001), 3.6 (95% CI 3.2‐4.1, P <.001) times higher than the never users, and 2.4 (95% CI 1.8‐3.1, P <.001) times higher compared to former smokers who now use ST. The IRR among the ST group relative to never users was 1.4 (95% CI 1.1‐1.9, P= .02). The IRR between former smokers who now use ST and those who quit was 1.4 (95% CI 1.0‐2.1, P= .08).
Conclusions
Findings from this population-based study with a large number of oral cancer cases support significantly high oral cancer incidence among adults who smoke and a lower risk of oral cancer incidence among never users, quitters, users of ST, and former smokers who now use ST compared to cigarettes. Future studies with detailed control of tobacco history and other relevant confounders are needed to confirm these findings.
This paper highlights the alarming trend of increasing nicotine use among young athletes and the role of paediatric dentists in early detection and education. Based on a presentation at the spring conference of the German Society of Paediatric Dentistry (Deutsche Gesellschaft für Kinderzahnmedizin, DGKiZ), the interface between sports dentistry and paediatric dentistry was highlighted. The tobacco industry's “harm reduction argument” will be critically examined and practical approaches for dental practice will be discussed, including sports-specific patient medical histories, preventive measures, interdisciplinary collaboration, and the importance of role models. A special focus is placed on educating patients and parents about the risks of using nicotine products.
Nicotine is highly addictive plant derived alkaloid and the most important species in human use today is Nicotiana tabacum. There are direct health effects of chronic nicotine exposure. Even in low doses, nicotine causes vasoconstriction and other cardiovascular effects related to catecholamine release and promote angiogenesis, neuroteratogenicity, and possibly some cancers¹. Periodontal disease and dental cavities and have up to 48 times the risk of oropharyngeal cancers compared with people who do not use tobacco products². Low doses exposure produces fine tremor, cutaneous vasoconstriction, increased GI motility, and increase in heart rate, respiratory rate and blood pressure³. Low dose nicotine also increases mental alertness and produces euphoria and desired psychoactive effects³. Metabolism is via the hepatic cytochrome oxidase system. The half life of nicotine in the body is 1 to 4 hours and decreases with repeated nicotine exposure4.
Background:
Contact allergy to the mint-tasting flavour carvone has been observed in patients with oral lichenoid lesions (OLL). Mint-flavoured products such as toothpaste frequently contain carvone. Snuff is a smokeless tobacco product that is chewed or placed in the mouth rather than smoked. In Sweden, the use of snuff and its flavoured versions is extremely common.
Objectives:
To investigate whether the consumption of mint-flavoured snuff is associated with contact allergy to carvone and subsequently plays a role in the aetiology of OLL.
Methods:
Regarding the two patients, patch testing with snuff pouches was performed. High-performance liquid chromatography and gas chromatography-mass spectrometry analysis were used for identification of carvone in different snuff samples.
Results:
Two patients with OLL were contacted allergic to carvone when patch tested. Both were using mint-flavoured snuffs several hours a day for many years. One patient was contacted allergic to the snuff pouch tested as is. Carvone was detected in the snuff samples of both patients.
Conclusions:
The patients were recommended to avoid the use of mint-flavoured snuffs, toothpaste and foodstuffs. At follow-up 3 months later, the patients had a dramatic clinical improvement of the OLL and oral symptoms. Exposure to mint-flavoured snuffs can be overlooked as a possible aggravating/provoking factor in OLL.
Background: This investigation provides an updated study measuring the levels of chemical components for the top-selling smokeless tobacco products (SLT) viz. khaini, mishri, pan masala + tobacco, snus, and tobacco-betel nut mixture in the Indian market.
Methods:A total of twelve SLT were collected and analyzed for nitrosamines and polycyclic aromatic hydrocarbons using various standard techniques of gas and liquid chromatography(as GC-MS, GC-TEA, LC-MS/MS)at two different laboratories and compared to previous studies.
Results: Mishri contains a major share of tobacco-specific nitrosaminesas NNN (10 folds where folds refer to a comparison of average) and NNK (25-30 folds) with higher ratio than other SLT. Total polycyclic aromatic hydrocarbons content of mishri quantified to be 702-794 µg/g of SLT which was 7-9 fold higher than snus. On geographical distribution, SLT composition reflects inter and intra-differences. TSNA levels were drastically different between mishri and khaini samples. This extensive variation is attributed to tobacco curing and other manufacturing techniques.
Conclusions: Overall, findings indicate mishri to be most harmful among all SLT whereas snus can be considered as an alternative for better public health.The chemical characterization provides a broader understanding of differences in carcinogenic-potential relating to the concentration-variation between the products. Also, the present study would create a database to ensure the consumer's right to be informed about health-risk from a product and make aware of the need to monitor and regulate the ingredients among all SLT used in the country.
Smoking continues to be the leading cause of preventable death in the United States, responsible for about one of every five deaths. Worldwide, 1 billion men and 250 million women use tobacco products. Nicotine, the primary psychoactive and addictive chemical in tobacco, drives tobacco use, leading to serious health consequences including the death of half of all long-term smokers. Given the burden smoking-related mortality/morbidity poses worldwide, policies and treatment are necessary. This article reviews tobacco use, nicotine addiction, pharmacology/biochemistry, health consequences of smoking, including a focus on vulnerable groups, and newer topics in the areas of smoking, tobacco, and nicotine delivery.
Smokeless tobacco (ST) products are used worldwide, and consumption is increasing in the United States. Although ST products are considered to occupy a different position on the tobacco product continuum of risk compared to combusted tobacco products, they can still lead to health problems, including cancer, dental problems, and changes in heart rate and blood pressure. Therefore, the determination of harmful and potentially harmful constituents (HPHCs) released from ST products into human saliva is important. Four certified reference ST products were tested in this study: loose leaf chewing tobacco (3S1), Swedish-style snus (1S4), snus (1S5), and moist snuff (3S3). These certified reference ST products are manufactured for research purposes, not for human consumption. The reference ST products were used in this study because they have been well characterized and are intended and designed to represent commercial ST products. The reference ST products were incubated in human saliva at 37 °C with a range of incubation times for the evaluation of constituents released from these products into human saliva. In this study, alkaloids (nicotine and cotinine), tobacco-specific N-nitrosamines (TSNAs) (NNN and NNK), and benzo[α]pyrene (B[α]P) in the reference ST products and saliva samples were determined by GC-MS, GC-FID, or UPLC-MS-MS. Our results indicate that the amounts of each constituent released from the reference ST products were altered by the tobacco cut size and product format (pouched or unpouched). The constituents (TSNAs and alkaloids) in moist snuff and loose leaf chewing tobacco were released faster compared to those in Swedish-style snus and snus. B[α]P was only detected in reference moist snuff samples, and only 3.4% of the total B[α]P was released into human saliva after incubation for 60 min, whereas higher percentages of total TSNAs and alkaloids were released at different rates from the four reference ST products.
This review outlines the important oral implications of tobacco use. The lining of the mouth (oral mucosa), if exposed to tobacco and its products in a susceptible individual, can develop benign, potentially malignant, and malignant tumours. Treatment and prognosis depend on tumour type, how early it is detected, its size and site in the oral cavity and whether it has spread. Advanced oral squamous cell carcinoma (OSCC) has a 20% 5‐year survival rate. Tobacco use also increases the risk of periodontitis, peri‐implantitis, caries, alveolar osteitis and halitosis. While less life threatening than OSCC, these tobacco related conditions create a substantial financial and health burden for individuals and society. Dental practitioners routinely examine the oral cavity for signs of mucosal and tooth changes, are experienced in recognising variations from normal and have established management and referral pathways. They are also ideally positioned to provide brief interventions to assist their patients to quit smoking.
Smokers are exposed to the harmful and potentially harmful constituents generated by cigarette combustion. Discriminating the independent effects of nicotine from those of other chemicals present in cigarette smoke is difficult. Nevertheless, investigating circumstances in which individuals are exposed to nicotine without combustion—as with the use of smokeless tobacco products, nicotine replacement therapies, and, to some extent, e-vapor products—provides evidence on the possible health effects of nicotine. Where epidemiological data are lacking, nonclinical studies may provide mechanistic insights into nicotine's ability to modulate molecular and cellular processes. This chapter summarizes the current knowledge about the effects of nicotine exposure on the circulatory system, lungs, female and male reproductive organs, and developing fetus and critically reviews nicotine's potential involvement in cardiovascular diseases, lung cancer, and developmental defects. This chapter also highlights key gaps in our current understanding of the biological effects of nicotine.
