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.

We aim to determine if 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 (GWAS) conducted on alcohol consumption (N=~1.5 million individuals), breast (N_case=122,977) and ovarian cancer (N_case=25,509). We 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 behavior. We 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.

We did not find any evidence to support for a causal association between alcohol consumption and risk of breast cancer [OR_drinks/week=1.01 (0.85-1.21), P=0.89; OR_AUD=1.04 (95%CI: 0.89-1.21), P=0.62; OR_AUDIT-C=1.07 (0.90-1.28), P=0.44]; neither with its subtypes including ER-positive and ER-negative breast cancer, using any of the three alcohol-related exposures. For ovarian cancer, however, we identified a reduced risk with alcohol consumption, where a borderline significance was found for AUDIT-C but not for drinks/week or AUC [OR_drinks/week=0.83 (0.63-1.10), P=0.19; OR_AUD=0.92 (0.83-1.01), P=0.08; OR_AUDIT-C=0.83 (0.71-0.97), P=0.02]. The effect attenuated to null excluding SNPs associated with potential confounders [OR_drinks/week=0.81(0.53-1.21), P=0.31; OR_AUD=0.96(0.78-1.18), P=0.68; OR_AUDIT-C=0.89(0.68-1.16), P=0.38].

We do 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 our findings are needed, when large-scale alcohol consumption GWAS results become available.