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Carcinogenicity of alcoholic beverages
Abstract
In February, 2007, 26 scientists from 15 countries met at the International Agency for Research on Cancer (IARC) in Lyon, France, to reassess the carcinogenicity of alcoholic beverages and of ethyl carbamate (urethane), a frequent contaminant of fermented foods and beverages. These assessments will be published as volume 96 of the IARC Monographs. This paper reports on the assessment of alcoholic beverages.
... In 1943, Nettleship et al. discovered the potential carcinogenicity of EC, which is a food-borne carcinogen that can cause lymphoma, lung tumors, liver cancer, skin cancer and other diseases. In 2007, the International Agency for Research on Cancer (IARC) classified EC as Class 2A [3]. Therefore, it is of great significance to study the content control of ethyl carbamate in fermented beverage wine. ...
... After activating the strain in YPD liquid medium, the cell concentration reaches 4.47 × 10 8 CFU/mL, inoculated with a 5% (v/v) dosage in YPD medium with different ethanol content (0%, 5%, 7%, 8%, 9%, 10%), different NaCl content (0%, 5%, 10%, 12%, 13%, 14%, 15%) and different pH (3,4,5,6,7,8,9) at 30 • C. The biomass of OD 600 was measured by oscillating culture at 180 r/min for 24 h to explore the tolerance of the strain. (YPD medium with different contents of ethanol, NaCl and pH without added yeast was used as the blank control). ...
Ethyl carbamate (EC) is a natural by-product in the production of fermented food and alcoholic beverages and is carcinogenic and genotoxic, posing a significant food safety concern. In this study, Clavispora lusitaniae Cl-p with a strong EC degradation ability was isolated from Daqu rich in microorganisms by using EC as the sole nitrogen source. When 2.5 g/L of EC was added to the fermentation medium, the strain decomposed 47.69% of ethyl carbamate after five days of fermentation. It was unexpectedly found that the strain had the ability to produce aroma and ester, and the esterification power reached 30.78 mg/(g·100 h). When the strain was added to rice wine fermentation, compared with the control group, the EC content decreased by 41.82%, and flavor substances such as ethyl acetate and β-phenylethanol were added. The EC degradation rate of the immobilized crude enzyme in the finished yellow rice wine reached 31.01%, and the flavor substances of yellow rice wine were not affected. The strain is expected to be used in the fermented food industry to reduce EC residue and improve the safety of fermented food.
... Alcohol is neurotoxic and several studies have demonstrated the short-and long-term effects of excessive alcohol consumption on brain function and its related pathologies (Brewer and Perrett 1971;Montoliu et al. 1994;Paul et al. 2008;Spear 2018). Alcohol is considered a carcinogen by the International Agency for Research on Cancer, and epidemiologic studies have suggested its relation to increased risk of several types of cancer (Baan et al. 2007). The first metabolite of ethanol, acetaldehyde, has a major role in the tumor-promoting effect of ethanol and can cause the impairment of DNA synthesis and repair and leads to DNA hypomethylation (Pöschl et al. 2004), facilitation of cellular entry for other carcinogens, and induction of carcinogen-activating enzymes (Anderson et al. 1995;Lieber et al. 1979;Mufti et al. 1989). ...
... The carcinogens which increased the risk of BTs were discussed including 1. NOCs which have been considered as the most potent nervous system carcinogens, especially in childhood brain tumor (CBT) (Preston-Martin et al. 1982). 2. Alcohol which is considered a carcinogen and epidemiologic studies have suggested that it is related to an increased risk of several types of cancer (Baan et al. 2007). Its carcinogenic property is due to the impairment of DNA synthesis, DNA repair, and DNA hypomethylation (Pöschl et al. 2004). ...
CNS tumors are a diverse group of neoplasms that emerge from a variety of different CNS cell types. These tumors may be benign, malignant, or borderline in nature. The majority of high grade glial tumors are fatal, with the exception of pilocytic astrocytoma. Primary malignant CNS tumors occur at a global annual rate of 2.1 to 5.8 per 100,000 persons. Males are more likely to develop malignant brain tumors than females, whereas benign meningiomas are more common in adult females. Additionally, gender inequalities in non-malignant tumors peak between the ages of 25 and 29 years. Only a small number of genetic variants have been associated with survival and prognosis. Notably, central nervous system (CNS) tumors exhibit significant age, gender, and race variation. Race is another factor that affects the incidence of brain and spinal cord tumors. Different races exhibit variation in terms of the prevalence of brain and CNS malignancies. This chapter discusses ongoing research on brain and spinal cord tumor epidemiology, as well as the associated risks and accompanied disorders.KeywordsEpidemiologyBrain tumorsGliomaGlioblastomaNeurological Surgery
... However, alcoholrelated carcinogenesis is not liver-centered and tumor in the oral cavity, pharynx, larynx, esophagus and colorectum, and breast cancer have been also associated to alcohol intake. 132,133 Importantly, the beneficial effects of alcohol consumption have exclusively been attributed to moderate consumption, usually defined as 1 ---2 servings/day or 14---28 g of alcohol 131 ; however, those doses have recently been challenged as detrimental. 134 These supposedly 'healthy' effects have been related to the antiinflammatory, antioxidant and hypotensive properties of several components of alcoholic beverages (polyphenols, xanthohumol). ...
... [22] Alcohol increases the cancer risk and accounts for 4% of cancer deaths. [24][25][26] Furthermore, lifestyle factors and diet have metabolic consequences (such as inflammation) that increase the chance of developing cancer. [22] The chance of some cancers, especially colon, esophagus, and uterus cancer, increases with overweight and obesity. ...
... Both our study and that of Fang et al. adjusted for age and gender, which are major confounders in the cancer/ suicide association. Fang et al. also adjusted their models for cohabitation status, socioeconomic status, and educational level, but did not adjust for other major confounders in the cancer/suicide association, such as alcohol consumption [27,49]. ...
Background
Mortality data obtained from death certificates have been studied to explore causal associations between diseases. However, these analyses are subject to collider and reporting biases (selection and information biases, respectively). We aimed to assess to what extent associations of causes of death estimated from individual mortality data can be extrapolated as associations of disease states in the general population.
Methods
We used a multistate model to generate populations of individuals and simulate their health states up to death from national health statistics and artificially replicate collider bias. Associations between health states can then be estimated from such simulated deaths by logistic regression and the magnitude of collider bias assessed. Reporting bias can be approximated by comparing the estimates obtained from the observed death certificates (subject to collider and reporting biases) with those obtained from the simulated deaths (subject to collider bias only). As an illustrative example, we estimated the association between cancer and suicide in French death certificates and found that cancer was negatively associated with suicide. Collider bias, due to conditioning inclusion in the study population on death, increasingly downwarded the associations with cancer site lethality. Reporting bias was much stronger than collider bias and depended on the cancer site, but not prognosis.
Results
The magnitude of the biases ranged from 1.7 to 9.3 for collider bias, and from 4.7 to 64 for reporting bias.
Conclusions
These results argue for an assessment of the magnitude of both collider and reporting biases before performing analyses of cause of death associations exclusively from mortality data. If these biases cannot be corrected, results from these analyses should not be extrapolated to the general population.
... Besides the many lifestyle factors associated with risk of CRC [76][77][78][79][80][81][82][83][84][85][86], we found a positive association between the frequency of more than one bowel movement per day (compared with once per day) and the CRC risk in the Chinese population. Studies on the association between bowel frequency and CRC risk have not yielded consistent results [87][88][89][90]. ...
Background
Due to their known variation by geography and economic development, we aimed to evaluate the incidence and mortality of colorectal cancer (CRC) in China over the past decades and identify factors associated with CRC among the Chinese population to provide targeted information on disease prevention.
Methods
We conducted a systemic review and meta-analysis of epidemiolocal studies on the incidence, mortality, and associated factors of CRC among the Chinese population, extracting and synthesising data from eligible studies retrieved from seven global and Chinese databases. We pooled age-standardised incidence rates (ASIRs) and mortality rates (ASMRs) for each province, subregion, and the whole of China, and applied a joinpoint regression model and annual per cent changes (APCs) to estimate the trends of CRC incidence and mortality. We conducted random-effects meta-analyses to assess the effect estimates of identified associated risk factors.
Results
We included 493 articles; 271 provided data on CRC incidence or mortality, and 222 on associated risk factors. Overall, the ASIR of CRC in China increased from 2.75 to 19.39 (per 100 000 person-years) between 1972 and 2019 with a slowed-down growth rate (APC1 = 5.75, APC2 = 0.42), while the ASMR of CRC decreased from 12.00 to 7.95 (per 100 000 person-years) between 1974 and 2020 with a slight downward trend (APC = -0.89). We analysed 62 risk factors with synthesized data; 16 belonging to the categories of anthropometrics factors, lifestyle factors, dietary factors, personal histories and mental health conditions were graded to be associated with CRC risk among the Chinese population in the meta-analysis limited to the high-quality studies.
Conclusions
We found substantial variation of CRC burden across regions and provinces of China and identified several associated risk factors for CRC, which could help to guide the formulation of targeted disease prevention and control strategies.
Registration
PROSPERO: CRD42022346558.
... Alcohol has been associated with an increased risk of several cancers, including female breast cancer [43,44]. In the Million Women Study, with over 68 000 cases, there was a 12% increase in risk per 10 g/day increment in alcohol intake [44]. ...
Background
The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes.
Methods
We investigated cross-sectional associations between self-reported alcohol intake and serum or plasma concentrations of oestradiol, oestrone, progesterone (in pre-menopausal women only), testosterone, androstenedione, DHEAS (dehydroepiandrosterone sulphate) and SHBG (sex hormone binding globulin) in 45 431 pre-menopausal and 173 476 post-menopausal women. We performed multivariable linear regression separately for UK Biobank, EPIC (European Prospective Investigation into Cancer and Nutrition) and EHBCCG (Endogenous Hormones and Breast Cancer Collaborative Group), and meta-analysed the results. For testosterone and SHBG, we also conducted two-sample Mendelian Randomization (MR) and colocalisation using the ADH1B (Alcohol Dehydrogenase 1B) variant (rs1229984).
Results
Alcohol intake was positively, though weakly, associated with all hormones (except progesterone in pre-menopausal women), with increments in concentrations per 10 g/day increment in alcohol intake ranging from 1.7% for luteal oestradiol to 6.6% for post-menopausal DHEAS. There was an inverse association of alcohol with SHBG in post-menopausal women but a small positive association in pre-menopausal women. MR identified positive associations of alcohol intake with total testosterone (difference per 10 g/day increment: 4.1%; 95% CI: 0.6%, 7.6%) and free testosterone (7.8%; 4.1%, 11.5%), and an inverse association with SHBG (-8.1%; -11.3%, -4.9%). Colocalisation suggested a shared causal locus at ADH1B between alcohol intake and higher free testosterone and lower SHBG (PP4: 0.81 and 0.97 respectively).
