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ABSTRACT: BACKGROUND: National smoking-specific lung cancer mortality rates are unavailable, and studies presenting estimates are limited, particularly by histology. This hinders interpretation. We attempted to rectify this by deriving estimates indirectly, combining data from national rates and epidemiological studies. METHODS: We estimated study-specific absolute mortality rates and variances by histology and smoking habit (never/ever/current/former) based on relative risk estimates derived from studies published in the 20th century, coupled with WHO mortality data for age 70--74 for the relevant country and period. Studies with populations grossly unrepresentative nationally were excluded. 70--74 was chosen based on analyses of large cohort studies presenting rates by smoking and age. Variations by sex, period and region were assessed by meta-analysis and meta-regression. RESULTS: 148 studies provided estimates (Europe 59, America 54, China 22, other Asia 13), 54 providing estimates by histology (squamous cell carcinoma, adenocarcinoma). For all smoking habits and lung cancer types, mortality rates were higher in males, the excess less evident for never smokers. Never smoker rates were clearly highest in China, and showed some increasing time trend, particularly for adenocarcinoma. Ever smoker rates were higher in parts of Europe and America than in China, with the time trend very clear, especially for adenocarcinoma. Variations by time trend and continent were clear for current smokers (rates being higher in Europe and America than Asia), but less clear for former smokers. Models involving continent and trend explained much variability, but non-linearity was sometimes seen (with rates lower in 1991--99 than 1981--90), and there was regional variation within continent (with rates in Europe often high in UK and low in Scandinavia, and higher in North than South America). CONCLUSIONS: The indirect method may be questioned, because of variations in definition of smoking and lung cancer type in the epidemiological database, changes over time in diagnosis of lung cancer types, lack of national representativeness of some studies, and regional variation in smoking misclassification. However, the results seem consistent with the literature, and provide additional information on variability by time and region, including evidence of a rise in never smoker adenocarcinoma rates relative to squamous cell carcinoma rates.
BMC Cancer 04/2013; 13(1):189. · 3.01 Impact Factor
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ABSTRACT: BACKGROUND: Reduced FEV1 is known to predict increased lung cancer risk, but previous reviews are limited. To quantify this relationship more precisely, and study heterogeneity, we derived estimates of beta for the relationship RR(diff) = exp(betadiff), where diff is the reduction in FEV1 expressed as a percentage of predicted (FEV1%P) and RR(diff) the associated relative risk. We used results reported directly as beta, and as grouped levels of RR in terms of FEV1%P and of associated measures (e.g. FEV1/FVC). METHODS: Papers describing cohort studies involving at least three years follow-up which recorded FEV1 at baseline and presented results relating lung cancer to FEV1 or associated measures were sought from Medline and other sources. Data were recorded on study design and quality and, for each data block identified, on details of the results, including population characteristics, adjustment factors, lung function measure, and analysis type. Regression estimates were converted to beta estimates where appropriate. For results reported by grouped levels, we used the NHANES III dataset to estimate mean FEV1%P values for each level, regardless of the measure used, then derived beta using regression analysis which accounted for non-independence of the RR estimates. Goodness-of-fit was tested by comparing observed and predicted lung cancer cases for each level. Inverse-variance weighted meta-analysis allowed derivation of overall beta estimates and testing for heterogeneity by factors including sex, age, location, timing, duration, study quality, smoking adjustment, measure of FEV1 reported, and inverse-variance weight of beta. RESULTS: Thirty-three publications satisfying the inclusion/exclusion criteria were identified, seven being rejected as not allowing estimation of beta. The remaining 26 described 22 distinct studies, from which 32 independent beta estimates were derived. Goodness-of-fit was satisfactory, and exp(beta), the RR increase per one unit FEV1%P decrease, was estimated as 1.019 (95%CI 1.016-1.021). The estimates were quite consistent (I2 =29.6%). Mean age was the only independent source of heterogeneity, exp(beta) being higher for age <50 years (1.024, 1.020-1.028). CONCLUSIONS: Although the source papers present results in various ways, complicating meta-analysis, they are very consistent. A decrease in FEV1%P of 10% is associated with a 20% (95%CI 17%-23%) increase in lung cancer risk.
