Alcohol-related Cancer Risk Research Articles

Alcohol is not Safe even at Light Amounts.

There is undeniable evidence that alcohol is harmful to health. An increasing concern for alcohol users is underestimating or ignoring its health effects. Some justify their alcohol use by stating that a few drinks may even be good for the health by disregarding a possible future alcohol addiction and dependence problems, while for others it serves as a social gathering necessity. Is alcohol good, bad or ugly? Many studies have shown that moderate to high alcohol intake significantly increases the risk of developing cancers. The National Institute of Health released a warning about the increased risk of cancer for heavy drinkers. Alcohol can have a direct carcinogenic effect in gastrointestinal cancers and can also have indirect effects via the overexpression of oncogenes in cells, thus triggering the development of cancer. In addition, a co-carcinogenic effect is seen by boosting the carcinogenic properties of other chemicals. Alcohol reduces blood levels of vitamins A and E, zinc, iron and some B vitamins, including folate and thiamin, accounting for the increased risk of cancer. Alcohol suppresses the immune system and makes alcoholics more susceptible to developing cancer. Most of the clinical data examined moderate to high alcohol intake studies. Therefore, there is no consensus on a safe level of alcohol use (1,2). The risks associated with alcohol use cannot be limited to only cancer. However, it is important to note that the alcohol industry lost a competition recently. Bagnardi et al. (3) recently stayed away from all negative impulses and reported a meta-analysis about light alcohol drinking and cancer. Alcohol consumption increases the risk of oral cavity, pharynx, esophagus, larynx, liver, breast, and colorectal cancer. The level of alcohol consumption was shown to increase the risk of alcohol-related cancer. Prior to this study, most of the data were derived from studies of moderate to high alcohol intake. For the first time, the researchers evaluated the association between light alcohol drinking (up to 1 drink daily) and cancers by evaluating 13,814 non-unique papers identified through a literature search; in total, 222 unique papers were included in the meta-analysis, comprising 92,000 light drinkers and 60,000 non-drinkers with cancer. Even light drinking was associated with the risk of oropharyngeal cancer, esophageal squamous cell cancer and female breast cancer. No absolute safe level of alcohol intake can be endorsed. This study is important because it was published against the alcohol industry and their enormous power against public health (3). Can these study results break the alcohol industry’s defense and its social place to develop a fear of cancer or other alcohol-related diseases, which may also prevent the majority of people from enjoying even an occasional drink? We are not sure, but hopefully it will be beneficial to have people rethink this toxin and fight against alcohol abuse and dependence.

Adherence to the WHO’s Healthy Diet Indicator and Overall Cancer Risk in the EPIC-NL Cohort

BackgroundA healthy dietary pattern defined by international recommendations of the World Health Organisation (WHO) has been shown to reduce overall mortality risk. It is unknown whether this healthy dietary pattern is associated with overall cancer incidence.DesignIn total 35,355 men and women within the Dutch European Prospective Investigation into Cancer and Nutrition-cohort were followed for cancer occurrence. Diet was assessed through a validated food-frequency questionnaire. We computed a dietary score for all participants based on the seven WHO dietary guidelines for the prevention of chronic diseases (Healthy Diet Indicator (HDI)). We used the existing HDI score based on the 1990 WHO guidelines, and adapted it to meet with the 2002 WHO guidelines. Multivariate-adjusted Cox proportional hazards analysis was used to examine the association between adherence to the HDI and subsequent overall cancer risk.ResultsA number of 3,007 new cancers were identified during a mean follow-up of 12.7 years. Adherence to the HDI was not associated with a reduced overall cancer risk. The hazard ratio (HR) of overall cancer associated with a one-point increment of the HDI was 0.96 (95% CI 0.89–1.03) in men, and 1.00 (95% CI 0.96–1.04) in women. Adherence to the HDI was not associated with smoking-related cancer ((HR men: 0.94 (95% CI 0.84–1.04); HR women: 1.00 (95% CI 0.94–1.07)), or alcohol-related cancer ((HR men: 1.02 (95% CI 0.87–1.20); HR women: 1.03 (95% CI 0.98–1.08)).ConclusionsGreater adherence to the WHO’s Healthy Diet Indicator, a dietary pattern for prevention of chronic diseases, was not associated with reduced overall, smoking-related or alcohol-related cancer risk in men or women.