Conclusions
Alcohol intake was associated with small increases in sex hormone concentrations, including bioavailable fractions, which may contribute to its effect on breast cancer risk.
... This could explain the threefold increase in incidence rates of laryngeal cancer in women observed in our study. In addition to tobacco, alcohol consumption has been identified as a risk factor for laryngeal cancer in Western studies (40,41). Meanwhile, indoor air pollution is a more significant risk factor in developing countries. ...
Objectives: Laryngeal cancer accounts for about 1 to 2 % of all cancers; this incidence rate depends on the geographical region and ethnicity. Due to the lack of a comprehensive epidemiological study on laryngeal cancer in recent years, we designed this study to investigate the incidence and geographical distribution of laryngeal cancer in Iran from 2004 to 2014. Methods: the data collected from the Iranian national Cancer data System registry, all the cases of laryngeal cancer (with topography code 32 and histology of laryngeal cancer) have been retrieved and analyzed from a comprehensive cancer database during the 11 years. Then statistical data were analyzed by SPSS, version 16. Results: During the 11-year study, 13,241 new cases of laryngeal cancer were recorded, of which 11454 were men (86%) and 1788 were women (14%). According to this assessment, North Khorasan, Sistan and Baluchestan, and East Azerbaijan provinces had the highest growth rate, and North Khorasan, Gilan, and Kerman provinces with the highest incidence rates of 4.44, 3.29, and 2.23 per 100,000 respectively, between 2004 and 2014. Conclusion: According to the results of this study, the incidence rate of laryngeal cancer, especially in women, is increasing in Iran. Further studies are needed to investigate the causes of increased incidence.
... Alcohol consumption is closely associated with the development of head and neck squamous cell carcinoma (HNSCC) [1][2][3]. Many previous case-control studies and prospective research works reported that a certain amount of daily alcohol intake increases the risk of cancer in the oral cavity, pharynx, larynx, and esophagus [4,5]. The International Agency for Research on Cancer (IARC) concluded that alcohol was confirmed as a causative factor in the development of oral cavity, pharynx, larynx, esophagus, breast, liver, and colon cancer [4]. ...
Background:
Head and neck squamous cell carcinoma (HNSCC) is closely associated with alcohol consumption and individual genetic susceptibility, such as single nucleotide polymorphism (SNP) of alcohol dehydrogenase (ADH). This study aimed to investigate the association of ADH7 SNPs with the risk of HNSCC.
Methods:
We analyzed ADH7 rs1573496C>G, rs3737482T>C, rs1154460G>A, and rs284787T>C SNPs in 250 patients with HNSCC and 322 controls in the Korean populations. Genotyping was conducted using the TaqMan assay. Linkage disequilibrium and haplotypes were analyzed.
Results:
The odds ratios (OR) and 95% confidence intervals (CI) of the CT and CC genotypes of ADH7 rs3737482T>C were 0.48 (0.29-0.78) and 0.69 (0.49-0.96), indicating a significantly decreased risk. In SNP of rs1154460G>A, the OR and 95% CI of the AA genotype was 1.63 (1.11-2.40), showing a significant increase in the risk. Furthermore, SNPs of ADH7 rs3737482T>C and ADH7 rs1154460G>A exhibit synergistic interactions with alcohol composition on the risk of HNSCC. None of the haplotypes were associated with the risk of HNSCC.
Conclusions:
ADH7 rs3737482T>C and rs1154460G>A SNPs are associated with the risk of development of HNSCC in Koreans. They could serve as molecular biological markers to screen high-risk groups for HNSCC.
... A Monograph Working Group of the IARC in 2007 declared that alcoholic beverages were carcinogenic (Baan et al., 2007), although the exact causative mechanisms remain unclear. Current hypotheses of cancer-causing mechanisms include ethanol's impairment of tumor cell destruction by natural killer cells, activation of cell proliferation related to estrogen, and the carcinogenic effects of alcohol metabolites such as acetaldehyde and oxygen reactive species (García-Quiroz et al., 2017;Rumgay et al., 2021). ...
Alcohol consumption is associated with an increased risk of breast cancer, even at low alcohol intake levels, but public awareness of the breast cancer risk associated with alcohol intake is low. Furthermore, the causative mechanisms underlying alcohol's association with breast cancer are unknown. The present theoretical paper uses a modified grounded theory method to review the research literature and propose that alcohol's association with breast cancer is mediated by phosphate toxicity, the accumulation of excess inorganic phosphate in body tissue. Serum levels of inorganic phosphate are regulated through a network of hormones released from the bone, kidneys, parathyroid glands, and intestines. Alcohol burdens renal function, which may disturb the regulation of inorganic phosphate, impair phosphate excretion, and increase phosphate toxicity. In addition to causing cellular dehydration, alcohol is an etiologic factor in nontraumatic rhabdomyolysis, which ruptures cell membranes and releases inorganic phosphate into the serum, leading to hyperphosphatemia. Phosphate toxicity is also associated with tumorigenesis, as high levels of inorganic phosphate within the tumor microenvironment activate cell signaling pathways and promote cancer cell growth. Furthermore, phosphate toxicity potentially links cancer and kidney disease in onco-nephrology. Insights into the mediating role of phosphate toxicity may lead to future research and interventions that raise public health awareness of breast cancer risk and alcohol consumption.
... Alcohol is metabolized by alcohol dehydrogenase to a toxic and reactive metabolite, acetaldehyde, which is further oxidized to acetate, mainly by aldehyde dehydrogenase 2 (ALDH2), an enzyme present in the mitochondrial matrix of cells [19]. Acetaldehyde derived from alcohol can cause DNA mutation and cellular damage [20,21] and impairs axonal transport and cytoskeletal properties in the nervous system [22]. A common Asian-specific ALDH2 single nucleotide polymorphism (SNP), rs671 (G to A nucleotide change), results in an amino acid substitution from glutamic acid to lysine at position 504 (Glu504Lys) and causes a dramatic loss of ALDH2 enzyme activity and accumulation of acetaldehyde level after alcohol consumption, with manifestation of facial flushing, palpitations, nausea, muscle weakness and headache [23]. ...
Neurofilament light chain (NFL), as a measure of neuroaxonal injury, has recently gained attention in alcohol dependence (AD). Aldehyde dehydrogenase 2 (ALDH2) is the major enzyme which metabolizes the alcohol breakdown product acetaldehyde. An ALDH2 single nucleotide polymorphism (rs671) is associated with less ALDH2 enzyme activity and increased neurotoxicity. We examined the blood NFL levels in 147 patients with AD and 114 healthy controls using enzyme-linked immunosorbent assay and genotyped rs671. We also followed NFL level, alcohol craving and psychological symptoms in patients with AD after 1 and 2 weeks of detoxification. We found the baseline NFL level was significantly higher in patients with AD than in controls (mean ± SD: 264.2 ± 261.8 vs. 72.1 ± 35.6 pg/mL, p < 0.001). The receiver operating characteristic curve revealed that NFL concentration could discriminate patients with AD from controls (area under the curve: 0.85; p < 0.001). The NFL levels were significantly reduced following 1 and 2 weeks of detoxification, with the extent of reduction correlated with the improvement of craving, depression, and anxiety (p < 0.001). Carriers with the rs671 GA genotype, which is associated with less ALDH2 activity, had higher NLF levels either at baseline or after detoxification compared with GG carriers. In conclusion, plasma NFL level was increased in patients with AD and reduced after early abstinence. Reduction in NFL level corroborated well with the improvement of clinical symptoms. The ALDH2 rs671 polymorphism may play a role in modulating the extent of neuroaxonal injury and its recovery.
... Based on the current articles, no carob-based fermented vegetable beverages without alcohol, yeast or animal products have been developed, so it would be interesting to consider the development of a fermented beverage free of animal products and low in alcohol beverages. Despite the fact that the consumption of alcoholic beverages is present in many gastronomic cultures, ethanol is classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC), and therefore, there is no safe minimum level that is not 0 [61]. The consumption of non-alcoholic beverages is also suitable for children, elderly and pregnant women. ...
Rice, tiger nut and carob are Mediterranean products suitable for developing new foods, such as fermented beverages, due to their nutritional properties. These crops have a high carbohydrate content, are gluten and lactose-free and have a low allergenicity index. The development of fermented beverages from these crops can contribute to the Sustainable Development Goals by promoting human health and sustainable production and consumption. A narrative review of the nutritional value and potential functional activity of fermented beverages made from these crops was carried out. This literature review of existing studies on fermented and non-fermented beverages highlights their composition, production methodology, and health benefits. Fermented beverages made from these crops are high in fiber, essential fatty acids, vitamins (group B), and minerals. Fermentation increases the bioaccessibility of these nutrients while decreasing possible anti-nutritional factors. These fermented beverages offer several health benefits due to their antioxidant effects, modulating the intestinal microbiota and reducing the incidence of chronic degenerative diseases such as metabolic syndrome. Therefore, fermented rice, tiger nut and carob beverages can improve the Spanish diet by offering improved nutritional value and beneficial health effects. Additionally, these local crops promote sustainability, making them an appropriate choice for developing new fermented beverages.
... Overall, regardless of the variety of beverages, ethanol intake accounts for an estimated 5% of total cancers, predominantly of the liver [76], upper respiratory tract, gastrointestinal tract, pancreas, breast, and lung [38,77]. Jayasekara et al. reported that their findings support dose-dependent associations linking chronic alcohol use with cancers such as breast, upper respiratory tract, digestive tract, and colorectal carcinoma [78]. ...
In our recent article (Smędra et al.: Oral form of auto-brewery syndrome. J Forensic Leg Med. 2022; 87: 102333), we showed that alcohol production can occur in the oral cavity (oral auto-brewery syndrome) due to a disruption in the microbiota (dysbiosis). An intermediate step on the path leading to the formation of alcohol is acetaldehyde. Typically, acetic aldehyde is transformed into acetate particles inside the human body via acetaldehyde dehydrogenase. Unfortunately, acetaldehyde dehydrogenase activity is low in the oral cavity, and acetaldehyde remains there for a long time. Since acetaldehyde is a recognised risk factor for squamous cell carcinoma arising from the oral cavity, we decided to analyse the relationship linking the oral microbiome, alcohol, and oral cancer using the narrative review method, based on browsing articles in the PubMed database. In conclusion, enough evidence supports the speculation that oral alcohol metabolism must be assessed as an independent carcinogenic risk. We also hypothesise that dysbiosis and the production of acetaldehyde from non-alcoholic food and drinks should be treated as a new factor for the development of cancer.