BMC Cancer 10/2012; 12(1):498. · 3.01 Impact Factor
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ABSTRACT: BACKGROUND: Smoking is a known lung cancer cause, but no detailed quantitative systematic review exists. We summarize evidence for various indices. METHODS: Papers published before 2000 describing epidemiological studies involving 100+ lung cancer cases were obtained from Medline and other sources. Studies were classified as principal, or subsidiary where cases overlapped with principal studies. Data were extracted on design, exposures, histological types and confounder adjustment. RRs/ORs and 95% CIs were extracted for ever, current and ex smoking of cigarettes, pipes and cigars and indices of cigarette type and dose--response. Meta-analyses and meta-regressions investigated how relationships varied by study and RR characteristics, mainly for outcomes exactly or closely equivalent to all lung cancer, squamous cell carcinoma ("squamous") and adenocarcinoma ("adeno"). RESULTS: 287 studies (20 subsidiary) were identified. Although RR estimates were markedly heterogeneous, the meta-analyses demonstrated a relationship of smoking with lung cancer risk, clearly seen for ever smoking (random-effects RR 5.50, CI 5.07-5.96) current smoking (8.43, 7.63-9.31), ex smoking (4.30, 3.93-4.71) and pipe/cigar only smoking (2.92, 2.38-3.57). It was stronger for squamous (current smoking RR 16.91, 13.14-21.76) than adeno (4.21, 3.32-5.34), and evident in both sexes (RRs somewhat higher in males), all continents (RRs highest for North America and lowest for Asia, particularly China), and both study types (RRs higher for prospective studies). Relationships were somewhat stronger in later starting and larger studies. RR estimates were similar in cigarette only and mixed smokers, and similar in smokers of pipes/cigars only, pipes only and cigars only. Exceptionally no increase in adeno risk was seen for pipe/cigar only smokers (0.93, 0.62-1.40). RRs were unrelated to mentholation, and higher for non-filter and handrolled cigarettes. RRs increased with amount smoked, duration, earlier starting age, tar level and fraction smoked and decreased with time quit. Relationships were strongest for small and squamous cell, intermediate for large cell and weakest for adenocarcinoma. Covariate-adjustment little affected RR estimates. CONCLUSIONS: The association of lung cancer with smoking is strong, evident for all lung cancer types, dose-related and insensitive to covariate-adjustment. This emphasises the causal nature of the relationship. Our results quantify the relationships more precisely than previously.
BMC Cancer 09/2012; 12(1):385. · 3.01 Impact Factor
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ABSTRACT: No previous review has formally modelled the decline in IHD risk following quitting smoking. From PubMed searches and other sources we identified 15 prospective and eight case-control studies that compared IHD risk in current smokers, never smokers, and quitters by time period of quit, some studies providing separate blocks of results by sex, age or amount smoked. For each of 41 independent blocks, we estimated, using the negative exponential model, the time, H, when the excess risk reduced to half that caused by smoking. Goodness-of-fit to the model was adequate for 35 blocks, others showing a non-monotonic pattern of decline following quitting, with a variable pattern of misfit. After omitting one block with a current smoker RR 1.0, the combined H estimate was 4.40 (95% CI 3.26-5.95) years. There was considerable heterogeneity, H being <2years for 10 blocks and >10years for 12. H increased (p<0.001) with mean age at study start, but not clearly with other factors. Sensitivity analyses allowing for reverse causation, or varying assumed midpoint times for the final open-ended quitting period little affected goodness-of-fit of the combined estimate. The US Surgeon-General's view that excess risk approximately halves after a year's abstinence seems over-optimistic.
Regulatory Toxicology and Pharmacology 06/2012; 64(1):51-67. · 2.43 Impact Factor
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ABSTRACT: Recent studies have compared rates of acute myocardial infarction before and after introducing smoking bans. Some meta-analyses report post-ban reductions up to 19%, implausibly large considering likely changes in smoking habits and passive smoke exposure. Our literature reassessment demonstrates major weaknesses in many studies and meta-analyses, including failure to consider data from control areas or existing trends in acute myocardial infarction rates, incorrect estimation of variability, and use in some meta-analyses of results for population subsets or estimates apparently unrelated to the data reported. We report meta-analyses using a consistent approach to derive estimates of the ban effect, taking account of time trends and control data, which indicate a much smaller reduction. Preferring national to regional estimates where available, we estimate a 5% reduction (95% CI 3-8%). Omitting estimates where trend adjustment was impossible, this becomes 2.7% (2.1-3.4%), consistent with reported declines of 2-3% in large national populations (England, France, Italy, USA). We discuss some limitations of these estimates. Further evidence is needed, possibly by analyzing national mortality data. Our findings highlight the need for a valid approach when estimating the effect of bans, and demonstrate major weaknesses in many previous publications.
