Epidemiology of moderate alcohol consumption and breast cancer: Association or causation?

Epidemiological studies have been used to show associations between modifiable lifestyle factors and the incidence of breast cancer. Alcohol consumption is one factor that has been reported in multiple studies and meta-analyses over the past decades. However, associative epidemiological studies that are interpreted as evidence that even moderate alcohol consumption increases breast cancer incidence have been inconsistent and controversial. Besides complications due to confounding factors that may be difficult to assess, the validity of such an association depends critically on the quality of information on respondents’ alcohol consumption, both in quantities consumed and drinking profile, throughout an individual’s history relevant to disease onset and progression. Although epidemiology applies statistical approaches to identify associative relations, such studies by themselves are less suitable to identify causal relationships. Establishing causality requires additional information and knowledge.
A review by Samir Zahari and Jan B Hoek highlights both the broad scope of possible molecular mechanisms that may contribute to the onset or progression of cancers of the breast, as well as current ignorance of the detailed underlying processes and their regulation that dictates the outcome. Some of these potential processes influenced by alcohol use are likely to require relatively high levels of drinking and prolonged exposure. However, other mechanisms, such as those mediated by various epigenetic controls, are as yet poorly characterised and, as a result, remain unpredictable. A survey of the multiple epidemiological studies and meta-analyses also highlights a substantial variability that exists in the relative risk estimates, which are particularly difficult to interpret when light to moderate drinking frequencies are considered.
The authors comment that “alcohol has a social function that is important in many people’s lives. For the vast majority of drinkers this social function is associated with occasional or moderate drinking. The relative risk of negative consequences, including the relative risk of
developing breast cancer, is therefore an issue that has to be weighed against these positives. Most observational epidemiological studies are in agreement that heavy drinking carries significant and diverse negative consequences and should be actively avoided. However, the negative consequences of light or moderate drinking are minimal, even in the majority of studies that show a detectable odds ratio for cancer or other diseases at these lower levels”.
In this context, the important question is then whether a particular individual carries a higher risk than the general population as a consequence of specific susceptibilities that may vary from one person to another. Zahari and Hoek argue, therefore, that it may be more useful to be able to advise individual patients on specific vulnerabilities, either in their susceptibility to potential damaging effects of alcohol (e.g., those expressing the defective ALDH2*2 isoform) or with significant risk factors for developing breast cancer, BRCA1 or BRCA2 mutations the impact of which may increase their susceptibility to other potential risk factors. In addition, women with a positive family history of breast cancer, or are using contraceptive pills or hormone replacement therapy may be at higher risk.
They point to the efforts of the transdisciplinary field of molecular pathological epidemiology (MPE) to evaluate possible causal relationships, if any, of alcohol consumption and breast cancer. A wider application of the principles of MPE to this field would, they suggest, constitute a giant step that could enhance our understanding of breast cancer and multiple modifiable risk factors, a step that would be particularly suited to the era of “personalized medicine”. Further, it would facilitate the development of early detection tools that would help distinguish relatively innocuous indicators from more significant malignancies, and assist in the development of more individually targeted treatment.
Source: Epidemiology of Moderate Alcohol Consumption and Breast Cancer: Association or Causation? Samir Zakhari and Jan B. Hoek. Cancers 2018, 10(10), 349. Full text article.