... Alcohol consumption is also an important risk factor for tumor development; according to WHO data, 3.5% of all cancer-related deaths are related to chronic alcohol drinking [14]. Alcohol can induce carcinogenesis in numerous organs, including the upper aerodigestive tract, liver, colorectum, female breast, etc. [15]. However, there are few reports on whether alcohol consumption is carcinogenic to cervical cancer [16,17]. ...
Cervical cancer causes malignant tumors in females and threatens the physical and mental health of women. Current research shows that persistent infection of high-risk HPV is the main cause of cervical cancer. However, not all cervical cancer is caused by HPV infection, which may also be related to other factors, such as nutritional status and lifestyle. This study focuses on the effect of alcohol consumption on the methylation status of cervical cancer from the perspective of methyl donors. We established a mouse tumor-bearing model with cervical cancer SiHa cells, and at the same time, we cultured SiHa cells in vitro. Different concentrations of ethanol were administered to the model mice and SiHa cells. Then, we detected the levels of the methyl-donor folate and methionine and their metabolite homocysteine levels in mice serum, tumor tissues, and SiHa cells. Furthermore, we determined the expression of the members of the DNA methyltransferase family (DNMT1, DNMT3a, and DNMT3b) in tumor tissue by immunohistochemistry. qRT-PCR and Western blotting analysis were used to detect the mRNA and protein levels of members of the DNA methyltransferase family in cervical cancer SiHa cells. Our results show that the levels of the methyl donor (folate and methionine) decreased with the increase of ethanol concentration (p < 0.05), and the homocysteine level increased significantly (p < 0.05). In SiHa cells, the mRNA and protein levels of the DNMT family members and their receptors were significantly higher than those in the control group (p < 0.05). Collectively, these results suggest that ethanol could influence DNMT expression by inducing methyl donor consumption, thereby causing cervical cancer cells to exhibit genome-wide hypomethylation.
... Alcoholic beverages are recognized as carcinogenic for humans and ethanol can cross the placental barrier in pregnant women (Baan et al., 2007). Furthermore, acetaldehyde, its metabolite, could exert a mutagenic activity in the fetus (Lachenmeier and Sohnius, 2008). ...
Childhood cancer incidence is known to vary by age, sex, and race/ethnicity, but evidence is limited regarding external risk factors. We aim to identify harmful combinations of air pollutants and other environmental and social risk factors in association with the incidence of childhood cancer based on 2003-2017 data from the Georgia Cancer Registry. We calculated the standardized incidence ratios (SIR) of Central Nervous System (CNS) tumors, leukemia and lymphomas based on age, gender and ethnic composition in each of the 159 counties in Georgia, USA. County-level information on air pollution, socioeconomic status (SES), tobacco smoking, alcohol drinking and obesity were derived from US EPA and other public data sources. We applied two unsupervised learning tools (self-organizing map [SOM] and exposure-continuum mapping [ECM]) to identify pertinent types of multi-exposure combinations. Spatial Bayesian Poisson models (Leroux-CAR) were fit with indicators for each multi-exposure category as exposure and SIR of childhood cancers as outcomes. We identified consistent associations of environmental (pesticide exposure) and social/behavioral stressors (low socioeconomic status, alcohol) with spatial clustering of pediatric cancer class II (lymphomas and reticuloendothelial neoplasms), but not for other cancer classes. More research is needed to identify the causal risk factors for these associations.
... Exposure to carcinogens that are produced by environmental pollution or through lifestyle habits such as tobacco smoking and excessive alcohol consumption, and its association with an increased risk of developing HNCs, have been widely studied [58][59][60][61]. Nitrosamines and polycyclic aromatic hydrocarbons (PAHs) that are formed during tobacco smoking, as well as acetaldehyde production and cytochrome p450 2E1 (CYP2E1) enzyme induction by alcohol consumption, contribute to the formation of persistent DNA adducts, which disrupt the DNA double helix and lead to the formation of hypermutations and chromosomal instability [62][63][64][65][66][67]. Smoking has also been implicated in the dysregulation of antitumor immune mechanisms, and particularly in the impairment of T-cell-mediated immune responses in patients with esophageal squamous cell carcinoma (ESCC) [68]. ...
Head and neck cancer (HNC) is a term collectively used to describe a heterogeneous group of tumors that arise in the oral cavity, larynx, nasopharynx, oropharynx, and hypopharynx, and represents the sixth most common type of malignancy worldwide. Despite advances in multimodality treatment, the disease has a recurrence rate of around 50%, and the prognosis of metastatic patients remains poor. HNCs are characterized by a high degree of genomic instability, which involves a vicious circle of accumulating DNA damage, defective DNA damage repair (DDR), and replication stress. Nonetheless, the damage that is induced on tumor cells by chemo and radiotherapy relies on defective DDR processes for a successful response to treatment, and may play an important role in the development of novel and more effective therapies. This review summarizes the current knowledge on the genes and proteins that appear to be deregulated in DDR pathways, their implication in HNC pathogenesis, and the rationale behind targeting these genes and pathways for the development of new therapies. We give particular emphasis on the therapeutic targets that have shown promising results at the pre-clinical stage and on those that have so far been associated with a therapeutic advantage in the clinical setting.
... Alcoholic beverages are classified as group I carcinogens that significantly increase the risk of cancer at various sites. 1 The process from the initiation of alcohol consumption to cancer development progresses over the long term. Alcohol consumption can lead to disorders and diseases that could play a mediating role in the association between alcohol consumption and cancer risk, owing to sharing the same risk factors (e.g., alcohol consumption and smoking). ...
Aim:
To estimate the risk of cancer incidence and mortality among patients with alcoholic liver disease in South Korea.
Methods:
A matched cohort study was conducted, including 1,042,185 men (alcoholic liver disease cases: 208,437; controls: 833,748) and 100,400 women (alcoholic liver disease cases: 20,080; controls: 80,320), matched for sex, age, smoking, alcohol consumption, and body mass index at a 1:4 ratio. The risk of cancer incidence and mortality in the alcoholic liver disease group was assessed using Cox proportional hazards regression models.
Results:
Both men and women with alcoholic liver disease had an elevated risk of all-cancer and liver cancer incidence and mortality in comparison with the control group. In men, alcoholic liver disease was associated with a significantly higher risk of development of 10 cancer types, including lip, oral cavity, and pharynx; esophagus; liver; gallbladder and biliary tract; pancreas; larynx; lung; kidney; thyroid gland; and leukemia. Subgroup analysis by hepatitis B and C infection showed increased hazard ratios of all cancer incidences and mortality in the alcoholic liver disease group, regardless of hepatitis B or C infection status. In both sexes, a higher number and more years of hospital or clinic visits for alcoholic liver disease were associated with an increased risk of incidence and mortality from all cancers and liver cancer. A more profound dose-response relationship between alcoholic liver disease and alcohol consumption was observed in women than in men.
Conclusions:
Our findings emphasize the need for a clinical surveillance program and the early detection of cancer in patients with alcoholic liver disease.
... For example, while 94.8% of Canadian smokers were aware that smoking leads to lung cancer, only 25% of Canadians surveyed outside liquor stores knew that alcohol could lead to cancer [3,4]. Other health effects of alcohol include liver, heart, neuropsychiatric, and metabolic disease, with no established safe limit to consumption [5,6]. Despite these adverse outcomes, alcohol consumption continues to rise, partly due to the COVID-19 pandemic leading to social isolation and increased availability of alcohol from extended hours of sale, home delivery, and reduced minimum pricing in some provinces [7,8]. ...
Background:
Compared to other recreational substances in Canada, alcohol consumption incurs the highest healthcare costs. Liver transplant recipients are unique stakeholders as members of the general public with lived experiences of liver disease. We sought to explore their perspectives on the current state of public education on alcohol-related health effects.
Methods:
The most recent 400 liver transplant recipients at Vancouver General Hospital, Canada, were invited to participate in an anonymous online survey on alcohol-related health effects by mail, email, and phone.
Results:
Of 372 contacted patients, 212 (57%) completed the survey. Most patients were between 60-79 years, 63% were male, and 69% were Caucasian. The most common liver conditions leading to transplant were viral hepatitis (33%), alcohol-related liver disease (16%), autoimmune liver disease (14%), and non-alcoholic fatty liver disease (15%). Most patients knew that alcohol leads to liver failure (85%), but fewer knew about alcohol leading to cancer (54%), heart disease (50%), and damage to other organs (58%). Most common sources of information included public media (61%), family and friends (52%), and physicians (49%), with narrative comments about learning of alcohol-related health effects after liver diagnosis. Most patients believed that public health education at a middle/high school level would have long-term efficacy (72%) compared to health warning labels (33%) and safety messaging in commercials (39%). Current public education was felt to be adequate by only 20% of patients and 73% of patients supported health warning labels.
Conclusions:
Liver transplant patients reported a high, but not universal, awareness of alcohol-related health effects. A majority thought that current public health efforts were inadequate; it is critical to implement public health interventions to ensure consumers are able to make an informed decision on alcohol consumption.
... In our study, we showed that alcoholic psychoses, alcohol dependence and CVD (IHD, stroke) were significantly related, but alcohol abuse was not significantly related to CVD (IHD, stroke), which we believe is because alcohol abuse is likely to cause death before CVD is diagnosed. Furthermore, the overall risk-benefit relationship of any form of alcohol consumption on an individual level must be judged cautiously in light of the well-known detrimental effects of alcohol use on other disease outcomes, such as injuries and cancer [3,14,15]. Hence, making recommendations for clinical practice is challenging because of the simultaneous beneficial and detrimental effects of, on average, low alcohol consumption, and because evidence from randomized controlled trials on the long-term effects of alcohol consumption is lacking. This has been confirmed in our study that chronic diseases are positively correlated in patients with AUD. ...