Background: Nicotine products have been the subject of considerable innovation over the past few decades. While the health risks of combustible cigarettes and most tobacco-based products are well characterized, there is less clarity regarding newer nicotine products, and how they compare with the traditional forms.
Methods: In this study, we have developed a relative risk hierarchy (RRH) of 13 nicotine products based on systematic review of the scientific literature and analysis of the best available evidence. In total, 3980 publications were identified and screened, with 320 studies being carried through to the final analysis. The health risk data for each product was extracted and the level assessed. The products were analyzed in terms of their toxin emissions and epidemiological data, which were combined on an arbitrary scale from 0 to 100 (low to high risk) to derive a combined risk score for each nicotine product.
Results: Combustible tobacco products dominate the top of the RRH, with combined risk scores ranging from 40 to 100. The most frequently consumed products generally score highest. Dipping and chewing tobacco place considerably lower on the hierarchy than the combustible products with scores of 10 to 15, but significantly above heat-not-burn devices and snus, which score between 3 and 4. The lowest risk products have scores of less than 0.25 and include electronic cigarettes, non-tobacco pouches and nicotine replacement therapy.
Conclusions: The RRH provides a framework for the assessment of relative risk across all categories of nicotine products based on the best available evidence regarding their toxin emissions and the observed risk of disease development in product users. As nicotine products continue to evolve, and more data comes to light, the analyses can be updated to represent the best available scientific evidence.
Background:
Smokeless tobacco (ST) is consumed by more than 300 million people worldwide. The distribution, determinants and health risks of ST differ from that of smoking; hence, there is a need to highlight its distinct health impact. We present the latest estimates of the global burden of disease due to ST use.
Methods:
The ST-related disease burden was estimated for all countries reporting its use among adults. Using systematic searches, we first identified country-specific prevalence of ST use in men and women. We then revised our previously published disease risk estimates for oral, pharyngeal and oesophageal cancers and cardiovascular diseases by updating our systematic reviews and meta-analyses of observational studies. The updated country-specific prevalence of ST and disease risk estimates, including data up to 2019, allowed us to revise the population attributable fraction (PAF) for ST for each country. Finally, we estimated the disease burden attributable to ST for each country as a proportion of the DALYs lost and deaths reported in the 2017 Global Burden of Disease study.
Results:
ST use in adults was reported in 127 countries; the highest rates of consumption were in South and Southeast Asia. The risk estimates for cancers were also highest in this region. In 2017, at least 2.5 million DALYs and 90,791 lives were lost across the globe due to oral, pharyngeal and oesophageal cancers that can be attributed to ST. Based on risk estimates obtained from the INTERHEART study, over 6 million DALYs and 258,006 lives were lost from ischaemic heart disease that can be attributed to ST. Three-quarters of the ST-related disease burden was among men. Geographically, > 85% of the ST-related burden was in South and Southeast Asia, India accounting for 70%, Pakistan for 7% and Bangladesh for 5% DALYs lost.
Conclusions:
ST is used across the globe and poses a major public health threat predominantly in South and Southeast Asia. While our disease risk estimates are based on a limited evidence of modest quality, the likely ST-related disease burden is substantial. In high-burden countries, ST use needs to be regulated through comprehensive implementation of the World Health Organization Framework Convention for Tobacco Control.
The present report is prepared in accordance with the decisions taken by the
Conference of the Parties (COP) at its sixth session in October 2014
(FCTC/COP/6/9). It provides an overview of the status of smokeless tobacco (SLT)
control policy and its implementation by the Parties to the World Health
Organization Framework Convention on Tobacco Control (WHO FCTC). Besides
facilitating an exclusive discussion on SLT policy related matters in an Inter-Party
Meeting cum Global Expert Consultation, it also provides a comparative progress
with progress indicators with cigarettes, some key observations on the progress
made in SLT control policy by Parties. It further explores opportunities and
challenges related to the specific articles under the convention along with
proposed recommendations.
The emergence of new tobacco heating products and electronic nicotine delivery systems (ENDS) is changing the way humans are exposed to nicotine. The purpose of this narrative review is to provide a broad overview of published scientific literature with respect to the effects of nicotine on three key health-related areas: 1) cardiovascular risk, 2) carcinogenesis and 3) reproductive outcomes. These areas are known to be particularly vulnerable to the effects of cigarette smoke, and in addition, nicotine has been hypothesized to play a role in disease pathogenesis. Acute toxicity will also be discussed.
The literature to February 2019 suggests that there is no increased cardiovascular risk of nicotine exposure in consumers who have no underlying cardiovascular pathology. There is scientific consensus that nicotine is not a direct or complete carcinogen, however, it remains to be established whether it plays some role in human cancer propagation and metastasis. These cancer progression pathways have been proposed in models in vitro and in transgenic rodent lines in vivo but have not been demonstrated in cases of human cancer.
Further studies are needed to determine whether nicotine is linked to decreased fertility in humans. The results from animal studies indicate that nicotine has the potential to act across many mechanisms during fetal development. More studies are needed to address questions regarding nicotine exposure in humans, and this may lead to additional guidance concerning new ENDS entering the market.
Background:
Modified risk tobacco products (MRTPs) can reduce harm by decreasing exposure to combustion-related toxicants. In the absence of epidemiological data, biomarkers of potential harm (BoPH) are useful to evaluate the harm-reducing potential of MRTPs. This study evaluated whether arachidonic acid (AA)-derived metabolites serve as short-term BoPH for predicting harm reduction in tobacco product-switching studies.
Methods:
We used 24-hr urine samples from participants in a series of short-term studies in which smokers switched from combustible to non-combustible tobacco products (oral smokeless tobacco products or electronic nicotine delivery system [ENDS]) or abstinence. Pre- and post-switching samples were analyzed by LC-MS/MS for alterations in select AA metabolites including prostaglandins, isoprostanes, thromboxanes, and leukotrienes.
Results:
Switching to abstinence, dual-use of combustible and non-combustible products, or exclusive use of non-combustible products resulted in reduced 2,3-d-TXB2 levels. Moreover, switching smokers to either abstinence or exclusive use of oral tobacco products resulted in reduced LTE4, but dual-use of combustible and oral tobacco products or ENDS did not. A two-biomarker classification model comprising 2,3-d-TXB2 and LTE4 demonstrated the highest performance in distinguishing smokers switched to either abstinence, or to ENDS and oral smokeless tobacco products.
Conclusions:
Urinary 2,3-d-TXB2 and LTE4 can discriminate between combustible tobacco users and combustible tobacco users switched to either abstinence or non-combustible products for five days.
Impact:
2,3-d-TXB2 and LTE4, which are linked to platelet activation and inflammation, represent BoPH in short-term tobacco product-switching studies. Thus, from a regulatory perspective, 2,3-d-TXB2 and LTE4 may aid in assessing the harm reduction potential of MRTPs.
The emergence of new tobacco heating products and electronic nicotine delivery systems (ENDS) is changing the way humans are exposed to nicotine. The purpose of this narrative review is to provide a broad overview of published scientific literature with respect to the effects of nicotine on three key health-related areas: 1) cardiovascular risk, 2) carcinogenesis and 3) reproductive outcomes. These areas are known to be particularly vulnerable to the effects of cigarette smoke, and in addition, nicotine has been hypothesized to play a role in disease pathogenesis. Acute toxicity will also be discussed.
The literature to February 2019 suggests that there is no increased cardiovascular risk of nicotine exposure in consumers who have no underlying cardiovascular pathology. There is scientific consensus that nicotine is not a direct or complete carcinogen, however, it remains to be established whether it plays some role in human cancer propagation and metastasis. These cancer progression pathways have been proposed in models in vitro and in transgenic rodent lines in vivo but have not been demonstrated in cases of human cancer.