Regulatory Toxicology and Pharmacology 09/2011; 61(3):318-31. · 2.43 Impact Factor
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ABSTRACT: Smoking is a known cause of the outcomes COPD, chronic bronchitis (CB) and emphysema, but no previous systematic review exists. We summarize evidence for various smoking indices.
Based on MEDLINE searches and other sources we obtained papers published to 2006 describing epidemiological studies relating incidence or prevalence of these outcomes to smoking. Studies in children or adolescents, or in populations at high respiratory disease risk or with co-existing diseases were excluded. Study-specific data were extracted on design, exposures and outcomes considered, and confounder adjustment. For each outcome RRs/ORs and 95% CIs were extracted for ever, current and ex smoking and various dose response indices, and meta-analyses and meta-regressions conducted to determine how relationships were modified by various study and RR characteristics.
Of 218 studies identified, 133 provide data for COPD, 101 for CB and 28 for emphysema. RR estimates are markedly heterogeneous. Based on random-effects meta-analyses of most-adjusted RR/ORs, estimates are elevated for ever smoking (COPD 2.89, CI 2.63-3.17, n = 129 RRs; CB 2.69, 2.50-2.90, n = 114; emphysema 4.51, 3.38-6.02, n = 28), current smoking (COPD 3.51, 3.08-3.99; CB 3.41, 3.13-3.72; emphysema 4.87, 2.83-8.41) and ex smoking (COPD 2.35, 2.11-2.63; CB 1.63, 1.50-1.78; emphysema 3.52, 2.51-4.94). For COPD, RRs are higher for males, for studies conducted in North America, for cigarette smoking rather than any product smoking, and where the unexposed base is never smoking any product, and are markedly lower when asthma is included in the COPD definition. Variations by sex, continent, smoking product and unexposed group are in the same direction for CB, but less clearly demonstrated. For all outcomes RRs are higher when based on mortality, and for COPD are markedly lower when based on lung function. For all outcomes, risk increases with amount smoked and pack-years. Limited data show risk decreases with increasing starting age for COPD and CB and with increasing quitting duration for COPD. No clear relationship is seen with duration of smoking.
The results confirm and quantify the causal relationships with smoking.
BMC Pulmonary Medicine 06/2011; 11:36. · 1.33 Impact Factor
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Peter N Lee
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ABSTRACT: US mentholated cigarette sales have increased considerably over 50 years. Preference for mentholated cigarettes is markedly higher in Black people. While menthol itself is not genotoxic or carcinogenic, its acute respiratory effects might affect inhalation of cigarette smoke. This possibility seems consistent with the higher lung cancer risk in Black men, despite Black people smoking less and starting smoking later than White people. Despite experimental data suggesting similar carcinogenicity of mentholated and non-mentholated cigarettes, the lack of convincing evidence that mentholation increases puffing, inhalation or smoke uptake, and the similarity of lung cancer rates in Black and White females, a review of cigarette mentholation and lung cancer is timely given current regulatory interest in the topic.
Epidemiological studies comparing lung cancer risk in mentholated and non-mentholated cigarette smokers were identified from MedLine and other sources. Study details were extracted and strengths and weaknesses assessed. Relative risk estimates were extracted, or derived, for ever mentholated use and for long-term use, overall and by gender, race, and current/ever smoking, and meta-analyses conducted.
Eight generally good quality studies were identified, with valid cases and controls, and appropriate adjustment for age, gender, race and smoking. The studies afforded good power to detect possible effects. However, only one study presented results by histological type, none adjusted for occupation or diet, and some provided no results by length of mentholated cigarette use.The data do not suggest any effect of mentholation on lung cancer risk. Adjusted relative risk estimates for ever use vary from 0.81 to 1.12, giving a combined estimate of 0.93 (95% confidence interval 0.84-1.02, n = 8), with no increase in males (1.01, 0.84-1.22, n = 5), females (0.80, 0.67-0.95, n = 5), White people (0.87, 0.75-1.03, n = 4) or Black people (0.90, 0.73-1.10, n = 4). Estimates for current and ever smokers are similar. The combined estimate for long-term use (0.95, 0.80-1.13, n = 4) again suggests no effect of mentholation.