The complex effects of alcohol consumption on the cardiovascular system vary with mean daily consumption and duration of intake. This population-based retrospective cohort study aimed to explore the risk of cardiovascular disease (CVD) in patients with alcohol use disorder (AUD). Data was collected from the Taiwan National Health Insurance Research Database from 2000 to 2013. A total of 7,420 patients with AUD were included in our study group, and 29,680 age- and sex-matched controls without AUD in the control group. Cox proportional hazard regression analysis was used to investigate the effects of AUD on the risk of CVD. Most patients were men aged 25–44 years. At the end of the follow-up period, the AUD group had a significantly higher incidence of CVD (27.39% vs. 19.97%, P<0.001) and more comorbidities than the control group. The AUD group also exhibited a significantly higher incidence of CVD than the control group based on the Cox regression analysis and Fine and Gray’s competing risk model (adjusted hazard ratio [AHR] = 1.447, 95% confidence interval [CI] = 1.372–1.52 5, P<0.001). Furthermore, male sex, diabetes mellitus, hypertension, hyperlipidemia, chronic kidney disease, chronic obstructive pulmonary disease, anxiety, depression, and a high Charlson Comorbidity Index were also associated with an increased risk of CVD. Patients with AUD in different CVD subgroups, such as those with CVD, ischemic heart disease (IHD), and stroke, were at a significantly higher risk of disease than those without AUD; CVD (AHR = 1.447, 95% CI = 1.372–1.525, P<0.001), IHD (AHR = 1.304, 95% CI = 1.214–1.401, P<0.001), and stroke (AHR = 1.640, 95% CI = 1.519–1.770, P<0.001). The risk also significantly differed among patients in the different CVD subgroups. We observed an association between AUD and development of CVD even after adjusting for several comorbidities and medications in our nationwide population cohort.
Background
Tobacco contains harmful carcinogens that have been associated with cancers. Some studies have associated tobacco smoking with prostate cancer (PCa). The relationship between alcohol consumption as a risk factor for prostate cancer has been debated. Some studies associated alcohol consumption with increased risk of PCa, associating alcohol consumption with higher-grade cancers and poorer prognosis. Other studies have found a minimal relationship with PCa, with some even suggesting that alcohol consumption may even be protective. This study evaluates the association between smoking and alcohol consumption in prostate cancer patients.
Methodology
This is a retrospective study on one hundred and fifty-two patients diagnosed with prostate cancer with a known history of both smoking and or alcohol consumption managed over a 9year period from January 2012 to December 2020 from three Urology referrals hospitals. Patients with incomplete history were excluded. Their data such as age, a history of cigarette smoking, prostate-specific antigen level, prostate biopsy histopathology reports, and Gleason’s grade were extracted. This was coded into Microsoft Excel and analyzed with SPSS version 20. The results were analyzed and presented in tables and charts.
Results
One hundred and thirty-five patients had a premorbid history of smoking and alcohol consumption with a mean age of 69 years and a modal age in the 70–79-year age group. Fifty-three (39.3%) of the patients had a history of cigarette smoking, ninety-four (69.6%) had a history of alcohol consumption. In comparison, fifty-one (37.8%) had a history of cigarette smoking and alcohol consumption. The high-risk Gleason's 8-10 prostate cancer was commoner among smokers than nonsmokers. There was no statistically significant association between cigarette smoking and alcohol consumption alone and combined with PCa.
Conclusion
The high-risk Gleason's 8-10 prostate cancer was commoner among smokers than nonsmokers. There was no statistically significant association between cigarette smoking and alcohol consumption and the risk of prostate cancer.
Background: The gene variants ADH1B*2 (Arg48His, rs1229984) and ALDH2*2 (Glu504Lys, rs671) are common in East Asian populations but rare in other populations. We propose that selective pressures from pathogen exposure and dietary changes during the neolithic transition favored these variants. Thus, their current association with differences in alcohol sensitivity likely results from phenotypic plasticity rather than direct natural selection.
Methods: Samples sourced from the Allele Frequency Database (ALFRED) were utilized to compute the average frequency of ADH1B*2 and ALDH2*2 across 88 and 61 countries, respectively. Following computation of the average national allele frequencies, we tested the significance of their correlations with ecological variables. Subsequently, we subjected them to Principal Component Analysis (PCA) and Elastic Net regularization. For comprehensive evaluation, we collected individual-level phenotypic associations, compiling a Phenome-Wide Association Study (PheWAS) spanning multiple ethnicities.
Results: Following multiple testing correction, ADH1B*2 displayed significant correlations with Neolithic transition timing (r = 0.405, p.adj = 2.013e-03, n = 57) and historical trypanosome burden (r = -0.418, p.adj = 0.013, n = 57). The first two components of PCA explained 47.7% of the total variability across countries, with the top three contributors being the historical indices of population density and trypanosome and leprosy burdens. Historical burdens of the Mycobacteria tuberculosis and leprosy were the sole predictive variables with positive coefficients that survived Elastic Net regularization.
Conclusions: Our analyses suggest that Mycobacteria may have played a role in the joint selection of ADH1B*2 and ALDH2*2, expanding the "toxic aldehyde hypothesis" to include Mycobacterium leprae. Additionally, our hypothesis, linked to dietary shifts from rice domestication, emphasizes nutritional deficiencies as a key element in the selective pressure exerted by Mycobacteria. This offers a plausible explanation for the high frequency of ADH1B*2 and ALDH2*2 in Asian populations.
Background
Unhealthy alcohol consumption is a severe public health problem. But low to moderate alcohol consumption is associated with high subjective well-being, possibly because alcohol is commonly consumed socially together with friends, who often are important for subjective well-being. Disentangling the health and social complexities of alcohol behavior has been difficult using traditional rating scales with cross-section designs. We aim to better understand these complexities by examining individuals’ everyday affective subjective well-being language, in addition to rating scales, and via both between- and within-person designs across multiple weeks.
Method
We used daily language and ecological momentary assessment on 908 US restaurant workers (12692 days) over two-week intervals. Participants were asked up to three times a day to “describe your current feelings”, rate their emotions, and report their alcohol behavior in the past 24 hours, including if they were drinking alone or with others.
Results
Both between and within individuals, language-based subjective well-being predicted alcohol behavior more accurately than corresponding rating scales. Individuals self-reported being happier on days when drinking more, with language characteristic of these days predominantly describing socializing with friends. Between individuals (over several weeks), subjective well-being correlated much more negatively with drinking alone ( r = -.29) than it did with total drinking ( r = -.10). Aligned with this, people who drank more alone generally described their feelings as sad , stressed and anxious and drinking alone days related to nervous and annoyed language as well as a lower reported subjective well-being.
Conclusions
Individuals’ daily subjective well-being, as measured via language, in part, explained the social aspects of alcohol drinking. Further, being alone explained this relationship, such that drinking alone was associated with lower subjective well-being.
This chapter reviews both linear and branched monohydric aliphatic C 1 to C 6 alcohols. The C 7 to C 20 monohydric alcohols are covered in Chapter 74. The low‐molecular‐weight alcohols, including methanol, ethanol, 1‐propanol, and isopropanol, are used extensively in industry. These alcohols exist as volatile liquids at ambient temperatures, and exposure can occur in both industrial and nonindustrial environments. The C 1 to C 6 monohydric alcohols are flammable, but not reactive. The health effects in laboratory animals and in humans for the C 1 to C 6 alcohols are reviewed, as well as workplace exposure methods and biomonitoring and/or biomarker information.
Codzienny styl życia oraz sposób odżywiania wpływają na kondycję psychofizyczną organizmu. Palenie tytoniu zwiększa ryzyko raka krtani. Może zwiększać ryzyko wystąpienia refluksu krtaniowo‑gardłowego oraz obrzęku Reinkego. Nadmierne spożycie napojów wysokoprocentowych skutkować może odwodnieniem błon śluzowych organizmu oraz zmianami barwy głosu. Publikacje naukowe nie potwierdzają jednoznacznego szkodliwego wpływu kofeiny na narząd głosu. Szkodliwość ta może wynikać z ilości przyjmowanej kofeiny. Odwodnienie organizmu ma szkodliwy wpływ na aerodynamiczne i akustyczne pomiary fonacji. Zbyt niska podaż wody w ciągu dnia może prowadzić do obniżonego nawilżenia błon śluzowych jamy ustnej, gardła oraz krtani. Osoby przyjmujące małą ilość płynów w ciągu dnia mogą odczuwać nadmierną suchość w jamie ustnej, bóle gardła czy chrypkę. Dieta wspierająca prawidłową pracę narządu głosu powinna być dietą zbilansowaną, spełniającą dzienne zapotrzebowanie kaloryczne oraz witaminowo‑mineralne. Jednym z najkorzystniejszych modeli diety, o prozdrowotnych właściwościach jest dieta śródziemnomorska. Spośród ziół i przypraw wykazujących pozytywny wpływ na błony śluzowe narządów uczestniczących w emisji głosu wymienia się m.in. nagietka lekarskiego, tymianek właściwy, imbir lekarski oraz czarnuszkę siewną. Celem artykułu jest podkreślenie wpływu diety i jej poszczególnych elementów oraz stylu życia na głos.
Although ethanol is a class I carcinogen and is linked to more than 700,000 cancer incidences, a clear understanding of the molecular mechanisms underlying ethanol-related carcinogenesis is still lacking. Further understanding of ethanol-related cell damage can contribute to reducing or treating alcohol-related cancers. Here, we investigated the effects of both short- and long-term exposure of human laryngeal epithelial cells to different ethanol concentrations. RNA sequencing shows that ethanol altered gene expression patterns in a time- and concentration-dependent way, affecting genes involved in ribosome biogenesis, cytoskeleton remodeling, Wnt signaling, and transmembrane ion transport. Additionally, ethanol induced a slower cell proliferation, a delayed cell cycle progression, and replication fork stalling. In addition, ethanol exposure resulted in morphological changes, which could be associated with membrane stress. Taken together, our data yields a comprehensive view of molecular changes associated with ethanol stress in epithelial cells of the upper aerodigestive tract.
Background
We examined associations between adherence to adaptations of the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations and total, exposure-related and site-specific cancer risk.
Methods
A total of 20,001 participants ages 40 to 69 years at enrollment into the Melbourne Collaborative Cohort Study in 1990 to 1994, who had diet, body size, and lifestyle reassessed in 2003 to 2007 (“baseline”), were followed-up through June 2021. We constructed diet and standardized lifestyle scores based on core WCRF/AICR recommendations on diet, alcohol intake, body size and physical activity, and additional scores incorporating weight change, sedentary behavior, and smoking. Associations with cancer risk were estimated using Cox regression, adjusting for confounders.
Results
During follow-up (mean = 16 years), 4,710 incident cancers were diagnosed. For highest quintile (“most adherent”) of the standardized lifestyle score, compared with lowest (“least adherent”), a HR of 0.82 [95% confidence interval (CI): 0.74–0.92] was observed for total cancer. This association was stronger with smoking included in the score (HR = 0.74; 95% CI: 0.67–0.81). A higher score was associated with lower breast and prostate cancer risk for the standardized score, and with lung, stomach, rectal, and pancreatic cancer risk when the score included smoking. Our analyses identified alcohol use, waist circumference and smoking as key drivers of associations with total cancer risk.
