Alcohol consumption is associated with oxidative stress and an increased risk of carcinoma of the upper aero-digestive tract (UADT). Recently, it has been found that some microorganisms in the human oral cavity may locally metabolize ethanol, forming acetaldehyde, a carcinogenic metabolite of alcohol. In a cohort of patients first visited for UADT cancers, we estimated their alcohol consumption by measuring Ethyl Glucuronide/EtG (a long-lasting metabolite of ethanol) in the hair and carbohydrate-deficient transferrin/CDT (short-term index of alcohol intake) in the serum. Moreover, we analyzed, by culture-based methods, the presence of Neisseria subflava, Streptococcus mitis, Candida albicans, and glabrata (microorganisms generating acetaldehyde) in the oral cavity. According to the EtG values, we correlated drinking alcohol with endogenous oxidative stress and the investigated microorganism's presence. We found that 55% of heavy drinkers presented microorganisms generating acetaldehyde locally. Moreover, we found that the presence of oral acetaldehyde-producing bacteria correlates with increased oxidative stress compared to patients without such bacteria. As for the study of alcohol dehydrogenase gene polymorphisms (the enzyme that transforms alcohol to acetaldehyde), we found that only the "CGTCGTCCC" haplotype was more frequent in the general population than in carcinoma patients. This pilot study suggests the importance of estimating alcohol consumption (EtG), the presence of bacteria producing acetaldehyde, and oxidative stress as risk factors for the onset of oral carcinomas.
BACKGROUND: Moderate to heavy alcohol consumption is associated with an increased risk of breast cancer. The etiologic role of genetic variation in genes involved in ethanol metabolism has not been established, with little information available among women of African ancestry.
METHODS: Our analysis from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium included 2889 U.S. Black women who were current drinkers at the time of breast cancer diagnosis (N cases = 715) and had available genetic data for four ethanol metabolism genomic regions (ADH, ALDH, CYP2E1, and ALDH2). We used generalized estimating equations to calculate genetic effects, gene* alcohol consumption (>/= 7drinks/week vs. < 7/week) interactions, and joint main plus interaction effects of up to 23,247 variants in ethanol metabolism genomic regions on odds of breast cancer.
RESULTS: Among current drinkers, 21% of cases and 14% of controls reported consuming >/= 7 drinks per week. We identified statistically significant genetic effects for rs79865122-C in CYP2E1 with odds of ER- breast cancer and odds of triple negative breast cancer, as well as a significant joint effect with odds of ER- breast cancer (>/= 7drinks per week OR = 3.92, < 7 drinks per week OR = 0.24, p(joint) = 3.74 x 10(-6)). In addition, there was a statistically significant interaction of rs3858704-A in ALDH2 with consumption of >/= 7 drinks/week on odds of triple negative breast cancer (>/= 7drinks per week OR = 4.41, < 7 drinks per week OR = 0.57, p(int) = 8.97 x 10(-5)).
CONCLUSIONS: There is a paucity of information on the impact of genetic variation in alcohol metabolism genes on odds of breast cancer among Black women. Our analysis of variants in four genomic regions harboring ethanol metabolism genes in a large consortium of U.S. Black women identified significant associations between rs79865122-C in CYP2E1 and odds of ER- and triple negative breast cancer. Replication of these findings is warranted.
Single body mass index (BMI) measurements have been associated with increased risk of 13 cancers. Whether life course adiposity-related exposures are more relevant cancer risk factors than baseline BMI (ie, at start of follow-up for disease outcome) remains unclear. We conducted a cohort study from 2009 until 2018 with population-based electronic health records in Catalonia, Spain. We included 2,645,885 individuals aged >/=40 years and free of cancer in 2009. After 9 years of follow-up, 225,396 participants were diagnosed with cancer. This study shows that longer duration, greater degree, and younger age of onset of overweight and obesity during early adulthood are positively associated with risk of 18 cancers, including leukemia, non-Hodgkin lymphoma, and among never-smokers, head and neck, and bladder cancers which are not yet considered as obesity-related cancers in the literature. Our findings support public health strategies for cancer prevention focussing on preventing and reducing early overweight and obesity.
The implementation of primary and secondary preventive strategies is based on the evidence generated by cancer epidemiology, where the identification of risk factors and the description of their prevalence are fundamental to derive estimates on the burden of cancer from different etiologies, typically expressed as the population attributable fraction, which corresponds to the proportion of a cancer that may be prevented by controlling a given risk factor. However, even when cancer finds its etiology in modifiable factors, its prevention through the control of those factors is not always feasible, or it remains suboptimal despite the possibility of reducing the burden. We reviewed selected associations between modifiable risk factors and cancer, including tobacco smoking, occupational exposures, infections, air pollution, alcohol, and diet and obesity, and illustrated examples of both successes and failures in cancer control, underlying how current understanding of the avoidable causes of cancer is incomplete.