Further studies are needed to determine whether nicotine is linked to decreased fertility in humans. The results from animal studies indicate that nicotine has the potential to act across many mechanisms during fetal development. More studies are needed to address questions regarding nicotine exposure in humans, and this may lead to additional guidance concerning new ENDS entering the market.
SUMMARY Background Large health care utilization databases are frequently used to analyze unintended effects of prescription drugs and biologics. Confounders that require detailed information on clinical parameters, lifestyle, or over-the-counter medications are often not measured in such datasets, causing residual confounding bias. Objective This paper provides a systematic approach to sensitivity analyses to investigate the impact of residual confounding in pharmacoepidemiologic studies that use health care utilization databases. Methods Four basic approaches to sensitivity analysis were identified: (1) sensitivity analyses based on an array of informed assumptions; (2) analyses to identify the strength of residual confounding that would be necessary to explain an observed drug-outcome association; (3) external adjustment of a drug-outcome association given additional information on single binary confounders from survey data using algebraic solutions; (4) external adjustment considering the joint dis- tribution of multiple confounders of any distribution from external sources of information using propensity score calibration. Conclusion Sensitivity analyses and external adjustments can improve our understanding of the effects of drugs and biologics in epidemiologic database studies. With the availability of easy-to-apply techniques, sensitivity analyses should be used more frequently, substituting qualitative discussions of residual confounding. Copyright # 2006 John Wiley & Sons, Ltd.
Background
Large health care utilization databases are frequently used to analyze unintended effects of prescription drugs and biologics. Confounders that require detailed information on clinical parameters, lifestyle, or over-the-counter medications are often not measured in such datasets, causing residual confounding bias.Objective
This paper provides a systematic approach to sensitivity analyses to investigate the impact of residual confounding in pharmacoepidemiologic studies that use health care utilization databases.Methods
Four basic approaches to sensitivity analysis were identified: (1) sensitivity analyses based on an array of informed assumptions; (2) analyses to identify the strength of residual confounding that would be necessary to explain an observed drug-outcome association; (3) external adjustment of a drug-outcome association given additional information on single binary confounders from survey data using algebraic solutions; (4) external adjustment considering the joint distribution of multiple confounders of any distribution from external sources of information using propensity score calibration.Conclusion
Sensitivity analyses and external adjustments can improve our understanding of the effects of drugs and biologics in epidemiologic database studies. With the availability of easy-to-apply techniques, sensitivity analyses should be used more frequently, substituting qualitative discussions of residual confounding. Copyright © 2006 John Wiley & Sons, Ltd.
Although cigarette smoking has consistently been shown to be positively related to the risk of adenomatous polyp development (benign neoplastic growth of epithelial tissue in the colon), most studies of cigarette smoking and the risk of colorectal cancer have been negative. However, in two large prospective studies in women and men, a statistically significant association between cigarette smoking and an increased risk of colorectal cancer was found, but only after more than 35 years of smoking.
To shed further light on the alleged relationship between long-term smoking and colorectal cancer risk, we performed a retrospective cohort study among Swedish construction workers, with many long-term smokers, complete long-term follow-up, and a large number of observed cases.
We analyzed the association of smoking with colon cancer and with rectal cancer, using data on a cohort of approximately 135000 male construction workers. High-quality exposure information was collected with the use of a comprehensive questionnaire filled out at the time of enrollment in the cohort, from 1971 through 1975. Complete follow-up was achieved through 1991 and the subjects were observed for an average of 17.6 years, thereby contributing approximately 2375000 person-years of follow-up. We calculated age-adjusted rate ratios (RRs) with the use of Poisson-based multiplicative multivariate models followed by further multivariate modeling that adjusted for other variables.
A total of 713 incident colon cancers and 505 rectal cancers were observed. There was no statistically significant association between current smoking status, number of cigarettes smoked or number of years smoking, and risk of colorectal cancer. The age-adjusted RRs were 0.98 (95% confidence interval [CI] = 0.82-1.17) and 1.16 (95% CI = 0.94-1.44) for colon and rectal cancers, respectively, among current smokers, and 1.07 (95% CI = 0.63-1.82) and 1.08 (95% CI = 0.58-2.03) among smokers of 25 or more cigarettes per day, relative to nonsmokers. Among smokers for more than 30 years at the start of follow-up, the age-adjusted RRs were 1.03 (95% CI = 0.85-1.25) and 1.21 (95% CI = 0.96-1.53) for colon and rectal cancers, respectively, relative to nonsmokers. Heavy smokers of cigars and pipes had a statistically nonsignificant tendency toward excess risk for colon cancer, but there was no clear dose-risk trend.
Our large cohort study did not indicate any excess risk of colon cancer in males who were long-term heavy smokers and provided only weak support for an association with rectal cancer. Our data are thus consistent with the majority of previous reports. The reasons for the discrepancies in comparison with recent U.S. data have yet to be identified.
Reports of dramatic increases in gastric cardia cancer incidence warrant concern. However, the recent introduction of a separate diagnostic code, the lack of a consensus definition of the cardia area, and the accelerating interest in cardia cancer may affect classification practices. Little is known about the magnitude of cardia cancer misclassification in large cancer registries.
In a well-defined Swedish population (1.3 million), we uniformly classified all patients with newly diagnosed gastric adenocarcinoma (from 1989 through 1994) with respect to gastric subsite, and we used this patient group as our gold standard. We then evaluated the completeness of the Swedish Cancer Registry in registering gastric adenocarcinomas against this gold standard and, further, assessed the completeness of cardia cancer registration and the rate of falsely included cases to estimate the potential impact on observed incidence trends.
Our gold standard contained 1337 case subjects with gastric adenocarcinoma. Overall, the Swedish Cancer Registry was 98% complete with regard to gastric adenocarcinomas and had a 4% rate of falsely included cases. The completeness of coding cardia cancer was only 69%, and the positive predictive value for cardia cancer was 82%, with no improvement over time.
Although overall completeness of gastric cancer registration by the Swedish Cancer Registry was excellent, accuracy in registering cardia tumors was surprisingly low. Our estimates suggest that true cardia cancer incidence could be up to 45% higher or 15% lower than that reported in the Cancer Registry. This margin of error could accommodate the observed increase in cardia cancer in Sweden. Therefore, secular trends in cardia cancer incidence should be interpreted cautiously.
South Asia is a major producer and net exporter of tobacco. Over one-third of tobacco consumed regionally is smokeless. Traditional forms like betel quid, tobacco with lime and tobacco tooth powder are commonly used and the use of new products is increasing, not only among men but also among children, teenagers, women of reproductive age, medical and dental students and in the South Asian diaspora. Smokeless tobacco users studied prospectively in India had age-adjusted relative risks for premature mortality of 1.2-1.96 (men) and 1.3 (women). Current male chewers of betel quid with tobacco in case-control studies in India had relative risks of oral cancer varying between 1.8-5.8 and relative risks for oesophageal cancer of 2.1-3.2. Oral submucous fibrosis is increasing due to the use of processed areca nut products, many containing tobacco. Pregnant women in India who used smokeless tobacco have a threefold increased risk of stillbirth and a two- to threefold increased risk of having a low birthweight infant. In recent years, several states in India have banned the sale, manufacture and storage of gutka, a smokeless tobacco product containing areca nut. In May 2003 in India, the Tobacco Products Bill 2001 was enacted to regulate the promotion and sale of all tobacco products. In two large-scale educational interventions in India, sizable proportions of tobacco users quit during 5-10 years of follow-up and incidence rates of oral leukoplakia measured in one study fell in the intervention cohort. Tobacco education must be imparted through schools, existing government health programmes and hospital outreach programmes.