No and low alcohol intake may have differential effects on risk of overall and cause-specific mortality

Dear Sir: We read with great interest the article by Vergnaud et al (1) on the relation between adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) guidelines and risk of death in Europe. This well-crafted, large-scale study conducted in participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort offers valuable data regarding the impact of the WCRF/AICR recommendations on reducing total and cause-specific mortality and suggests that the utility of these guidelines may extend beyond the scope of cancer prevention. We are, however, keen on gaining additional understanding of the results presented in their Table 4: namely, the risk of death associated with alcohol consumption. The authors found that adherence to the WCRF/AICR recommendation for daily alcohol intake (≤2 drinks for men and 1 drink for women) was protective against all-cause mortality in men but not in women. This result was based on a scoring system that operationalized this alcohol-specific guideline into 3 categories of ethanol intake: ≤20, >20 to ≤30, and >30 g/d for men and ≤10, >10 to ≤20, and >20 g/d for women. Among the 257,421 male study participants, the men whose ethanol intake was >20 to ≤30 g/d had a significantly reduced risk of death compared with men whose consumption exceeded 30 g/d (HR: 0.80), as did men who limited their intake to ≤20 g/d compared with the same referent (HR: 0.89). However, significant associations between risk of death and the alcoholic drinks component of the WCRF/AICR recommendations were not observed among the 121,443 female study participants. We are highly curious both to learn whether making the distinction between no and low ethanol intake would alter the results of this analysis and to see the stratification of HRs by cause of death. Whereas it is widely acknowledged that, unlike in cardiovascular disease, the lowest alcohol-related cancer risk is in fact conferred in the absence of alcohol consumption (2), there remains uncertainty regarding whether the protective effect of abstinence on cancer risk translates to survival outcomes. The most current estimate of alcohol-attributable cancer mortality in the United States to our knowledge suggests that alcohol consumption at any level not only increases cancer risk but, more critically, is a major factor behind cancer-related death in men and women (3). Interestingly, the number of alcohol-attributable deaths was highest for female breast cancer in this investigation. A meta-analysis by Bagnardi et al (4) that included 222 articles concerning alcohol consumption and cancer found that light alcohol drinking (≤1 drink/d) was associated with breast cancer death. In contrast and illustrative of the ambiguity related to drinking and cancer mortality, another recent study reported that any alcohol consumption either before or after breast cancer diagnosis had no adverse impact on survival from breast cancer, cardiovascular disease, or other cause, and that moderate consumption may even have a survival benefit (5). The robust data set of Vergnaud et al presents an opportunity for additional analyses that could shed further light on the advantages or lack thereof of teetotaling in the prevention of cancer or other chronic diseases. As such, we appreciate the authors’ consideration of our request that they both reoperationalize the alcohol-specific WCRF/AICR score such that 0 g/d of ethanol intake is assigned its own category and evaluate alcohol-specific mortality by cause of death and share these results.

Legal interventions to reduce alcohol-related cancers

Research and public policy literature on alcohol-related harm predominantly focuses on the impact of alcohol policies over the short term. However, evidence on the effect of interventions on long-term, alcohol-related chronic disease, including cancers, is growing. The experience from tobacco control supports the use of interventions that increase the price of a commodity and restrict its availability in order to reduce consumption and realize long-term health gains. Meanwhile, the negative involvement of the alcohol industry in alcohol policy development is hampering efforts to intervene early and potentially save many lives. As the burden of alcohol-related cancers becomes more apparent, effective alcohol policies should be introduced sooner rather than later. This paper looks at some of the key legal interventions to reduce alcohol consumption, the potential for these interventions to reduce the risk of alcohol-related cancers, and some of the barriers to implementing these interventions. Examples of law reform efforts in Australia, New Zealand and the UK are given, as well as a short discussion of global alcohol policy initiatives.

Abstract 964: Chlormethiazole, an inhibitor of CYP2E1, prevented chemical carcinogen-initiated and alcohol-promoted hepatic carcinongenesis in rats.