Higher lung cancer rates in Black males cannot be due to their greater preference for mentholated cigarettes. While some study weaknesses exist, the epidemiological evidence is consistent with mentholation having no effect on the lung carcinogenicity of cigarettes.
BMC Pulmonary Medicine 01/2011; 11:18. · 1.33 Impact Factor
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Peter N Lee
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ABSTRACT: Interest in snus (Swedish-type moist snuff) as a smoking alternative has increased. This wide-ranging review summarizes evidence relating snus to health and to initiation and cessation of smoking. Meta-analyses are included. After smoking adjustment, snus is unassociated with cancer of the oropharynx (meta-analysis RR 0.97, 95% CI 0.68-1.37), oesophagus (1.10, 0.92-1.33), stomach (0.98, 0.82-1.17), pancreas (1.20, 0.66-2.20), lung (0.71, 0.66-0.76) or other sites, or with heart disease (1.01, 0.91-1.12) or stroke (1.05, 0.95-1.15). No clear associations are evident in never smokers, any possible risk from snus being much less than from smoking. "Snuff-dipper's lesion" does not predict oral cancer. Snus users have increased weight, but diabetes and chronic hypertension seem unaffected. Notwithstanding unconfirmed reports of associations with reduced birthweight, and some other conditions, the evidence provides scant support for any major adverse health effect of snus. Although some claims that snus reduces initiation or encourages quitting are unsoundly based, snus seems not to increase initiation, as indicated by few smokers using snus before starting and current snus use being unassociated with smoking in adults (the association in children probably being due to uncontrolled confounding), and there are no reports that snus discourages quitting.
Regulatory Toxicology and Pharmacology 12/2010; 59(2):197-214. · 2.43 Impact Factor
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ABSTRACT: The rate of forced expiratory volume in 1 second (FEV1) decline ("beta") is a marker of chronic obstructive pulmonary disease risk. The reduction in beta after quitting smoking is an upper limit for the reduction achievable from switching to novel nicotine delivery products. We review available evidence to estimate this reduction and quantify the relationship of smoking to beta.
Studies were identified, in healthy individuals or patients with respiratory disease, that provided data on beta over at least 2 years of follow-up, separately for those who gave up smoking and other smoking groups. Publications to June 2010 were considered. Independent beta estimates were derived for four main smoking groups: never smokers, ex-smokers (before baseline), quitters (during follow-up) and continuing smokers. Unweighted and inverse variance-weighted regression analyses compared betas in the smoking groups, and in continuing smokers by amount smoked, and estimated whether beta or beta differences between smoking groups varied by age, sex and other factors.
Forty-seven studies had relevant data, 28 for both sexes and 19 for males. Sixteen studies started before 1970. Mean follow-up was 11 years. On the basis of weighted analysis of 303 betas for the four smoking groups, never smokers had a beta 10.8 mL/yr (95% confidence interval (CI), 8.9 to 12.8) less than continuing smokers. Betas for ex-smokers were 12.4 mL/yr (95% CI, 10.1 to 14.7) less than for continuing smokers, and for quitters, 8.5 mL/yr (95% CI, 5.6 to 11.4) less. These betas were similar to that for never smokers. In continuing smokers, beta increased 0.33 mL/yr per cigarette/day. Beta differences between continuing smokers and those who gave up were greater in patients with respiratory disease or with reduced baseline lung function, but were not clearly related to age or sex.
The available data have numerous limitations, but clearly show that continuing smokers have a beta that is dose-related and over 10 mL/yr greater than in never smokers, ex-smokers or quitters. The greater decline in those with respiratory disease or reduced lung function is consistent with some smokers having a more rapid rate of FEV1 decline. These results help in designing studies comparing continuing smokers of conventional cigarettes and switchers to novel products.