Smokeless tobacco has been associated with oral cancer for many decades. The purpose of this article is to review research relevant to this association, including epidemiologic studies, studies of putative carcinogens such as tobacco-specific nitrosamines (TSNAs) and other contaminants, and possible cancer inhibitors. Epidemiologic studies addressing this issue primarily consist of case-control studies. They show that the use of chewing tobacco and moist snuff is associated with very low risks for cancers of the oral cavity and related structures (relative risks [RR] from 0.6 to 1.7). The use of dry snuff is associated with higher RRs, ranging from 4 to 13, while the RRs from smokeless tobacco, unspecified as to type, are intermediate (RR = 1.5 to 2.8). With regard to TSNAs, historical levels in American moist snuff products were higher than those in their Swedish counterparts, but levels in contemporary products are uniformly low. TSNA levels in chewing tobacco have always been low, but levels in dry snuff have been higher, including some very high levels in current products. In general, smokeless tobacco users are not exposed to significant levels of cadmium, lead, benzo(a)pyrene, polonium-210, and formaldehyde, when compared with concentrations of these compounds in foods. Finally, low oral cancer risk from smokeless tobacco use may be influenced by the presence of cancer inhibitors, mainly anti-oxidants, in smokeless tobacco products.
For decades men in Sweden have smoked at far lower rates than those in comparable countries. Previous studies showed that snus use played a major role in low smoking rates among men in northern Sweden; daily smoking declined from 19% (95% CI 16-22%) in 1986 to 11% (CI 8.9-14%) in 1999. The prevalence of smoking among all men is now 9% (CI 7.0-11%) and only 3% (CI 0.1-5.4%) among men age 25-34 years; the prevalence of exclusive snus use is 27% (CI 24-30%) and 34% (CI 27-42%) respectively. Combined smoking and snus use, an unstable and transient category, was under 5% in all surveys and was 2.2% (CI 1.4-3.4%) by 2004. For the first time snus use is also associated with a decrease in smoking prevalence among women. These patterns of tobacco use have implications for all smoking-dominated societies.
The results of this study confirm that both smoking of tobacco and alcohol consumption are risk factors for oral and oropharyngeal squamous cell carcinoma (OOSCC). The use of moist snuff had no effect on the risk of OOSCC, probably due to the low levels of tobacco-specific N-nitrosamines in Swedish moist snuff.
The aims of this population-based case-control study in southern Sweden were to establish risk estimates for cigarette and alcohol consumption and to evaluate whether Swedish moist snuff is a risk factor for OOSCC.
Between September 2000 and January 2004, 132/165 consecutive cases (80%) diagnosed with OOSCC and 320/396 matched controls (81%) were investigated. All subjects were interviewed and examined according to a standardized protocol.
Individuals who drank > or =350 g of alcohol/week showed an increased risk of OOSCC (OR 2.6; 95% CI 1.3-5.4). Total lifetime consumption of tobacco for smoking (>250 kg) had a dose-response effect on the risk of OOSCC (OR 4.7; 95% CI 2.4-9.1). We found no increased risk of OOSCC associated with the use of Swedish moist snuff (OR 1.1; 95% CI 0.5-2.5).
To study the prevalence of snus use and of smoking among Swedish schoolchildren from 1989 to 2003.
Surveys conducted by the Swedish Council for Information on Alcohol and Other Drugs.
All of Sweden.
84,472 boys and girls age 15-16 years.
Subjects are classified as non-smokers, occasional smokers, and regular smokers, and into three similar categories for snus use. Tobacco use is reported as sex specific prevalence.
During the period 1989 to 2003, the prevalence of tobacco use declined both among boys and girls. For boys, regular smoking declined after 1992 from 10% to 4%. Their snus use was about 10% in the 1990s but increased to 13% by 2003. Regular smoking among girls was 20% in early years and declined to 15%. Smoking among girls was always double that among boys. Patterns of occasional tobacco use were similar to those of regular use.
The high prevalence of snus use in Sweden not only reduces smoking rates among Swedish men, but suppresses smoking among boys as well.
From personal interviews obtained for 7,518 incident cases of invasive cancer from the population-based Third National Cancer Survey, the quantitative lifetime use of cigarettes, cigars, pipes, unsmoked tobacco, wine, beer, hard liquor, and combined alcohol were recorded, as well as education and family income level. In an initial screening analysis of these data, Mantel-Haenszel 2×2 contingency tabulations and multiple regression analyses were used to compare each specific cancer site with controls from other sites to test for associations with the “exposure variables.” Significant positive associations with cigarette smoking were found for cancers of the lung, larynx, oral cavity, esophagus, stomach, pancreas, bladder, kidney, and uterine cervix. Other forms of tobacco were associated with cancers of the oral cavity, larynx, lung, and cervix. Consumption of wine, beer, hard liquor, and all combined showed positive associations with neoplasms of the oral cavity, larynx, esophagus, colon, rectum, breast, and thyroid gland. College education and high income both showed positive associations with cancers of the breast, thyroid gland, uterine corpus, and melanomas in males. These same indicators of high socioeconomic status showed inverse associations with invasive neoplasms of the uterine cervix, lung, lip-tongue, and colon in females. College attendance (but not income) showed an inverse association with stomach cancer and positive association with pancreatic cancer in males. Still other tumor sites showed “suggestive” associations with each of these exposure variables. In the analyses producing these results, age, race, sex, smoking, drinking, education, income, parity, foreign birth, marital status, and geographic location were used as stratification variables separately or in combination when appropriate to assess and control for their potentially confounding affects and to examine results in different strata to assess interaction.
This paper presents a new class of graphical and numerical methods for checking the adequacy of the Cox regression model. The procedures are derived from cumulative sums of martingale-based residuals over follow-up time and/or covariate values. The distributions of these stochastic processes under the assumed model can be approximated by zero-mean Gaussian processes. Each observed process can then be compared, both visually and analytically, with a number of simulated realizations from the approximate null distribution. These comparisons enable the data analyst to assess objectively how unusual the observed residual patterns are. Special attention is given to checking the functional form of a covariate, the form of the link function, and the validity of the proportional hazards assumption. An omnibus test, consistent against any model misspecification, is also studied. The proposed techniques are illustrated with two real data sets.
Context Previous studies reported an increased risk of pancreatic cancer among persons with diabetes. Few data exist, however, on the association of postload plasma glucose concentration with pancreatic cancer, which could provide insight into the role of abnormal glucose metabolism in the etiology of pancreatic cancer. Objective To determine the independent association between postload plasma glucose concentration and risk of pancreatic cancer mortality among persons without self-reported diabetes. Design Prospective cohort study. Setting and Participants Employees of 84 Chicago-area organizations, with an average age of 40 years at baseline, were screened from 1963 to 1973 and followed up for an average of 25 years. A total of 96 men and 43 women died of pancreatic cancer among 20475 men and 15 183 women, respectively. Main Outcome Measures Relationship of pancreatic cancer mortality with postload plasma glucose levels. Results Compared with a postload plasma glucose level of 6.6 mmol/L (119 mg/ dL) or less and after adjusting for age, race, cigarette smoking, and body mass index, the relative risks (95% confidence intervals) of pancreatic cancer mortality were 1.65 (1.05-2.60) for postload plasma glucose levels between 6.7 (120) and 8.8 (159) mmol/L (mg/dL); 1.60 (0.95-2.70) for levels between 8.9 (160) and 11.0 (199); and 2.15 (1.22-3.80) for levels of 11.1 (200) or more; P far trend = .01. An association appeared to be stronger for men than women. Estimates were only slightly lower after excluding 11 men and 2 women who died of pancreatic cancer during the first 5 years of followup. In men only, higher body mass index and serum uric acid concentration also were independently associated with an elevated risk of pancreatic cancer mortality. Conclusion These results suggest that factors associated with abnormal glucose metabolism may play an important role in the etiology of pancreatic cancer.
The use of oral snuff is a widespread habit in Sweden. We investigated whether the use of Swedish moist snuff leads to an increasing risk of oral cancer. Other risk factors such as smoking tobacco and alcoholic beverages were also investigated. Our study comprised 410 patients with oral cancer, from the period 1980–1989, and 410 matched controls. All subjects received a mailed questionnaire. The response rates were 96% and 91% for cases and controls, respectively. In the study, a total of 20% of all subjects, cases and controls, were active or ex-snuff users. The univariate analysis did not show any increased risk [odds ratio (OR) 0.7, 95% confidence interval (CI) 0.4–1.1] for active snuff users. We found an increased risk (OR 1.8, CI 1.1–2.7) for oral cancer among active smokers. Alcohol consumption showed the strongest risk for oral cancer. Among consumers of beer, an increased risk of 1.9 (CI 0.9–3.9) was found. Corresponding ORs for wine and liquor were 1.3 (CI 0.9–1.8) and 1.6 (CI 1.1–2.3), respectively. A dose-response effect was observed. Although not statistically significant, a multivariate analysis similarly suggested that the most important risk factors were beer and liquor consumption, followed by smoking. Int. J. Cancer 77:341–346, 1998. © 1998 Wiley-Liss, Inc.
