Alcohol consumption and risk of breast and ovarian cancer: A Mendelian randomization study

Alcohol consumption has been found to increase the risk of breast cancer in observation studies, yet it remains unknown if alcohol is related to other hormone-dependent cancers such as ovarian cancer. No Mendelian randomization (MR) studies have been performed to assess a potential causal relationship between alcohol use and risk of breast and ovarian cancer.
Researchers aimed to determine whether alcohol consumption is causally associated with the risk of female hormone-dependent cancers, by using summary level genetic data from the hitherto largest genome-wide association studies conducted on alcohol consumption (with 1.5 million individuals), breast and ovarian cancer (122,977 and 25,509 cases respectively). The researchers examined three different alcohol intake exposures, drinks per week (drinks/week), alcohol use disorder (AUD) and age-adjusted alcohol use disorder identification test (AUDIT-C), to reflect the general and harmful drinking behaviour. The researchers constructed updated and stronger instruments using ninety-nine drinks/week-related SNPs, nine AUD-related SNPs and thirteen AUDIT-C-related SNPs and estimated the causal relationship applying several two-sample MR methods.
The research did not find any evidence to support for a causal association between alcohol consumption and risk of breast cancer, neither with its subtypes including ER-positive and ER-negative breast cancer, using any of the three alcohol-related exposures. For ovarian cancer, a reduced risk with alcohol consumption was identified, where a borderline significance was found for AUDIT-C but not for drinks/week or AUD. The effect attenuated to null excluding SNPs associated with potential confounders.
The researchers conclude that they did not find any compelling evidence in support for a causal relationship between genetically predicted alcohol consumption and risk of breast or ovarian cancer, consistent across three different alcohol-related exposures. Future MR studies validating these findings are needed, when large-scale alcohol consumption GWAS results become available.
Source: Zhu, Jingjing & Jiang, Xia & Niu, Zheng. (2020). Alcohol consumption and risk of breast and ovarian cancer: A Mendelian randomization study. Cancer Genetics. 245.