BMC Medicine 01/2010; 8:84. · 6.03 Impact Factor
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ABSTRACT: In a previous analysis (see Part I) we proposed a heuristic for assessing the efficacy of potential reduced-risk tobacco products (PRRPs) on lung cancer (LC) rates, using smoking cessation data published in a report from the Iowa Women's Health Study (IWHS) as a basis for sample size estimates. In this study, an additional analysis was performed using cessation data from the much larger Cancer Prevention Study II (CPS-II), which also provides data on different durations of cessation. Statistical methods were used to assess whether smokers switching to a PRRP would reduce their risk of LC. Furthermore, non-inferiority tests compared the LC risk in switchers to that in smokers who had quit smoking. The present work shows that similar sample size estimates were obtained whether the analysis was based on the IWHS or the CPS-II data sets, suggesting that the heuristic may be generally applicable to prospective real-life studies to evaluate PRRPs. Non-inferiority testing of switchers compared with quitters required approximately 10-fold more subjects than did superiority testing of switchers compared with smokers. Altogether, these estimates indicate that it is feasible, in terms of study duration and sample size, to clinically assess the LC risk-reducing potential of a PRRP.
Regulatory Toxicology and Pharmacology 12/2009; 57(1):11-7. · 2.43 Impact Factor
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Lenn Murrelle,
Christopher R E Coggins,
Chris Gennings,
Richard A Carchman,
Walter H Carter,
Bruce D Davies,
Marc R Krauss, Peter N Lee,
Raymond R Schleef,
Barbara K Zedler,
Christian Heidbreder
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ABSTRACT: The risk-reducing effect of a potential reduced-risk tobacco product (PRRP) can be investigated conceptually in a long-term, prospective study of disease risks among cigarette smokers who switch to a PRRP and in appropriate comparison groups. Our objective was to provide guidance for establishing the fundamental design characteristics of a study intended to (1) determine if switching to a PRRP reduces the risk of lung cancer (LC) compared with continued cigarette smoking, and (2) compare, using a non-inferiority approach, the reduction in LC risk among smokers who switched to a PRRP to the reduction in risk among smokers who quit smoking entirely. Using standard statistical methods applied to published data on LC incidence after smoking cessation, we show that the sample size and duration required for a study designed to evaluate the potential for LC risk reduction for an already marketed PRRP, compared with continued smoking, varies depending on the LC risk-reducing effectiveness of the PRRP, from a 5-year study with 8000-30,000 subjects to a 15-year study with <5000 to 10,000 subjects. To assess non-inferiority to quitting, the required sample size tends to be about 10 times greater, again depending on the effectiveness of the PRRP.
Regulatory Toxicology and Pharmacology 12/2009; 57(1):1-10. · 2.43 Impact Factor
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ABSTRACT: We compared risk of lung cancer and chronic obstructive pulmonary disease (COPD) associated with flue-cured and blended cigarettes. Mortality and smoking data were collected for 1971-2000 by sex, age, and period for three countries with a mainly flue-cured market and four with a blended market. Epidemiological relative risk estimates for current and ex smoking were summarized. Smoking statistics and mortality were compared between flue-cured cigarette and blended cigarette countries. Unadjusted mortality rates were generally lower in blended cigarette countries early on, with the difference diminishing or reversing by the 1990s. Differences by cigarette type were rarely significant, due to variations, particularly for COPD, between countries within cigarette type. Current smoking prevalence was generally lower in blended cigarette countries in 1971-1975, with the difference reducing over time. Differences by type were never significant, with blended cigarette countries varying markedly. Ex-smoking increased over time and was lower for blended cigarette countries, generally not significantly. Consumption per smoker was somewhat lower for blended cigarette countries. Relative risk estimates for smoking, derived mainly from U.S. and UK studies, varied little by cigarette type. Conclusions based on estimated smoking-related excess mortality were similar to those based on unadjusted mortality rates. There was little indication of any difference between flue-cured and blended cigarettes on risk of lung cancer or COPD. Our approach could have detected differences of about 40% for male lung cancer, or twofold differences for females or for COPD, had they existed. Between-country differences in rates of two major diseases predominantly caused by smoking cannot materially be explained by whether the countries use flue-cured or blended cigarettes.
Inhalation Toxicology 05/2009; 21(5):404-30. · 1.92 Impact Factor
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ABSTRACT: How smokeless tobacco contributes to non-neoplastic oral diseases is unclear. It certainly increases risk of oral mucosal lesions, but reviewers disagree as to other conditions. In some areas, especially South-East Asia, risk is difficult to quantify due to the many products, compositions (including non-tobacco ingredients), and usage practices involved. This review considers studies from Europe (in practice mainly Scandinavia) and from the USA.