BACKGROUND
This case-referent study was conducted to elucidate the role of selected exogenous agents in the etiology of head and neck cancer. The factors studied were tobacco smoking, alcohol intake, the use of moist oral snuff, dietary factors, occupational exposures, and oral hygiene. In this first report, the authors discuss the impact of tobacco smoking, the use of oral snuff, and alcohol consumption.METHODS
The study base was approximately 2 million person-years at risk and consisted of Swedish males age 40-79 years living in 2 geographic regions during the years 1988-1990. A total of 605 cases were identified in the base, and 756 controls were selected by stratified random sampling from population registries covering the base.RESULTSAmong those who were tobacco smokers at the time of the study, the relative risk of head and neck cancer was 6.5% (95% confidence interval, 4.4-9.5%). After cessation of smoking, the risk gradually declined, and no excess risk was found after 20 years. The relative risk associated with alcohol consumption of 50 grams or more per day versus less than 10 grams per day was 5.5% (95% confidence interval, 3.1-9.6%). An almost multiplicative effect was found for tobacco smoking and alcohol consumption.CONCLUSIONS
Tobacco smoking and alcohol intake had a strong interactive effect on the risk of squamous cell carcinoma of the head and neck. Moderate alcohol intake (10-19 grams per day) had little or no effect among nonsmokers. No increased risk was found for the use of Swedish oral snuff. Cancer 1998;82:1367-75. © 1998 American Cancer Society.
In the United States, smokeless tobacco (ST) is marketed as chewing tobacco and as oral snuff. During the past 15 years, consumption of chewing tobacco has declined by 30.6%, whereas snuff use has significantly increased, namely, by 51.8%. This increase is primarily due to the growing popularity of oral snuff use among teenage and young adolescent males. Chewing of tobacco is associated with an increased risk for oral cancer. Snuff dipping is causally and specifically associated with cancer of the cheek, gum, and pharynx. In laboratory animals, snuff induces cancer of the mouth. Several carcinogens have been identified in ST, the tobacco-specific N-nitrosamine (TSNA), N'-nitrosonornicotine (NNN), and 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) being the most important. NNN and NNK are formed from nicotine during curing, aging, and especially during fermentation of tobacco. Oral swabbing of a low concentration of a mixture of NNN plus NNK in water induces oral tumors in rats. The concentration of the strongly carcinogenic TSNA is higher in snuff than in other ST products. According to our analytical studies, the three leading snuff brands in the US (92% of the market) contain far higher concentrations of nicotine, unprotonated nicotine, and TSNA than the less popular brands. Thus, the leading US snuff brands are the strongest inducers of nicotine dependence and also have the highest carcinogenic potential.
From personal interviews obtained for 7,518 incident cases of invasive cancer from the population-based Third National Cancer Survey, the quantitative lifetime use of cigarettes, cigars, pipes, unsmoked tobacco, wine, beer, hard liquor, and combined alcohol were recorded, as well as education and family income level. In an initial screening analysis of these data, Mantel-Haenszel 2 X 2 contingency tabulations and multiple regression analyses were used to compare each specific cancer site with controls from other sites to test for associations with the "exposure variables." Significant positive associations with cigarette smoking were found for cancers of the lung, larynx, oral cavity, esophagus, stomach, pancreas, bladder, kidney, and uterine cervix. Other forms of tobacco were associated with cancers of the oral cavity, larynx, lung, and cervix. Consumption of wine, beer, hard liquor, and all combined showed positive associations with neoplasms of the oral cavity larynx, esophagus, colon, rectum, breast, and thyroid gland. College educaton and high income both showed positive associations with cancers of the breast, thyroid gland, uterine corpus, and melanomas in males. These same indicators of high socioeconomic status showed inverse associations with invasive neoplasms of the uterine cervix, lung, lip-tongue, and colon in females. College attendance (but not income) showed an inverse association with stomach cancer and positive association with pancreatic cancer in males. Still other tumor sties showed "suggestive" associations with each of these exposure variables. In the analyses producing these results, age, race, sex, smoking, drinking, education, income, parity, foreign birth, marital status, and geographic location were used as stratification variables separately or in combination when appropriate to assess and control for their potentially confounding affects and to examine results in different strata to assess interaction.
The Areca-derived 3-(methylnitrosamino)propionitrile (MNPN) was tested for its tumor initiating activity on mouse skin and for its tumorigenic potential in the oral mucosa of rats. On mouse skin, like the otherwise strongly carcinogenic, tobacco-specific 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), MNPN showed only weak local tumor initiator activity. However, the application of MNPN to mouse skin led also to multiple distant tumors in the lungs of the animals. Twice daily swabbing of the oral cavity of rats with aqueous solutions of MNPN or NNK for up to 61 weeks led only to one oral tumor in each group of 30 animals. Yet, these N-nitrosamines proved again to be strong organ-specific carcinogens. Thus, MNPN induced nasal tumors in 80% of the rats and lung adenomas in 13%, liver tumors in 10% and papillomas of the esophagus in 7%. NNK induced lung adenoma and/or adenocarcinoma in 90%, nasal tumors in 43% and liver adenomas/adenocarcinomas in 30% of the rats. These results confirm previous observations that, independent of the site and mode of application, MNPN and NNK remain strong organ-specific carcinogens in laboratory animals.
A population-based case-control study was conducted to examine the relationship between certain medical conditions, the use of tobacco, alcohol and coffee, and the incidence of pancreatic cancer. Cases (N = 148) were married men ages 20 through 74 years diagnosed with pancreatic cancer from July 1982 through June 1986. Controls (N = 188) were identified by random digit dialing. Wives, responding as surrogates for both cases and controls, were interviewed by telephone and completed, alone, a food frequency questionnaire. The risk of pancreatic cancer was increased in individuals with a history of diabetes or pancreatitis, and decreased in those with a history of tonsillectomy. Individuals who had ever smoked cigarettes were at elevated risk of disease. This excess risk was confined to current smokers, in whom the odds ratio was 3.2 (95% CI 1.8-5.7); the risk among former smokers resembled that in those who had never smoked. There was no excess risk of pancreatic cancer among those who had ever used other forms of tobacco, including pipe tobacco, cigars and chewing tobacco. After adjustment for demographic and dietary characteristics, there was no association between pancreatic cancer risk and the intake of coffee, beer, red wine, hard liquor or all alcohol combined; a slight reduction in risk was seen among those consuming white wine daily.
The tobacco-specific N-nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), as well as the Areca-derived N-nitrosoguvacoline (NG) were assayed for carcinogenicity in male F344 rats by lifetime administration in the drinking water. Groups of 30 to 80 rats were treated with 0.5 ppm, 1.0 ppm, or 5.0 ppm of NNK; 5.0 ppm of NNAL, 20 ppm of NG, a mixture of 20 ppm of NG and 1 ppm of NNK, and water only in the control group. The approximate total doses of the nitrosamines (mmol/kg of body weight) in these groups were: NNK, 0.073, 0.17, and 0.68; NNAL, 0.69; NG, 4.1; NG and NNK, 4.1 and 0.17. As in previous assays in which NNK was tested by s.c. injection, the lung was its principle target organ. Lung tumor incidences in the 0.5-, 1.0-, and 5.0-ppm groups were nine of 80, 20 of 80, and 27 of 30 compared to six of 80 in the control rats. This trend was significant, P less than 0.005. Significant incidences of nasal cavity and liver tumors were observed only in the rats treated with 5.0 ppm of NNK. In contrast to the results of the s.c. bioassays of NNK, tumors of the exocrine pancreas were observed in five of 80 and nine of 80 rats treated with 0.5 and 1.0 ppm. This trend was significant, P less than 0.025. This is the first example of pancreatic tumor induction by a constituent of tobacco smoke. It is also the first finding of duct-like carcinomas in the rat pancreas, including one tumor containing epidermoid, keratin-generating tissue. NNAL, the major metabolite of NNK, induced lung tumors in 26 of 30 rats and pancreatic tumors in eight of 30 rats. It appears to be the proximate pancreatic carcinogen of NNK. NG induced pancreatic tumors in four of 30 rats, P less than 0.05. This finding requires confirmation. The mixture of NG and NNK induced lung tumors in eleven of 30 rats. There were no apparent synergistic interactions of NG and NNK. The observation of benign and malignant tumors of the lung and pancreas of rats treated with the tobacco-specific nitrosamines NNK and NNAL is discussed in respect to the causal association between cigarette smoking and cancer of the lung and pancreas.