Abstract Chronic and excessive alcohol ingestion, a known risk factor of liver cancer, has been shown to upregulate hepatic cytochrome P450 2E1 (CYP2E1), which is associated with the production of reactive oxygen species and carcinogenic acetaldehyde, the activation of procarcinogens as well as the enhanced catabolism of retinoid. Further, treatment with the CYP2E1 inhibitors, including chlormethiazole (CMZ), have been shown to protect against alcohol-induced liver injury. In order to determine whether treatment with CYP2E1 inhibitor protects against diethylnitrosamine (DEN)-initiated, alcohol-promoted carcinogenesis in the liver, we fed rats (n=6) with either an ethanol liquid diet (Lieber-DeCarli diet) or a non-ethanol liquid diet with isocaloric maltodextrin, with or without CMZ (100 mg/kg BW), for a short-term (1 month) and a long-term (10 months). DEN was given as an initiator for hepatic carcinogenesis by i.p. injection of 20 mg DEN/kg BW. Hepatocarcinogenesis was assessed by examining the placental glutathione-s-transferase (p-GST) immunostaining of altered hepatic foci (AHF) and hepatic tumors lesions. Hepatocyte proliferation was assessed by immunohistochemistry for proliferating cellular nuclear antigen and Ki67, as well as cyclin D1. Hepatic expression of TNF-α and activation of NF-κB and CYP2E1 were assessed by either RT-PCR or Western blotting analysis. Hepatic retinol and retinoic acid were analyzed by reverse-phase HPLC. Results showed that CMZ treatment significantly inhibited ethanol-induced AHF formation, CYP2E1 expression and activity, TNF-α mRNA expression, NF-κB activation and hepatocyte proliferation after a 1-month period. After 10-months of treatment, hepatic nodular regenerative hyperplasia, and hepatocellular adenoma and carcinoma were detected in the ethanol-fed rats, but not in the rest of rat groups with the same dose of DEN treatment, including non-ethanol fed rats and ethanol-fed rats with CMZ treatment. In addition, the CMZ treatment prevented alcohol-reduced retinol and retinoic acid in the livers of rats after 1- and 10-months of treatment. These data demonstrate that CYP2E1 inhibitor can counter the tumor-promoting action of ethanol by restoring normal hepatic levels of retinoic acid. In considering the efficacy and complex biological functions of retinoids in human cancer prevention, intervention using CYP2E1 inhibitors that target alcohol-induced CYP2E1, could provide complementary or synergistic protective effects against alcohol-related cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 964.

Alcohol and genetic polymorphisms: effect on risk of alcohol-related cancer

Public health guidelines aim to limit the consumption of alcoholic beverages worldwide and the subsequent health burden. In particular, alcohol consumption is an avoidable risk factor for cancer. In human beings, ethanol in alcoholic drinks is mainly oxidised in the liver by alcohol dehydrogenases to acetaldehyde, and is further detoxified to acetate by aldehyde dehydrogenases. Functional variants in genes involved in alcohol metabolism result in differences between individuals in exposure to carcinogenic acetaldehyde, suggesting a possible interaction of genetic susceptibility and alcohol exposure in cancer. We reviewed available studies of the combined effects of alcohol drinking and genetic polymorphisms on alcohol-related cancer risk. Most available data were for polymorphisms in alcohol and folate metabolism. We give an overview of published studies on the combined effects of alcohol drinking and polymorphisms in genes for alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), cytochrome P450 2E1, and methylene-tetrahydrofolate reductase on the risk of alcohol-related cancer. Current data lend support to a role of polymorphisms ADH1B and ALDH2 combined with alcohol consumption in cancer. Other available data are insufficient or inconclusive, highlighting the need for additional studies.

Alleles of alcohol and acetaldehyde metabolism genes modulate susceptibility to oesophageal cancer from alcohol consumption

Alleles of alcohol and acetaldehyde metabolism genes modulate susceptibility to oesophageal cancer from alcohol consumption

Alcohol-related cancer risk: A toxico kinetic hypothesis

Consumption of alcoholic beverages is an accepted social custom world-wide. This makes its involvement in events contributing to human cancer risk very important. Although it is neither tumorigenic nor genotoxic in animals, ethanol can potentiate the carcinogenic risk associated with certain environmentally present agents. The reasons for such a synergistic action are speculative, but among theories postulated may be ethanol's ability to modify the toxicokinetics/dynamics of carcinogen metabolism. Experiments conducted with rodents and primates support this hypothesis, demonstrating increased exposure of posthepatic organs to nitrosamines when given in combination with ethanol, followed by enhancement of DNA adduct formation and, at least in rodents, of tumor development. In addition, ethanol may induce enzymes responsible for carcinogen activation, including hepatic cytochrome P450 2E1 in rodents and humans, and in lung, kidney, and brain in rodents. Studies have also shown that these effects can extend to the next generation via maternal and in utero fetal exposure. What impact such ethanol-induced modulations have on tumorigenesis during childhood and later stages of life needs to be investigated further.