Experimental and epidemiological studies published in 1963-2007 were identified that related risk of oral lesions to smokeless tobacco use. Data were assessed separately for oral mucosal lesions, periodontal and gingival diseases, dental caries and tooth loss, and oral pain.
Oral mucosal lesions: Thirty-three epidemiological studies consistently show a strong dose-related effect of current snuff on oral mucosal lesion prevalence. In Scandinavia, users have a near 100% prevalence of a characteristic "snuff-induced lesion", but prevalence of the varied lesions reported in the USA is lower. Associations with chewing tobacco are weaker. The lack of clear association with former use suggests reversibility following cessation, consistent with experimental studies showing rapid lesion regression on quitting.Periodontal and gingival diseases: Two of four studies report a significant association of snuff with attachment loss and four out of eight with gingival recession. Snuff is not clearly related to gingivitis or periodontal diseases. Limited evidence suggests chewing tobacco is unrelated to periodontal or gingival diseases.Tooth loss: Swedish studies show no association with snuff, but one US study reported an association with snuff, and another with chewing tobacco.Dental caries: Evidence from nine studies suggests a possible relationship with use of smokeless tobacco, particularly chewing tobacco, and the risk of dental caries.Oral pain: Limited evidence precludes any clear conclusion.
This review confirms the strong association of current use of smokeless tobacco, particularly snuff, with prevalence of oral mucosal lesions. It provides suggestive evidence of an association of snuff use with gingival recession and attachment loss, and of chewing tobacco with dental caries. While smokeless tobacco clearly increases risk of oral mucosal lesions, interpretation for other endpoints is limited by study weaknesses, including poor confounding control.
BMC Oral Health 02/2008; 8:13.
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ABSTRACT: Menthol (2-isopropyl-5-methyl-cyclohexan-1-ol) is used in food, pharmaceutical, and tobacco products. Despite its long usage history and GRAS status, scientific literature on effects of cigarette mentholation is limited. Because African-American men have high lung cancer rates and predominantly smoke mentholated cigarettes, and because menthol's cooling effect might affect puffing and smoke inhalation, possible adverse effects of cigarette mentholation have been suggested. We review the evidence on the effects of mentholation on smokers, and we also identify areas for further study. Five large epidemiological studies provide no evidence that cigarette mentholation increases lung cancer risk. Mentholation cannot explain the higher risk for lung cancer in African-American male smokers, who also predominantly smoke mentholated cigarettes. Limited data on other cancers also suggest no risk from mentholation. The scientific literature suggests that cigarette mentholation does not increase puff number or puff volume of smoked cigarettes, and has little or no effect on heart rate, blood pressure, uptake of carbon monoxide, tar intake or retention, or blood cotinine concentration. Mentholation has little effect on other smoke constituents, and no apparent effect on nicotine absorption, airway patency and smoking initiation, dependency or cessation. Any toxicological effects of cigarette mentholation on adult smokers are probably quite limited.
Regulatory Toxicology and Pharmacology 04/2007; 47(2):189-203. · 2.43 Impact Factor
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ABSTRACT: Smokeless tobacco is often referred to as a major contributor to oral cancer. In some regions, especially Southeast Asia, the risk is difficult to quantify due to the variety of products, compositions (including non-tobacco ingredients) and usage practices involved. In Western populations, the evidence of an increased risk in smokeless tobacco users seems unclear, previous reviews having reached somewhat differing conclusions. We report a detailed quantitative review of the evidence in American and European smokeless tobacco users, and compare our findings with previous reviews and meta-analyses.
Following literature review a meta-analysis was conducted of 32 epidemiological studies published between 1920 and 2005 including tests for homogeneity and publication bias.
Based on 38 heterogeneous study-specific estimates of the odds ratio or relative risk for smokeless tobacco use, the random-effects estimate was 1.87 (95% confidence interval 1.40-2.48). The increase was mainly evident in studies conducted before 1980. No increase was seen in studies in Scandinavia. Restricting attention to the seven estimates adjusted for smoking and alcohol eliminated both heterogeneity and excess risk (1.02; 0.82-1.28). Estimates also varied by sex (higher in females) and by study design (higher in case-control studies with hospital controls) but more clearly in studies where estimates were unadjusted, even for age. The pattern of estimates suggests some publication bias. Based on limited data specific to never smokers, the random-effects estimate was 1.94 (0.88-4.28), the eight individual estimates being heterogeneous and based on few exposed cases.