Conclusions
Adherence to WCRF/AICR cancer prevention recommendations is associated with lower cancer risk.
Impact
With <0.2% of our sample fully adherent to the recommendations, the study emphasizes the vast potential for preventing cancer through modulation of lifestyle habits.
Esophageal cancer is a highly lethal disease. Despite an increasing incidence of adenocarcinoma in last decades, squamous cell carcinoma remains the predominant cell type worldwide. The majority of squamous cell cancers are from the East. Risk factors for the development of esophageal squamous cell carcinoma differ between high- and low-incidence regions. Tobacco and alcohol intake are the two major risks factors for esophageal squamous cell carcinoma. They also have a synergistic effect; the mechanism of which is now better understood. Other dietary factors include lack of certain micronutrients, consumption of food with carcinogenic ingredients, eating habits and food preservation methods. Genetic factors, viral infection and other premalignant conditions also play a role. Studying epidemiology and pathogenesis of the disease allows policymakers to enact public health policies to prevent the disease through health education and risk factors avoidance. Screening for early disease detection in high-risk populations could improve overall outcome.
Cancers of the upper digestive tract, including oral cavity, pharynx, larynx, esophagus squamous cell carcinoma), liver, colorectum, and female breast were causally related to alcohol consumption. This chapter introduces to the book part on cancer and alcohol consumption. According to a recent report from the International Agency for Research on Cancer (IARC), 4.1% of all new cases of cancer, are attributable to alcohol consumption. They could have been avoided if there had been no alcohol use. Mechanisms of cancer development during alcohol exposure are also briefly discussed. Of note, not ethanol itself but its mandatory oxidation to acetaldehyde causes carcinogenesis, in association with multiple other pathways that lead to the generation of reactive oxygen species (ROS) and accumulation of iron. Together, these metabolites are genotoxic, impair DNA repair, cause cell injury, enhanced cell regeneration and, hence, provide conditions for genomic instability, an optimal environment for cancer formation. In addition, a combination of immunosuppression and reduced tumor clearance through elimination pathways such as apoptosis further contribute to carcinogenesis. At the systemic level, enhanced red blood cell (RBC) turnover in combination with liver and bone marrow injury provide an additional novel loop that specifically challenges the immune system and provides enhanced toxic iron trafficking.
Alcohol consumption (AC) and metabolic syndrome (MS) represent the first cause of liver disease, hepatocellular carcinoma and liver transplantation. The habit of consuming alcoholic beverages and the presence of MS and non-alcoholic fatty liver disease (NAFLD) often coexist in the same patient. The histoclinical boundaries between alcohol related liver disease (ALD) and NAFLD are often not well defined. The co-presence of AC and MS increases the risk of hepatic and extra-hepatic disease. The terminological evolution from NAFLD to metabolic associated fatty liver disease (MAFLD) is certainly a useful advance. However, it is known that the appearance of liver fibrosis increases oncologic and cardiovascular disease risk, which in the case of cirrhosis can be present even in the absence of steatosis and that the mechanisms of fibrogenesis can act independently of the presence of steatosis/steatohepatitis. For this reason, as already stated recently, a further terminological evolution can be hypothesized. This article was originally published with mistakes in the text. The new corrected citable version appears below.
Gastric cancer is the fourth leading cause of morbidity worldwide and is known to affect various gastric organs, including the esophagus, intestine, colon, and pancreas. There are variable factors responsible for the development of gastric tumors, such as environmental factors, EPV, hepatitis B and C, and other genetic factors. Phytoactives, or secondary metabolites of plants, have a wide range of biological impacts, including the capacity to prevent cancer in humans. They have this anti-cancerous impact because of their multi-target mechanism of action, which also includes antioxidant, anti-proliferative, cell apoptosis, and anti-mutagenic effects. To epitomize the role of vital dietary phytoactives as a new approach for treating gastric cancer and explains various mechanisms for their anti-cancerous activity. H. pylori-associated gastric tumors are the most common, and Phytoactives such as curcumin, piperine, walnut oil, tea, and others possess anticancer properties. They have shown anticancer activity against gastric tumor cell lines via different mechanisms like cell cycle arrest, apoptosis, inhibition of cell proliferation, adhesion, colonization of cancer cells, inhibition of inflammatory mediators, tumor cell bioenergetics, up and down-regulation of various gene and protein expression, and chelation and scavenging of ROS.
Background:
The rate of metachronous recurrence after endoscopic submucosal dissection for early-stage esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma is as high (10-15%). The acetaldehyde breath test may detect acetaldehyde dehydrogenase 2 gene polymorphisms. Therefore, we evaluated its usefulness in assessing metachronous recurrence in patients with esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma.
Methods:
A total of 76 patients underwent endoscopic submucosal dissection for esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma and were followed up for at least 3 years (non-recurrence group: 52 patients; recurrence group: 24 patients). The risk factors for carcinogenesis were compared between the recurrence and non-recurrence groups, and the acetaldehyde-to-ethanol ratio was assessed. The cutoff acetaldehyde-to-ethanol ratio that correlated with recurrence was established, and the cumulative recurrence rate was evaluated.
Results:
The recurrence group had a higher acetaldehyde-to-ethanol ratio, daily alcohol consumption, and Lugol-voiding lesion grade than the non-recurrence group in the univariate analysis. The cutoff acetaldehyde-to-ethanol ratio for recurrence was 28.1 based on the receiver operating characteristic curve. The multivariate analysis revealed an acetaldehyde-to-ethanol ratio of > 28.1 and a Lugol-voiding lesion grade associated with carcinogenesis. Patients with an acetaldehyde-to-ethanol ratio of ≥ 28.1 had a significantly high recurrence rate using the Kaplan-Meier method.
Conclusions:
The acetaldehyde-to-ethanol ratio detected using the acetaldehyde breath test could be a novel biomarker of metachronous recurrence after endoscopic submucosal dissection in patients with esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma.
Trial registration number:
UMIN000040615.
Background
HPV-positive head and neck squamous cell carcinoma (HNSCC) differs from HPV-negative HNSCC in clinical features, biological behavior, pathological manifestations, cytogenetics and tend to have better outcome. Immunohistochemical (IHC) p16 staining is highly sensitive for HPV status exam, but has a certain probability of false positives, and the accurate result of p16 expression could be challenging due to the limitation of the biopsy location and quantity. As a non-invasive approach, dual-layer detector spectral CT (DLSCT) provides multi-parameter quantitative analysis, which could help better reflect the changes of tumor characteristics. Hence, this study aimed to evaluate the spectral-derived differences between the p16( +) and p16(–) group of HNSCC so as to explore the application in preoperative diagnosis in differentiating the p16 expression status of HNSCC.
Materials and methods
The spectral data of 35 patients with biopsy confirmed HNSCC were retrospectively analyzed and compared between p16( +) (n = 11) and p16(−) (n = 25) group. All statistical analyses were performed on SPSS v26.0.
Results
Effective atomic number (Zeff), slope value of virtual monoenergetic image (VMI), and normalized iodine density (NID) of p16( +) group were all significantly lower than p16(−) group (8.36 (8.24, 8.42) vs. 8.57 (8.38, 8.85), 2.45 (2.22, 2.64) vs. 3.06 (2.50, 3.82), 0.43 ± 0.09 vs. 0.55 ± 0.14, respectively) (p < 0.05). Besides, NID showed a good ability to discriminate p16(−) HNSCC from p16( +) HNSCC (AUC = 0.788) with a threshold value of 0.495.
Conclusion
DLSCT could be helpful for the differentiation of p16 expression in HNSCC.
Background:
The impacts of socioeconomic status (SES) on COVID-19-related changes in cancer prevention behavior have not been thoroughly investigated. We conducted a cohort study to examine the effects of SES on changes in cancer prevention behaviors during the COVID-19 pandemic.
Methods:
We invited adult participants from previous studies conducted at Ohio State University to participate in a study assessing the impact of COVID-19 on various behaviors. Post-COVID-19 cancer prevention behaviors, including physical activity, daily intake of fruits and vegetables, alcohol and tobacco consumption, and qualitative changes in post-COVID-19 behaviors relative to pre-COVID levels, were used to construct a prevention behavior change index that captures the adherence status and COVID-related changes in each behavior, with higher index scores indicating desirable changes in prevention behaviors. Participants were classified into low, middle, or high SES based on household income, education, and employment status. Adjusted regression models were used to examine the effects of SES on changes in cancer prevention behaviors during the COVID-19 pandemic.
Results:
The study included 6,136 eligible participants. The average age was 57 years, 67% were women, 89% were non-Hispanic Whites, and 33% lived in non-metro counties. Relative to participants with high SES, those with low SES had a 24% [adjusted relative ratio, aRR = 0.76 (95%CI 0.72-0.80)], 11% [aRR = 0.89 (95%CI 0.86-0.92)], and 5% [aRR = 0.95 (95%CI 0.93-0.96)], lower desirable changes in prevention behaviors for physical activity, fruit and vegetable intake, and tobacco use, respectively. Low SES had a higher desirable change in alcohol consumption prevention behaviors, 16% [aRR = 1.16 (95%CI 1.13-1.19)] relative to high SES. The adjusted odds of an overall poor change in prevention behavior were adjusted odds ratio (aOR) 1.55 (95%CI 1.27 to 1.89) and aOR 1.40 (95%CI 1.19 to 1.66), respectively, higher for those with low and middle SES relative to those with high SES.
Conclusion:
The adverse impacts of COVID-19 on cancer prevention behaviors were seen most in those with lower SES. Public health efforts are currently needed to promote cancer prevention behaviors, especially amongst lower SES adults.
Aldehydes are widespread in the environment, with multiple sources such as food and beverages, industrial effluents, cigarette smoke, and additives. The toxic effects of exposure to several aldehydes have been observed in numerous studies. At the molecular level, aldehydes damage DNA, cross-link DNA and proteins, lead to lipid peroxidation, and are associated with increased disease risk including cancer. People genetically predisposed to aldehyde sensitivity exhibit severe health outcomes. In various diseases such as Fanconi's anemia and Cockayne syndrome, loss of aldehyde-metabolizing pathways in conjunction with defects in DNA repair leads to widespread DNA damage. Importantly, aldehyde-associated mutagenicity is being explored in a growing number of studies, which could offer key insights into how they potentially contribute to tumorigenesis. Here, we review the genotoxic effects of various aldehydes, focusing particularly on the DNA adducts underlying the mutagenicity of environmentally derived aldehydes. We summarize the chemical structures of the aldehydes and their predominant DNA adducts, discuss various methodologies, in vitro and in vivo, commonly used in measuring aldehyde-associated mutagenesis, and highlight some recent studies looking at aldehyde-associated mutation signatures and spectra. We conclude the Review with a discussion on the challenges and future perspectives of investigating aldehyde-associated mutagenesis.
