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.