Smokeless tobacco, as used in America or Europe, carries at most a minor increased risk of oral cancer. However, elevated risks in specific populations or from specific products cannot definitely be excluded.
BMC Public Health 02/2007; 7:334. · 2.00 Impact Factor
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ABSTRACT: Recent authoritative reviews consider smoking has no effect on breast cancer risk, but some studies report an increase from environmental tobacco smoke (ETS). We reviewed the overall evidence on ETS and breast cancer in nonsmoking women. We extracted details of available studies, derived relative risk (RR) estimates with confidence intervals (CIs) for various ETS exposure indices and conducted meta-analyses. Using an index for each study most closely equivalent to "spouse ever smoked," a weak, but significant, association was seen (random-effects RR = 1.12, 95% CI = 1.02-1.24, n = 22). However, the estimates were heterogeneous: close to 1.0 for prospective, North American and larger studies, and those adjusting for many potential confounders, but significantly (p < .05) elevated in case-control, European, and smaller studies, and those accounting for fewer potential confounders. Risk was increased in premenopausal women (RR = 1.54, 95% CI = 1.16-2.05, n = 10), but not postmenopausal women. Dose-response findings were similarly heterogeneous. No significant increase was seen for ETS in childhood or the workplace or from the spouse specifically, but an increase was seen for total exposure (RR = 1.54, 95% CI = 1.17-2.04, n = 6). Increases mainly derive from case-control studies asking detailed ETS histories, where RRs depend heavily on who is classified in the totally unexposed reference group, and may be prone to recall bias. Results from prospective studies using similar histories are needed. Study weaknesses and possible publication bias also limit interpretation. Because of the inherent implausibility that ETS exposure might cause breast cancer, given the similar risks of smokers and nonsmokers, one cannot confidently conclude ETS exposure increases risk in nonsmokers.
Inhalation Toxicology 01/2007; 18(14):1053-70. · 1.92 Impact Factor
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ABSTRACT: This study has examined the possible effects of ammonia-forming ingredients added to tobacco and of ammonia in mainstream (MS) smoke on the nicotine transfer from tobacco to smoke. The U.S. 1998 Marlboro Lights King Size cigarette was used as a control for four test variants that differed from the control as follows: first, a reduction in ammonia-forming ingredients added to the reconstituted tobaccos; second, no ammonia-forming ingredients added to the reconstituted tobaccos; third, no ingredients at all added to the reconstituted tobaccos; and fourth, no ingredients at all added to the entire tobacco blend. Data were obtained on nicotine in tobacco, tar and nicotine and ammonia in MS smoke, soluble ammonia in the cigarette tobacco, "tobacco pH," and "smoke pH" using the FTC machine-smoking paradigm. Previous research on these cigarettes demonstrated that >99% of the MS smoke nicotine was captured and quantified by the FTC method. Statistically significant increases in soluble ammonia and MS smoke ammonia were observed for those cigarettes with ammonia-forming ingredients added to the reconstituted tobacco. However, ingredients, including ammonia and ammonia-forming compounds added to the tobacco or ammonia in the mainstream smoke in the Marlboro Lights King Size cigarette, did not increase the relative nicotine transfer or the "pH of aqueous extracts of MS smoke." "Tobacco pH" and "smoke pH" had no scientific or practical value for the cigarettes in this study.
Regulatory Toxicology and Pharmacology 10/2006; 46(1):1-17. · 2.43 Impact Factor
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ABSTRACT: Between 1985 and 2000, lung cancer rates in U.S. men and women aged 35-54 yr have declined. To investigate whether these declines can adequately be explained by changes in smoking prevalence, consumption, and duration, or if changes in tar and nicotine yields also contributed, two model-fitting approaches were used. Both approaches used individual person National Health Interview Survey data on smoking prevalence, age of starting and time of quitting, and national estimates of consumption per smoker and yields. Both approaches compared observed rates (by sex and age) relative to 1985, with those predicted after successively including various smoking variables into the model, making varying allowance for compensation for reduced yield. Approach A was simpler, based on mean smoking statistics estimated separately for current and former smokers. Approach B used the multistage model and individual smoking histories to estimate risk. Both approaches showed observed declines in risk were (except for men aged 35-39 yr) clearly greater than predicted based only on prevalence, consumption, and duration. Including yield generally improved the fit. At younger ages, models assuming substantial compensation (consistent with evidence from studies relating nicotine yield and intake) fitted well, but at age 50-54 yr in both sexes and age 45-49 yr in women, the decline was better fitted by models assuming little compensation. The conclusions were not sensitive to the precise parameter values assumed in the modeling. Interpretation is not straightforward, but the findings suggest declines in yields have contributed to the recent declines in rates in young U.S. men and women.