Obesity is associated with several types of cancer and fat distribution, which differs dramatically between sexes, has been suggested to be an independent risk factor. However, sex-specific effects on cancer risk have rarely been studied. Here we estimate the effects of fat accumulation and distribution on cancer risk in females and males. We performed a prospective study in 442,519 UK Biobank participants, for 19 cancer types and additional histological subtypes, with a mean follow-up time of 13.4 years. Cox proportional hazard models were used to estimate the effect of 14 different adiposity phenotypes on cancer rates, and a 5% false discovery rate was considered statistically significant. Adiposity-related traits are associated with all but three cancer types, and fat accumulation is associated with a larger number of cancers compared to fat distribution. In addition, fat accumulation or distribution exhibit differential effects between sexes on colorectal, esophageal, and liver cancer.
Chronic alcohol drinking rewires circulating monocytes and tissue-resident macrophages towards heightened inflammatory states with compromised anti-microbial defenses. As these effects remain consistent in short-lived monocytes after a 1-month abstinence period it is unclear whether these changes are restricted to the periphery or mediated through alterations in the progenitor niche. To test this hypothesis, we profiled monocytes/macrophages and hematopoietic stem cell progenitors (HSCP) of the bone marrow compartment from rhesus macaques after 12 months of ethanol consumption using a combination of functional assays and single cell genomics. Bone marrow-resident monocytes/macrophages from ethanol-consuming animals exhibited heightened inflammation. Differentiation of HSCP in vitro revealed skewing towards monocytes expressing neutrophil-like markers with heightened inflammatory responses to bacterial agonists. Single cell transcriptional analysis of HSCPs showed reduced proliferation but increased inflammatory markers in mature myeloid progenitors. We observed transcriptional signatures associated with increased oxidative and cellular stress as well as oxidative phosphorylation in immature and mature myeloid progenitors. Single cell analysis of the chromatin landscape showed altered drivers of differentiation in monocytes and progenitors. Collectively, these data indicate that chronic ethanol drinking results in remodeling of the transcriptional and epigenetic landscapes of the bone marrow compartment leading to altered functions in the periphery.
The tongue and floor of the mouth are high-risk sites for oral squamous cell carcinoma (OSCC), while smoking is its most significant risk factor. Recently, questions have been raised as to the role of the oral microbiome in OSCC because of a wealth of evidence demonstrating that the microbiome of OSCC differs from that of healthy mucosa. However, oral site and smoking also have a significant impact on oral microbial communities, and to date, the role these factors play in influencing the dysbiotic microbial communities of OSCC and precursor lesions has not been considered. This review aims to examine the influence of site and smoking on the oral microbiome and, in turn, whether these microbiome changes could be involved in oral carcinogenesis.
Alcohol consumption is known to increase risk for chronic diseases and other negative health outcomes. Abstinence, even temporary, from alcohol consumption can have positive health impacts. In this article, we describe implementation and process evaluation of Ochsner Eat Fit’s Alcohol Free for 40 (AFF40), an annual, 40-day voluntary alcohol abstinence challenge that takes place in six regions of Louisiana. Participants are challenged to abstain from alcohol consumption for 40 days to promote behavior change. To support participants’ success, staff conduct pre and post metrics (physical and laboratory) and host community-based events to encourage replacement behaviors. Process evaluation included measures of reach, recruitment, dose, and fidelity through tracking of participant registrations, an exit survey, media analytics, and program activity logs. In 2021, 493 participants enrolled in AFF40, with 347 completing laboratory metrics and 298 completing physical metrics. Majority of exit survey respondents (74.5%) reported no alcohol consumption during the 40-day challenge and that they planned to participate in AFF40 2022 (90.9%). The Eat Fit team documented moderate engagement (48.7% of enrolled participants) in program events. Social and digital impressions and page views recorded 23,591 hits while print media resulted in over 750,000 impressions. AFF40 has shown to be highly engaging for participants and effective in supporting temporary abstinence from alcohol. Incorporating stronger methods and evaluation will enhance future program implementation and community impact. Lessons learned and implications for practice are transferable to other community-based efforts to reduce alcohol consumption.
Brain tumorBrain tumor (BT) is the second most common pediatric cancer, one of the most common cancers among adults, and the major cause of cancer-related morbidityMorbidityand mortalityMortality worldwide. Both genetics and environment can contribute to BT induction. One of the environmental risks is dietDiet which has not been proven as a certain hazard yet. The objective of the current chapter was to review the literature concerning both positive and negative effects of nutritionNutrition on BT risk.
Purpose
Non-communicable diseases generate the largest number of avoidable deaths often caused by risk factors such as alcohol, smoking, and unhealthy diets. Our study investigates the association between amount and context of alcohol consumption and mortality from major non-communicable diseases in Switzerland.
Methods
Generalized linear regression models were fitted on data of the cross-sectional population-based National Nutrition Survey menuCH (2014–2015, n = 2057). Mortality rates based on the Swiss mortality data (2015–2018) were modeled by the alcohol consumption group considering the amount and context (i.e., during or outside mealtime) of alcohol consumption and potential confounders. The models were checked for spatial autocorrelation using Moran’s I statistic. Integrated nested Laplace approximation (INLA) models were fitted when evidence for missing spatial information was found.
Results
Higher mortality rates were detected among drinkers compared to non-drinkers for all-cancer (rate ratio (RR) ranging from 1.01 to 1.07) and upper aero-digestive tract cancer (RR ranging from 1.15 to 1.20) mortality. Global Moran’s I statistic revealed spatial autocorrelation at the Swiss district level for all-cancer mortality. An INLA model led to the identification of three districts with a significant decrease and four districts with a significant increase in all-cancer mortality.
Conclusion
Significant associations of alcohol consumption with all-cancer and upper aero-digestive tract cancer mortality were detected. Our study results indicate the need for further studies to improve the next alcohol-prevention scheme and to lower the number of avoidable deaths in Switzerland.
Common liver tissue damage is mainly due to the accumulation of toxic aldehydes in lipid peroxidation under oxidative stress. Cumulative toxic aldehydes in the liver can be effectively metabolized by acetaldehyde dehydrogenase 2 (ALDH2), thereby alleviating various liver diseases. Notably, gene mutation of ALDH2 leads to impaired ALDH2 enzyme activity, thus aggravating the progress of liver diseases. However, the relationship and specific mechanism between ALDH2 and liver diseases are not clear. Consequently, the review explains the relationship between ALDH2 and liver diseases such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), liver fibrosis and hepatocellular carcinoma (HCC). In addition, this review also discusses ALDH2 as a potential therapeutic target for various liver diseases,and focuses on summarizing the regulatory mechanism of ALDH2 in these liver diseases.
In Taiwan, the age-standardized incidence of EC, especially esophageal squamous cell carcinoma (ESCC), has increased substantially during the past thirty years. We described the incidence trends of EC from 1985–2019 by an average annual percentage change (AAPC) and age-period-cohort model by using Taiwan Cancer Registry data. Age-period-cohort modeling was used to estimate the period and cohort effects of ESCC and esophageal adenocarcinoma (EAC). The Spearman’s correlation coefficient was used to analyze the correlation between age-adjusted incidence rates of EC and the prevalence of risk factors from national surveys. The results showed the incidence rate of ESCC in men (AAPC = 4.2, 95% CI = 3.1–5.4, p < 0.001) increased prominently from 1985–1989 to 2015–2019 while that of EAC in men (AAPC = 1.2, 95% CI = 0.9–1.5, p < 0.001) and ESCC in women (AAPC = 1.7, 95% CI = 1.4–2.1, p < 0.001) increased to a lesser degree. Increased period effects were observed in ESCC in men, ESCC in women, and EAC in men. High correlations were found between the risk factors and the increased birth-cohort effects of ESCC (p < 0.05). To conclude, the incidence of ESCC in both sex and EAC in men increased with statistical significance in recent decades. The increased prevalence of risk factors from approximately 1970–1995 could explain the increased cohort effects of ESCC.
Alcohol readily diffuses through cell membranes and is toxic in a dose-response relationship to numerous body parts of the body, including the digestive tract, liver, cardiovascular system, brain, reproductive system, excretory system and respiratory system, as well as adversely impacting fetal development. Alcohol also acts synergistically with numerous other toxins, including benzene, xylene, carbon tetrachloride, DEET insect repellant, cocaine and others. Alcohol enhances oxidative stress, resulting in mitochondrial damage, damaging cell membranes and impacting the immune system, leading to cytokine production and other mechanistic pathways. Alcohol elevates oxidative stress via the stimulation of cytochrome P450 enzymes and reduction of antioxidant levels. It is the primary cause of liver cirrhosis and is associated with the onset of other diseases.
Background
Alcohol use disorder (AUD) is a significant public health concern worldwide. Alcohol consumption is a leading cause of death in the United States and has a significant negative impact on individuals and society. Relapse following treatment is common, and adjunct intervention approaches to improve alcohol outcomes during early recovery continue to be critical. Interventions focused on increasing physical activity (PA) may improve AUD treatment outcomes. Given the ubiquity of smartphones and activity trackers, integrating this technology into a mobile app may be a feasible, acceptable, and scalable approach for increasing PA in individuals with AUD.
Objective
This study aims to test the Fit&Sober app developed for patients with AUD. The goals of the app were to facilitate self-monitoring of PA engagement and daily mood and alcohol cravings, increase awareness of immediate benefits of PA on mood and cravings, encourage setting and adjusting PA goals, provide resources and increase knowledge for increasing PA, and serve as a resource for alcohol relapse prevention strategies.
Methods
To preliminarily test the Fit&Sober app, we conducted an open pilot trial of patients with AUD in early recovery (N=22; 13/22, 59% women; mean age 43.6, SD 11.6 years). At the time of hospital admission, participants drank 72% of the days in the last 3 months, averaging 9 drinks per drinking day. The extent to which the Fit&Sober app was feasible and acceptable among patients with AUD during early recovery was examined. Changes in alcohol consumption, PA, anxiety, depression, alcohol craving, and quality of life were also examined after 12 weeks of app use.