Of the death certificates issued in Sweden in 1978 and stating cancer as the underlying or contributory cause of death, 1634 cases were unrecorded in the national cancer register. In 62 per cent of the cases the criteria for cancer registration were fulfilled. The non-reported cases represented a total deficit of 4.5 per cent calculated on cancer deaths in 1978. The factors responsible for the deficit were investigated. When the diagnosis had been histologically/cytologically confirmed the deficit was less than 2 per cent but was about 30 per cent when the diagnostic basis was only clinical. More than half of the non-notified cancer patients were older than 75 years. Exclusion of this age group and of myeloma and leukaemia cases gave a cancer-register deficit of 2.3 per cent. Non-notification to the Swedish cancer registry can be diminished by supplementation with data from death certificates, as practised in other Nordic countries. On regional basis these death certificates will now be collected and used as a supplement to the cancer notification in Sweden.
Moist snuff is the only tobacco product in the United States with increasing sales (an increase of 38.4% between 1981 and 1993) and with increased consumption, primarily by male adolescents aged 12-18 years old and young adults aged 19 years old or older. It is known from previous studies that levels of nicotine and the proportion of unprotonated (free) nicotine, as well as the pH, which affects nicotine delivery, vary considerably among the leading snuff brands. Whether concentrations of major carcinogens, such as the nicotine-derived tobacco-specific N-nitrosamines (TSNAs), like N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), also vary among these brands has not been determined previously.
Our purpose was threefold: 1) to determine the concentrations of major carcinogenic nicotine-derived N-nitrosamines in each of the five most popular moist snuff brands; 2) to analyze the quantitative differences in the various snuff components (e.g., NNN) between two major brand categories: a category comprising the brands known to have high levels of unprotonated nicotine (Copenhagen, Skoal fine cut, and Kodiak) versus a category comprising the brands known to have low levels (Hawken and Skoal Bandits); and 3) to compare the differences in the concentrations of nicotine (previously determined), NNN, NNK, and total TSNAs between these two major brand categories.
Three boxes of each of the five leading U.S. moist snuff brands were bought in July 1994 from retailers in six areas and transferred immediately to the analytical laboratory. After extraction, N-nitrosamino acids and TSNAs were determined on a gas chromatograph interfaced with a thermal energy analyzer (GC-TEA) and integrator. Each 5-g sample of ground, freeze-dried tobacco was extracted twice, and each extract was analyzed twice by GC-TEA. All P values reported are two sided.
Copenhagen, Skoal fine cut, and Kodiak as a group had statistically significant higher levels of nicotine (P = .0017), NNN (P < .0001), NNK (P = .0119), and total TSNAs (P < .0001) than the Hawken and Skoal Bandits group. Concentrations (means +/- SD) of nicotine, NNN, NNK, and total TSNAs comparing the two major brand categories are as follows: nicotine--11.6 +/- 1.01 mg/g versus 6.96 +/- 3.62 mg/g (P = .0017), NNN--7.74 +/- 1.70 micrograms/g versus 4.17 +/- 1.35 micrograms/g (P < .0001), NNK--1.23 +/- 0.68 micrograms/g versus 0.61 +/- 0.41 micrograms/g (P = .0119), and total TSNAs--14.3 +/- 3.82 micrograms/g versus 6.3 +/- 2.56 micrograms/g (P < .0001).
The three leading U.S. snuff brands (Copenhagen, Skoal fine cut, and Kodiak; making up 92% of the U.S. market) showed not only high levels of pH, nicotine, and unprotonated (free) nicotine, but also high concentrations of the strongly carcinogenic TSNAs in comparison with the fourth and fifth best selling moist snuff brands, Hawken and Skoal Bandits (3% of the U.S. market).
Risk factors for pancreatic cancer were evaluated in a cohort study of 17,633 White men in the United States who responded to a mailed questionnaire in 1966 and were followed-up through 1986 for mortality. Cigarette smoking and alcohol consumption were found to be important risk factors for pancreatic cancer. Risks increased significantly with number of cigarettes smoked, reaching fourfold for smokers of 25 or more cigarettes per day relative to nonsmokers. Alcohol intake also was related significantly to risk, with consumers of 10 or more drinks per month having three times the risk of nondrinkers, but dose-response trends among drinkers were not smooth. Coffee consumption was unrelated to risk. Dietary analyses revealed a rising rate of pancreatic cancer mortality with increasing consumption of meat after adjustment for other risk factors. Men in the highest quartile of meat intake had about three times the risk of those in the lowest quartile. No consistent association, however, was observed for consumption of fruits, vegetables, or grains. This study confirms cigarette smoking as an important risk factor for pancreatic cancer, and provides evidence that elevated intake of alcohol and meat may increase the risk of this fatal malignancy.
Most studies of smoking and pancreatic cancer have used male subjects or combined men and women together in statistical analyses. There is little information on the relative risk of smoking and pancreatic cancer in women. Because of the high case-fatality rate, many of these studies were also based on information gathered from proxy respondents, in which smoking habits may not be recalled with certainty. A hospital-based study of 484 male and female patients with pancreatic cancer and 954 control subjects was conducted based on direct interviews of incident cases. Compared to never smokers, the odds ratio (OR) for current cigarette smokers was 1.6 [95% confidence interval (CI), 1.1-2.4] for men and 2.3 (95% CI, 1.4-3.5) for women. In women, but not in men, there was a trend in the ORs with years of daily cigarette consumption (P < 0.01). Filter cigarettes offered no protective advantage compared to nonfilter cigarettes. Among men, the OR was 2.1 (95% CI, 1.2-3.8) for pipe/ cigar smokers and 3.6 (95% CI, 1.0-12.8) for tobacco chewers. Tobacco smoke causes pancreatic cancer when inhaled into the lungs. Tobacco juice may also cause pancreatic cancer when ingested or absorbed through the oral cavity. These data suggest that smoking is a cause of pancreatic cancer in women and that the risks for female smokers are comparable to male smokers. Nevertheless, the causes of most pancreatic cancers are unknown.
Tobacco-specific N-nitrosamines are a group of carcinogens derived from the tobacco alkaloids. They are likely causative factors for cancers of the lung, esophagus, pancreas, and oral cavity in people who use tobacco products. The most carcinogenic tobacco-specific nitrosamines in laboratory animals are 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and N'-nitrosonornicotine (NNN). DNA adduct formation from NNK and NNN has been studied extensively and is reviewed here. NNK is metabolically activated by cytochromes P450 to intermediates which methylate and pyridyloxobutylate DNA. The resulting adducts have been detected in cells and tissues susceptible to NNK carcinogenesis in rodents. The methylation and pyridyloxobutylation pathways are both important in carcinogenesis by NNK. NNK also induces single strand breaks and increases levels of 8-oxodeoxyguanosine in DNA of treated animals. NNAL, which like NNK is a potent pulmonary carcinogen, is also metabolically activated to methylating and pyridyloxobutylating intermediates. NNN pyridyloxobutylates DNA in its rat target tissues, esophagus and nasal mucosa. Methyl and pyridyloxobutyl DNA adducts are detected in human tissues. The methyl adducts most likely result in part from exposure of smokers to NNK, but these adducts are also detected in non-smokers. Some of the methyl adducts detected in non-smokers may be due to environmental tobacco smoke exposure. There are also potential dietary and endogenous sources of these adducts. Pyridyloxobutyl DNA adducts in human tissues result mainly from exposure to tobacco-specific N-nitrosamines. In laboratory animals, DNA adduct formation and carcinogenicity of tobacco-specific N-nitrosamines are closely correlated in many instances, and it is likely that similar relationships will hold in humans.