Inhalation Toxicology 06/2006; 18(5):365-88. · 1.92 Impact Factor
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ABSTRACT: Epidemiological data suggest that smoking filter and lower tar cigarettes is associated with less lung cancer risk than is smoking plain and higher tar cigarettes. A recent National Cancer Institute monograph claimed these apparent benefits of lower delivery products may be illusory if relative risks are adjusted for daily consumption, and switching leads to "compensation" for reduced nicotine intake by increasing numbers of cigarettes smoked. To investigate this, we compared relative risks unadjusted and adjusted for daily cigarette consumption. Overall estimates of the filter/plain relative risk, using random-effects meta-analysis, were 0.61 (95%confidence interval 0.54 to 0.70) for unadjusted data and 0.66 (0.58 to 0.76) for adjusted data. The lower tar/higher tar relative risk was estimated as 0.60 (0.45 to 0.81) for unadjusted data and 0.73 (0.64 to 0.83) for adjusted data. The risk reductions were clearly seen regardless of gender, study location, period, or design, and when only studies providing both unadjusted and adjusted estimates were considered. Whether or not relative risk estimates are adjusted for cigarette consumption is not crucial to the conclusion of a clear advantage to filter cigarettes and tar reduction. Data on "compensation" for amount smoked were reviewed and any increase following switching to reduced-tar-yield cigarettes was shown to be quite small. Other biases in the epidemiology are also discussed, and we conclude that the apparent advantage to reduced-tar-delivery products is real and likely to be a marked underestimate of the reduction in lung cancer risk from lifetime smoking of low-tar cigarettes.
Inhalation Toxicology 12/2004; 16(13):817-33. · 1.92 Impact Factor
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ABSTRACT: Over the period 1951-1995, lung cancer rates in men aged 35-74 yr more than doubled in the United States but declined slightly in the United Kingdom. In women, rates rose about sevenfold in the United States but only about threefold in the United Kingdom. To investigate whether these very different trends in lung cancer risk could be explained by smoking habits, trends in smoking were compared in the two countries and a multistage model was used to predict lung cancer rates from detailed data on age of starting and stopping smoking, amount smoked per smoker, and sales-weighted average tar levels. In both countries, there was a similar switch to filter cigarettes, reduction in tar levels and the average age of starting to smoke, and decline in prevalence of smoking in women aged under 50 yr and in men. Although some differences were evident, most notably in older women where prevalence of smoking and consumption per adult has increased more in the United States, these trends do not appear to explain the markedly different trends in lung cancer, evident in both sexes and all age groups. The multistage analyses confirmed these tentative conclusions-the differing trends in smoking in the two countries could not explain the markedly differing trends in lung cancer. Lung cancer trends in the United Kingdom were found to be clearly more favorable than expected on the basis of smoking trends, while trends in the United States were less favorable. In sensitivity analyses, these conclusions were found not to be materially dependent on the precise methods used, including whether tar reduction was or was not assumed to be beneficial. The explanation for these findings must lie in changes over time, differing in the two countries, in aspects of smoking not considered in these analyses and/or in exposure to other risk factors. Evidence relating to a number of possible such smoking variables (including type of tobacco, curing, use of pesticides and additives, and butt length) or other risk factors (including air pollution, radon, asbestos, obesity, and marijuana) is discussed, but no clear explanation of the findings is offered. Further research is urgently needed to investigate the causes of these apparently anomalous trends in lung cancer and in smoking habits. Criticism is also presented of the views recently expressed by the authors of NCI Monograph 13 that tar reduction has been ineffective in lowering lung cancer risk and that trends in lung cancer in the United States fit in well with trends in smoking habits.
Inhalation Toxicology 09/2003; 15(9):909-49. · 1.92 Impact Factor