Results
Participants reported high levels of satisfaction with the Fit&Sober app. App metadata suggested that participants were still using the app approximately 2.5 days per week by the end of the intervention. Pre-post analyses revealed small-to-moderate effects on increase in PA, from a mean of 5784 (SD 2511) steps per day at baseline to 7236 (SD 3130) steps per day at 12 weeks (Cohen d=0.35). Moderate-to-large effects were observed for increases in percentage of abstinent days (Cohen d=2.17) and quality of life (Cohen d=0.58) as well as decreases in anxiety (Cohen d=−0.71) and depression symptoms (Cohen d=−0.58).
Conclusions
The Fit&Sober app is an acceptable and feasible approach for increasing PA in patients with AUD during early recovery. A future randomized controlled trial is necessary to determine the efficacy of the Fit&Sober app for long-term maintenance of PA, ancillary mental health, and alcohol outcomes. If the efficacy of the Fit&Sober app could be established, patients with AUD would have a valuable adjunct to traditional alcohol treatment that can be delivered in any setting and at any time, thereby improving the overall health and well-being of this population.
Trial Registration
ClinicalTrials.gov NCT02958280; https://www.clinicaltrials.gov/ct2/show/NCT02958280
To evaluate the strength of the evidence provided by the epidemiological literature on the association between alcohol consumption and the risk of 18 neoplasms, we performed a search of the epidemiological literature from 1966 to 2000 using several bibliographic databases. Meta-regression models were fitted considering linear and non-linear effects of alcohol intake. The effects of characteristics of the studies, of selected covariates (tobacco) and of the gender of individuals included in the studies, were also investigated as putative sources of heterogeneity of the estimates. A total of 235 studies including over 117 000 cases were considered. Strong trends in risk were observed for cancers of the oral cavity and pharynx, oesophagus and larynx. Less strong direct relations were observed for cancers of the stomach, colon and rectum, liver, breast and ovary. For all these diseases, significant increased risks were found also for ethanol intake of 25 g per day. No significant nor consistent relation was observed for cancers of the pancreas, lung, prostate or bladder. Allowance for tobacco appreciably modified the relations with laryngeal, lung and bladder cancers, but not those with oral, oesophageal or colorectal cancers. This meta-analysis showed no evidence of a threshold effect for most alcohol-related neoplasms. The inference is limited by absence of distinction between lifelong abstainers and former drinkers in several studies, and the possible selective inclusion of relevant sites only in cohort studies.
Epidemiologic studies have generally reported positive associations between alcohol consumption and risk for colorectal cancer. However, findings related to specific alcoholic beverages or different anatomic sites in the large bowel have been inconsistent.
To examine the relationship of total alcohol intake and intake from specific beverages to the incidence of colorectal cancer and to evaluate whether other potential risk factors modify the association.
Pooled analysis of primary data from 8 cohort studies in 5 countries.
North America and Europe.
489,979 women and men with no history of cancer other than nonmelanoma skin cancer at baseline.
Alcohol intake was assessed in each study at baseline by using a validated food-frequency questionnaire.
During a maximum of 6 to 16 years of follow-up across the studies, 4687 cases of colorectal cancer were documented. In categorical analyses, increased risk for colorectal cancer was limited to persons with an alcohol intake of 30 g/d or greater (approximately > or =2 drinks/d), a consumption level reported by 4% of women and 13% of men. Compared with nondrinkers, the pooled multivariate relative risks were 1.16 (95% CI, 0.99 to 1.36) for persons who consumed 30 to less than 45 g/d and 1.41 (CI, 1.16 to 1.72) for those who consumed 45 g/d or greater. No significant heterogeneity by study or sex was observed. The association was evident for cancer of the proximal colon, distal colon, and rectum. No clear difference in relative risks was found among specific alcoholic beverages.
The study included only one measure of alcohol consumption at baseline and could not investigate lifetime alcohol consumption, alcohol consumption at younger ages, or changes in alcohol consumption during follow-up. It also could not examine drinking patterns or duration of alcohol use.
A single determination of alcohol intake correlated with a modest relative elevation in colorectal cancer rate, mainly at the highest levels of alcohol intake.
The authors examined the role of diet in the high-risk population of Central Europe among 1,065 incident kidney cancer cases and 1,509 controls in Russia, Romania, Poland, and the Czech Republic. They observed an increased association with kidney cancer for consumption of milk (odds ratio (OR) = 1.46, 95% confidence interval (CI): 1.15, 1.84) and yogurt (OR = 1.34, 95% CI: 1.07, 1.67), as well as all meat (OR = 1.27, 95% CI: 1.06, 1.51 compared with the lowest tertile). High consumption of all vegetables (OR = 0.64, 95% CI: 0.51, 0.80) and cruciferous vegetables (OR = 0.68, 95% CI: 0.55, 0.84) was inversely associated with kidney cancer. In addition, high consumption of preserved vegetables increased the risk of kidney cancer (OR = 1.66, 95% CI: 1.24, 2.21). Alcohol consumption did not appear to be associated with kidney cancer. This 1999-2003 study provides further evidence that diet may play a role in the development of kidney cancer, with a particularly strong protective association for high vegetable intake. The increased risk associated with dairy products, preserved vegetables, and red meat provides clues to the high rates of kidney cancer in this population.
The distribution of the human liver alcohol dehydrogenase, ADH2, and aldehyde dehydrogenase, ALDH2, genotypes in 21 different populations comprising Mongoloids, Caucasoids, and Negroids was determined by hybridization of the amplified genomic DNA with allele-specific oligonucleotide probes. Whereas the frequency of the ADH
1
2
allele was found to be relatively high in the Caucasoids, Mexican Mestizos, Brazilian Indios, Swedish Lapps, Papua New Guineans and Negroids, the frequency of the ADH
2
2
gene was considerably higher in the Mongoloids and Australian Aborigines. The atypical ALDH2 gene (ALDH22) was found to be extremely rare in Caucasoids, Negroids, Papua New Guineans, Australian Aborigines and Aurocanians (South Chile). In contrast, this mutant gene was found to be widely prevalent among the Mongoloids. Individuals possessing the abnormal ALDH2 gene show alcohol-related sensitivity responses (e.g. facial flushing), have the tendency not to be habitual drinkers, and apparently suffer less from alcoholism and alcohol-related liver disease.
Although epidemiological studies indicate that ethanol consumption and the risk of breast cancer are positively associated in women, experimental animal models have not yet been developed that provide evidence to support this relationship. To clarify alcohol-related liver injury, it is important to reproduce, in laboratory small animals, the liver fibrosis observed in human alcoholics. However, in mice the induction of fibrosis has failed. The present study describes the first experimental models to produce mammary tumors in female ICR mice and liver fibrosis in male ICR mice treated long-term with ethanol.
The study consisted of two parts. To induce mammary tumors, female ICR mice were given 10% to 15% ethanol solution as the sole drinking fluid for 25 months, with solid diet supplied ad libitum. To induce liver fibrosis, male ICR mice were given 10% to 15% ethanol solution as the sole drinking fluid for 10 to 15 months. Control female and male mice were given tap water.
In 9 (45%) of 20 ethanol-treated female mice, mammary tumors occurred at 8 to 24 months after ethanol intake began, whereas spontaneous mammary tumor was not found in the 20 control female mice. The tumors were composed histopathologically of either papillary adenocarcinoma or medullary adenocarcinoma of glandular epithelial origin. In the ethanol-treated male mice, early hepatic fibrosis at the centrilobular and pericellular areas and central-central bridging were observed at the 10th month, and marked fibrosis at the centrilobular, pericellular, and periportal areas and bridging between the neighboring vascular tissues were observed at the 15th month, which suggested that the initial fibrosis arose from the centrilobular area. No abnormalities other than mild fatty infiltration were found in livers of the control male mice.
These murine models may be useful to study the role of ethanol in mammary tumorigenesis and the pathogenetic mechanisms of ethanol liver injury.
Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.
Methyl alcohol was administered in drinking water supplied ad libitum at doses of 20,000, 5,000, 500, or 0 ppm to groups of male and female Sprague-Dawley rats 8 weeks old at the start of the experiment. Animals were kept under observation until spontaneous death. Ethyl alcohol was administered by ingestion in drinking water at a concentration of 10% or 0% supplied ad libitum to groups of male and female Sprague-Dawley rats; breeders and offspring were included in the experiment. Treatment started at 39 weeks of age (breeders), 7 days before mating, or from embryo life (offspring) and lasted until their spontaneous death. Under tested experimental conditions, methyl alcohol and ethyl alcohol were demonstrated to be carcinogenic for various organs and tissues. They must also be considered multipotential carcinogenic agents. In addition to causing other tumors, ethyl alcohol induced malignant tumors of the oral cavity, tongue, and lips. These sites have been shown to be target organs in man by epidemiologic studies.
To provide information on the effects of alcohol and tobacco on laryngeal cancer and its subsites.
This was a case-control study conducted between 1992 and 2000 in northern Italy and Switzerland. A total of 527 cases of incident squamous-cell carcinoma of the larynx and 1297 hospital controls frequency-matched with cases on age, sex, and area of residence were included. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression.
In comparison with never smokers, ORs were 19.8 for current smokers and 7.0 for ex-smokers. The risk increased in relation to the number of cigarettes (OR = 42.9 for > or = 25 cigarettes/day) and for duration of smoking (OR = 37.2 for > or = 40 years). For alcohol, the risk increased in relation to number of drinks (OR = 5.9 for > or = 56 drinks per week). Combined alcohol and tobacco consumption showed a multiplicative (OR = 177) rather than an additive risk. For current smokers and current drinkers the risk was higher for supraglottis (ORs 54.9 and 2.6, respectively) than for glottis (ORs 7.4 and 1.8) and others subsites (ORs 10.9 and 1.9).
Our study shows that both cigarette smoking and alcohol drinking are independent risk factors for laryngeal cancer. Heavy consumption of alcohol and cigarettes determined a multiplicative risk increase, possibly suggesting biological synergy.
Oral, pharyngeal and esophageal cancers are 3 of the 5 most common cancer sites in Indian men. To assess the effect of different patterns of smoking, chewing and alcohol drinking in the development of the above 3 neoplasms and to determine the interaction among these habits, we conducted a case-control study in Chennai and Trivandrum, South India. The cases included 1,563 oral, 636 pharyngeal and 566 esophageal male cancer patients who were compared with 1,711 male disease controls from the 2 centers as well as 1,927 male healthy hospital visitors from Chennai. We observed a significant dose-response relationship for duration and amount of consumption of the 3 habits with the development of the 3 neoplasms. Tobacco chewing emerged as the strongest risk factor for oral cancer, with the highest odds ratio (OR) for chewing products containing tobacco of 5.05 [95% confidence internal (CI) 4.26-5.97]. The strongest risk factor for pharyngeal and esophageal cancers was tobacco smoking, with ORs of 4.00 (95% CI 3.07-5.22) and 2.83 (95% CI 2.18-3.66) in current smokers, respectively. An independent increase in risk was observed for each habit in the absence of the other 2. For example, the OR of oral cancers for alcohol drinking in never smokers and never chewers was 2.56 (95% CI 1.42-4.64) and that of esophageal cancers was 3.41 (95% CI 1.46-7.99). Furthermore, significant decreases in risks for all 3 cancer sites were observed in subjects who quit smoking even among those who had quit smoking 2-4 years before the interview.