Previous studies reported an increased risk of pancreatic cancer among persons with diabetes. Few data exist, however, on the association of postload plasma glucose concentration with pancreatic cancer, which could provide insight into the role of abnormal glucose metabolism in the etiology of pancreatic cancer.
To determine the independent association between postload plasma glucose concentration and risk of pancreatic cancer mortality among persons without self-reported diabetes.
Prospective cohort study.
Employees of 84 Chicago-area organizations, with an average age of 40 years at baseline, were screened from 1963 to 1973 and followed up for an average of 25 years. A total of 96 men and 43 women died of pancreatic cancer among 20,475 men and 15,183 women, respectively.
Relationship of pancreatic cancer mortality with postload plasma glucose levels.
Compared with a postload plasma glucose level of 6.6 mmol/L (119 mg/dL) or less and after adjusting for age, race, cigarette smoking, and body mass index, the relative risks (95% confidence intervals) of pancreatic cancer mortality were 1.65 (1.05-2.60) for postload plasma glucose levels between 6.7 (120) and 8.8 (159) mmol/L (mg/dL); 1.60 (0.95-2.70) for levels between 8.9 (160) and 11.0 (199); and 2.15 (1.22-3.80) for levels of 11.1 (200) or more; P for trend=.01. An association appeared to be stronger for men than women. Estimates were only slightly lower after excluding 11 men and 2 women who died of pancreatic cancer during the first 5 years of follow-up. In men only, higher body mass index and serum uric acid concentration also were independently associated with an elevated risk of pancreatic cancer mortality.
These results suggest that factors associated with abnormal glucose metabolism may play an important role in the etiology of pancreatic cancer. JAMA. 2000;283:2552-2558
To investigate the association between cigarette smoking and use of oral moist snuff and impaired glucose tolerance and type 2 diabetes.
We performed a population-based cross-sectional study of glucose intolerance and tobacco use in Stockholm during 1992-94. The sample consisted of 3128 men, aged 35-56 years, of whom 52% had a family history of diabetes. In an oral glucose tolerance test, we detected 55 men with type 2 diabetes and 172 with impaired glucose tolerance. Information on cigarette smoking and oral moist snuff use was collected by a questionnaire.
The odds ratio of type 2 diabetes was increased for smokers of 25+ cigarettes day-1 (odds ratio = 2.6, 95% confidence interval = 1.1-5.9) as well as for moist snuff dippers of 3+ boxes week-1 (odds ratio = 2.7, 95% confidence interval = 1.3-5.5). The odds ratio of relatively high (highest tertile) fasting insulin levels in subjects with impaired glucose tolerance associated with cigarette smoking of 25+ cigarettes day-1 was 1.5 (95% confidence interval = 0.7-3.6). The corresponding estimate of a relatively low (lowest tertile) 2 h insulin response was 2.5 (95% confidence interval = 0.9-7.1).
These results indicate that heavy users of cigarettes or moist snuff have an increased risk of type 2 diabetes. The results could suggest that tobacco use is associated with a low insulin response.
Cancer of the pancreas is the fourth leading cause of cancer mortality in the USA with an estimated 28 900 deaths in 2001. Several factors have been implicated in the etiology of this disease. However, at present, only cigarette smoking has been positively associated with pancreatic cancer. It is our working hypothesis that tobacco-derived compounds can be delivered to the pancreas where, upon metabolic activation, they can initiate carcinogenesis. Our current investigation was conducted to determine whether cotinine and tobacco-specific nitrosamines (TSNA) are present in human pancreatic juice. Smoking status was assessed by the determination of levels of urinary cotinine and was further supported by quantifying nicotine in hair. The TSNA were extracted from the pancreatic juice of 18 smokers and 9 nonsmokers by supercritical carbon dioxide that contained 10% methanol. The extracts were analyzed for TSNA, namely, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN), by gas chromatography with mass spectrometric detection using a selected ion monitoring technique (GC-SIM-MS). Twenty-three extracts of human pancreatic juice were also analyzed for the presence of the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by GC-SIM-MS and by gas chromatography interfaced wit a thermal energy analyzer (GC-TEA; TEA, a nitrosamine-specific detector). Cotinine was detected in all analyzed samples of pancreatic juice from smokers (129 +/- 150 ng/mL juice; mean +/- standard deviation) and was present in only two of the nine samples of pancreatic juice from nonsmokers. Its levels in these two samples were 7 and 9 ng/mL juice. NNK was detected in 15 of 18 samples (83%) from smokers at levels from 1.37 to 604 ng/mL pancreatic juice. In nine samples of pancreatic juice from nonsmokers, NNK ranged from not detected (in three samples) to 96.8 ng/mL juice. In pancreatic juice from smokers the mean level of NNK (88.7 +/- 161 ng/mL juice) was significantly higher (p < 0.04) than in that from nonsmokers (12.4 +/- 31.7 ng/mL juice). In addition to NNK, NNN was found in two samples of pancreatic juice of smokers at levels of 68.1 and 242 ng/mL juice; NNN was not detected in any other sample. NNAL was present in 8 of 14 pancreatic juice samples (57%) from smokers and in three of nine samples (33%) from nonsmokers. This research presents preliminary data that supports the hypothesis that pancreatic tissue is exposed to TSNA and that they may be important contributors to pancreatic carcinogenesis in humans.
Adenocarcinoma of the lungs and pancreas are among the most common and most deadly smoking-associated cancers. Cigarette smoke contains various toxic chemicals, including a carcinogenic nitrosamine, nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). One of the most well-known features of NNK is the ability of its metabolites to bind to DNA and induce activating point mutations in the RAS gene. But NNK is also a β-adrenergic-receptor agonist that stimulates arachidonic acid release, leading to the formation of mitogenic metabolites that stimulate DNA synthesis and cell proliferation. NNK therefore contributes to tobacco-induced carcinogenesis by several mechanisms.
For many years Swedish men have had the world's lowest rates of smoking and smoking-related mortality. Despite these facts, a thorough analysis of tobacco use patterns in Sweden has not been performed. The purpose of this study was to examine the prevalence and interaction of cigarette smoking and use of Swedish moist snuff (snus) in the population of northern Sweden.
The study cohort of 2998 men and 3092 women aged 25-64 was derived from the northern Sweden MONICA study, consisting of population-based surveys in 1986, 1990, 1994 and 1999. Detailed information on tobacco use was used to develop prevalence data, and the prevalence ratio was used to compare rates amongst various subgroups.
Amongst men ever-tobacco use was stable in all survey years at about 65%, but the prevalence of smoking declined from 23% in 1986 to 14% in 1999, whilst snus use increased from 22% to 30%. In women the prevalence of smoking was more stable in the first three surveys (approximately 27%) but was 22% in 1999, when snus use was 6%. In all years men showed higher prevalence of ex-smoking than women. A dominant factor was a history of snus (PR = 6.18, CI = 4.96-7.70), which was more prevalent at younger ages.
The recent transition from smoking to snus use amongst men, and incipiently amongst women, in northern Sweden is remarkable and relevant to the global discussion on strategies to reduce smoking.
To assess to what extent snus has been used as an aid to stop smoking among Swedish smokers.
A random telephone retrospective survey of Swedish smokers and ex-smokers.
Survey conducted in November-December 2000.
A national sample of 1000 former and 985 current daily smokers aged 25-55 years.
Smoking status, date and method of quitting by self-report.
Thirty-three per cent of former smokers and 27% of current smokers had ever used snus. The difference was larger among men (55% versus 45%, P = 0.003). Current smokers who made use of snus smoked on average fewer cigarettes per day than non-users of snus. The mean duration of abstinence among former smokers was not influenced by snus use. Conditionally on age, education and use of nicotine replacement therapy there was an increased probability of being a former rather than a current smoker with ever use (OR 1.72, 95% CI = 1.30-2.28) or current use (OR 1.81, 95% CI = 1.31-2.53) of snus. Having used snus at the latest quit attempt increased the probability of being abstinent by about 50% (OR 1.54, 95% CI = 1.09-2.20).