To assess the role of diet and vitamin or mineral supplements in renal cell carcinoma (RCC) risk.
Mailed questionnaires were completed by 1279 (691 male and 588 female) newly diagnosed histologically confirmed RCC cases and 5370 (2696 male and 2674 female) population controls between 1994 and 1997 in eight Canadian provinces. Measurement included information on socioeconomic status, smoking habits, alcohol use, diet, and vitamin or mineral supplements. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived through unconditional logistic regression.
A significant inverse association with RCC was observed with increasing total consumption of vegetables and vegetable juices for males and females combined. Increased consumption for two specific vegetable groups was inversely associated among females but not males: for females, the adjusted ORs for the highest quartile of consumption compared with the lowest were 0.5 (95% CI = 0.4-0.7) and 0.6 (95% CI = 0.4-0.8), p < 0.0001 and p = 0.0002 for dark-green vegetables and cruciferous vegetables, respectively. An increased risk was observed (for males and females combined) with increased consumption of hamburger and sausage: adjusted ORs for highest level versus lowest level were 1.4 (95% CI = 1.1-1.8) and 1.5 (95% CI = 1.2-2.0), respectively, p = 0.003 and 0.01. Beef, pork or lamb as a main dish and processed meats were also associated with increased RCC. Red meats and processed meats had a positive association with RCC among males who had smoked or were overweight; among females this was the case for hamburger only. Significant inverse associations were observed for females taking vitamin E or calcium supplements. Among males, those taking vitamin E or iron for more than 5 years had reduced risks.
Our findings add to the evidence that diet may play an important role in the etiology of RCC; the risk of RCC may be reduced by changes in nutritional habits.
Previous epidemiological studies of the relation between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) have been inconsistent, probably because of small sample sizes of individual studies that result from stratification by NHL subtype and type of alcoholic beverage. We aimed to assess the role of alcohol consumption in NHL with sufficient sample size to analyse by both type of alcoholic beverage and disease subtype.
We obtained original data from nine case-control studies from the USA, UK, Sweden, and Italy in the International Lymphoma Epidemiology Consortium (InterLymph), yielding a pooled study population of 15 175 individuals (6492 cases and 8683 controls). We derived odds ratios (OR) and 95% CI from unconditional logistic regression models, controlling for study centre and other confounding factors. Heterogeneity between studies was assessed by comparison of results from joint fixed-effects logistic regression and two-stage random-effects logistic regression, and by calculation of Wald chi(2) statistics.
People who drank alcohol had a lower risk of NHL than did non-drinkers (OR 0.83 [95% CI 0.76-0.89]). Compared with non-drinkers, risk estimates were lower for current drinkers than for former drinkers (0.73 [0.64-0.84] vs 0.95 [0.80-1.14]), but risk did not decrease with increasing alcohol consumption. The protective effect of alcohol did not vary by beverage type, but did change with NHL subtype. The lowest risk estimates were recorded for Burkitt's lymphoma (0.51 [0.33-0.77]).
People who drink alcoholic beverages might have a lower risk of NHL than those who do not, and this risk might vary by NHL subtype. Further study designs are needed to determine whether confounding lifestyle factors or immunomodulatory effects of alcohol explain this association.
Alcoholic beverages are causally related to cancer of the oral cavity, pharynx, larynx and esophagus. Ethanol is oxidized to acetaldehyde and then to acetate by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), both of which have genetic polymorphisms. A review of case-control studies of the effects of ALDH2, ADH2 and ADH3 genotypes shows consistently positive associations between inactive heterozygous ALDH2 and the less-active ADH2 genotypes and the risk for esophageal cancer in East Asian heavy drinkers and this enzyme-related vulnerability may extend to light-to-moderate drinkers. Some studies suggest similar associations with the risk for head and neck cancer in moderate-to-heavy-drinking Japanese. An established carcinogen in experimental animals, acetaldehyde can interact with human DNA. ALDH2-associated cancer susceptibility fits into a scenario in which acetaldehyde plays a critical role in the development of human cancer. Alcohol flushing and drinking behavior may partly explain this carcinogenic effect in carriers of less-active ADH2 genotypes. Whether the ADH3 genotype influences head and neck cancer risk in Western nations is controversial. Professional and public education about risky conditions connected to the ALDH2 and ADH2 genotypes and environmental factors is important in a new strategic approach to the prevention of alcohol-related cancers in East Asians. The use of simple tests to identify inactive ALDH2 on the basis of alcohol flushing responses could benefit many people, by helping them to identify their own cancer risks. Such testing could also help clinicians diagnose esophageal cancer earlier, through the use of endoscopic screening in the high-risk population.
Mendelian randomization, the use of common polymorphisms as surrogates for measuring exposure levels in epidemiologic studies, provides one method of assessing the causal nature of some environmental exposures. This can be illustrated by looking at the association between the ALDH2 polymorphism and esophageal cancer. Alcohol drinking is considered a risk factor for esophageal cancer, and exposure to high levels of acetaldehyde, the principal metabolite of alcohol, may be responsible for the increased cancer risk. The ability to metabolize acetaldehyde is encoded by the ALDH2 gene, which is polymorphic in some populations. The ALDH2*2 allele produces an inactive protein subunit, which is unable to metabolize acetaldehyde. An individual's genotype at this locus may influence their esophageal cancer risk through two mechanisms, first through influencing alcohol intake and second through influencing acetaldehyde levels. We have carried out a meta-analysis of studies looking at the ALDH2 genotype and esophageal cancer and found that risk was reduced among *2*2 homozygotes [odds ratio (OR), 0.36; 95% confidence interval (95% CI), 0.16-0.80] and increased among heterozygotes (OR, 3.19; 95% CI, 1.86-5.47) relative to *1*1 homozygotes. This provides strong evidence that alcohol intake increases the risk of esophageal cancer and individuals whose genotype results in markedly lower intake, because they have an adverse reaction to alcohol are thus protected. This meta-analysis also provides evidence that acetaldehyde plays a carcinogenic role in esophageal cancer. The two different processes operating as a result of the ALDH2 genotype have implications for the interpretation of studies using the Mendelian randomization paradigm.
To study the role of tobacco smoking and alcohol drinking in the etiology of non-Hodgkin's lymphoma (NHL), we conducted a multicenter case-control study in Spain, France, Germany, Italy, Ireland and Czech Republic between 1998 and 2004, which included 1,742 cases of NHL and 2,465 controls matched on age, sex and recruitment area. Tobacco smoking was not associated with the risk of NHL overall or with risk of specific histological subtypes. Similarly, there was no association between alcohol drinking and the risk of NHL overall or across histological subtypes. However, a protective effect of alcohol drinking was observed among men (OR = 0.76, 95% CI = 0.62-0.93) and in non-Mediterranean countries (OR = 0.73, 95% CI = 0.61-0.86). There was no evidence of interaction between alcohol drinking and tobacco smoking in NHL etiology. The results of this large-scale European study did not support an association between tobacco and NHL and suggested a protective effect of alcohol on development of NHL for men and in non-Mediterranean countries.
Drinking alcohol is a risk factor for cancers of the oral cavity, pharynx, larynx, and esophagus. Although many studies suggest that acetaldehyde, a major metabolite of orally ingested alcohol, plays a crucial role in cancer initiation, the link between the aldehyde dehydrogenase-2 (ALDH2) genotype and acetaldehyde-derived DNA damage has not yet been explored. We have developed a sensitive and quantitative method for detecting the acetaldehyde-derived DNA adducts, N(2)-ethyl-2'-deoxyguanosine (N(2)-Et-dG), alpha-S- and alpha-R-methyl-gamma-hydroxy-1,N(2)-propano-2'-deoxyguanosine (alpha-S-Me-gamma-OH-PdG and alpha-R-Me-gamma-OH-PdG), and N(2)-(2,6-dimethyl-1,3-dioxan-4-yl)-deoxyguanosine (N(2)-Dio-dG), by using liquid chromatography electrospray tandem mass spectrometry (LC/ESI-MS/MS) and stable-isotope internal standards. We determined the DNA adducts in 44 blood DNA samples from Japanese alcoholic patients. The levels of three acetaldehyde-derived DNA adducts, N(2)-Et-dG, alpha-S-Me-gamma-OH-PdG, and alpha-R-Me-gamma-OH-PdG, were significantly higher in alcoholics with the ALDH2 1/2 2 genotype compared to those with the ALDH2 1/2 1 genotype. N(2)-Dio-dG was not detected in any of the DNA samples analyzed. These results provide molecular evidence that the ALDH2 genotype affects the genotoxic damage caused by acetaldehyde.
The epidemiologic evidence support that alcohol intake might be associated with increased colorectal cancer risk. However, the results by anatomic site in the large bowel are inconsistent. We conducted a meta-analysis of prospective cohort studies published between 1990 and June 2005 on the relationship between alcohol intake and colon and rectal cancer. We quantified associations with colon and rectal cancer using meta-analysis of relative risk (RR) associated to the highest versus the lowest category of alcohol intake and meta-analysis of study-specific dose-response slopes using fixed or random effect models depending on the heterogeneity of effects among studies. Sixteen prospective cohort studies including more than 6,300 patients with colorectal cancer were eligible for inclusion. High alcohol intake was significantly associated with increased risk of colon (RR = 1.50; 95% CI = 1.25, 1.79) and rectal cancer (RR = 1.63; 95% CI = 1.35, 1.97) when comparing the highest with the lowest category of alcohol intake, equivalent to a 15% increase of risk of colon or rectal cancer for an increase of 100 g of alcohol intake per week. The relationship did not differ significantly by anatomical site (colon, rectum). Using meta-regression analysis, we identified geographical area where the study was conducted as a possible source of between-study heterogeneity of effects among studies. Lifestyle recommendations for prevention of colorectal cancer should consider limiting alcohol intake.
Diet and vitamin or mineral supplements and risk of renal cell carcinoma in Canada
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