Our study suggests that by using snus, Swedish male smokers may increase their overall chances of abstinence. However, 71% of the men in this sample who quit smoking did so without using snus and the duration of abstinence was not affected by snus use. This suggests that snus is not a necessary component of smoking cessation at the population level. Snus use was very rare among women.
Cigarette smoking is an important and well-established cause of pancreatic cancer. In contrast, little is known about the effects of smoking cigars, pipes, and use of smokeless tobacco on pancreatic cancer risk. The objective of the present study was to examine the association between noncigarette tobacco use (i.e., cigars, pipes, smokeless tobacco) and pancreatic cancer risk among nonsmokers of cigarettes. A population-based case-control study of pancreatic cancer was conducted during 1986-1989 among residents of Atlanta, Georgia, Detroit, Michigan, and 10 counties in New Jersey. Direct interviews were successfully completed with 526 newly diagnosed pancreatic cancer patients and 2153 controls ages 30-79 years. This analysis was restricted to lifelong nonsmokers of cigarettes and based on interviews with 154 cases newly diagnosed with carcinoma of the exocrine pancreas and 844 population controls who reported no history of cigarette smoking. We observed a consistent pattern of increased risk associated with cigar smoking, although these elevations were not statistically significant. Participants who smoked cigars regularly (i.e., at least one cigar/week for >/=6 months) experienced a 70% increased risk [95% confidence interval (CI): 0.9-3.3], and those who never used other form of tobacco had a 90% increased risk (95% CI: 0.8-4.3). Risk was elevated among those who smoked more than one cigar/day [odds ratio (OR) = 1.8; 95% CI: 0.8-4.2) and among those who smoked cigars > 20 years (OR = 1.9; 95% CI: 0.9-3.9). Trends in risk with increasing amount and duration smoked were consistent but not statistically significant (P = 0.17 and P = 0.16, respectively). Subjects who used smokeless tobacco regularly had a 40% increased risk of pancreatic cancer (95% CI: 0.5-3.6) compared with nonusers of tobacco. We observed a marginally significant increasing risk with increased use of smokeless tobacco (P = 0.04); participants who used >2.5 oz of smokeless tobacco a week had an OR of 3.5 (95% CI: 1.1-11). Long-term use of smokeless tobacco (i.e., >20 years) was also associated with a nonsignificant increased risk (OR = 1.5; 95% CI: 0.6-4.0). In contrast, pipe smokers experienced no increased risk (OR = 0.6; 95% CI: 0.1-2.8). Our results suggest that heavy use of smokeless tobacco, and to a lesser extent, cigar smoking may increase the risk of pancreatic cancer among nonsmokers of cigarettes.
Limited data are available on the carcinogenicity of smokeless tobacco products in organs other than the mouth. Snus is a smokeless tobacco product widely used in Norway. We studied 10,136 Norwegian men enrolled since 1966 in a prospective cohort study, 31.7% of whom were exposed to snus. The relative risk of pancreatic cancer for snus use was 1.67 (95% confidence interval [CI] = 1.12, 2.50); that of oral and pharyngeal cancer was 1.10 (95% CI = 0.50, 2.41), that of esophageal cancer was 1.40 (95% CI = 0.61, 3.24), and that of stomach cancer was 1.11 (95% CI = 0.83, 1.48). The relative risks of cancers of the lung (either all histological types or adenocarcinoma), urinary bladder and kidney were not increased among snus users. The increase in the relative risk of pancreatic cancer was similar in former and current snus users and was restricted to current tobacco smokers. Our study suggests that smokeless tobacco products may be carcinogenic on the pancreas. Tobacco-specific N-nitrosamines are plausible candidates for the carcinogenicity of smokeless tobacco products in the pancreas.
Few prospective studies have examined the health risks associated with use of snuff and chewing tobacco.
We studied the association between the use of spit tobacco (snuff or chewing tobacco) and mortality among men enrolled in Cancer Prevention Study I (CPS-I) in 1959 or Cancer Prevention Study II (CPS-II) in 1982. Analyses were based on men who reported exclusive use of snuff or chewing tobacco (7745 in CPS-I, 3327 in CPS-II) or no previous use of any tobacco product (69,662 in CPS-I, 111,482 in CPS-II) at baseline. Twelve-year follow-up of CPS-I, and 18-year follow-up of CPS-II identified 11,871 and 19,588 deaths, respectively. Cox proportional hazards models were used to control for age and other covariates.
Men who currently used snuff or chewing tobacco at baseline had higher death rates from all causes than men who did not in both CPS-I (hazard ratio [HR]=1.17, 95% CI=1.11-1.23) and CPS-II (HR=1.18, 95% CI=1.08-1.29). In CPS-I, current use of spit tobacco was statistically significantly associated with death from coronary heart disease (CHD), stroke, and diseases of the respiratory, digestive, and genitourinary systems, but not with death from cancer. In CPS-II, use of these products was significantly associated with death from CHD, stroke, all cancers combined, lung cancer, and cirrhosis. The associations with cardiovascular and other non-malignant endpoints were attenuated, but not eliminated, by controlling for measured covariates. Former use of spit tobacco was not associated with any endpoint in CPS-II. No clear dose response was observed with either the frequency or duration of usage for any endpoint.
These two prospective studies provide limited evidence that current use of chewing tobacco or snuff may increase mortality from heart disease and stroke.
Smokeless tobacco (ST) use remains a prevalent form of tobacco use among certain US populations. The purpose of this paper is to clarify its role in cancer development.
Using data from a prospective cohort of the US population, we categorized 6,779 subjects 45-75 years of age as ST users or non-ST users. Subjects were further stratified by cigarette smoking status in order to differentiate 'exclusive' ST users (n=414) from never tobacco users (n=2,979).
In this cohort, exclusive ST use was not associated with increased incidence of all cancer in males (hazard ratio=0.8, 95% CI: 0.4, 1.6) or females (HR=1.2, 95% CI: 0.7-2.1) or oral cancer (standardized incidence ratio=30, 95% CI: 3, 95). No synergistic effect was observed between ST and cigarette smoking among male combined users (females were not analyzed for combined use) for the major cancers.
In contrast to the well-known deleterious effects of cigarette smoking, ST use did not substantially increase the risk for cancer incidence above that of non-tobacco users, particularly among males. Although the use of tobacco in any form is to be discouraged, our data suggests that cancer risks are much lower from ST use than from cigarette smoking.
To investigate the prevalence and patterns of transitions between cigarette and snus use.
Cross-sectional study within the population-based Swedish Twin Registry.
A total of 31 213 male and female twins 42-64 years old.
Age-adjusted prevalence odds ratios (POR) and 95% confidence intervals (CIs) described the association between gender and tobacco use, while Kaplan-Meier survival methods produced cumulative incidence curves of age at onset of tobacco use. Life-time tobacco use histories were constructed using ages at onset of tobacco use and current tobacco use status.
Although more males reported ever smoking (64.4%) than females (61.7%), more males were former smokers (POR: 1.33, 95% CI: 1.27-1.39). Males were far more likely to use snus than females (POR: 18.0, 95% CI: 16.17-20.04). Age at onset of cigarette smoking occurred almost entirely before age 25, while the age at onset of snus use among males occurred over a longer time period. Most men began using cigarettes first, nearly one-third of whom switched to using cigarettes and snus in combination. While 30.6% of these combined users quit tobacco completely, only 7.4% quit snus and currently use cigarettes, while 47.7% quit cigarettes and currently use snus.
Current cigarette smoking is more prevalent among Swedish women than men, while snus use is more prevalent among men. Among men who reported using both cigarettes and snus during their life-time, it was more common to quit cigarettes and currently use snus than to quit snus and currently use cigarettes. Once snus use was initiated, more men continued using snus rather than quit tobacco completely.
Pancreatic cancer Textbook of cancer epidemiology
- A Ekbom
- Hunter
39 Ekbom A, Hunter D. Pancreatic cancer. In: Adami HO, Hunter D, Trichopoulos D, eds. Textbook of cancer epidemiology. New York: Oxford University Press, 2002: 233–47.