The causal effects of genetically predicted alcohol consumption on endometrial cancer risk

Endometrial cancer is a common gynaecological tumour in females with an increasing incidence over the past few decades. Alcohol consumption has been linked to the occurrence of various cancers; However, epidemiological studies have shown inconsistent associations between alcohol consumption and EC risk. In order to avoid the influence of potential confounding factors and reverse causality in traditional epidemiological studies, Mendelian randomization (MR) analysis was used to test whether there is a causal relationship between alcohol consumption and Endometrial cancer.
MR analysis was conducted using publicly available summary-level data from genome-wide association studies (GWAS). Fifty-seven single nucleotide polymorphisms (SNPs) were extracted as instrumental variables for alcohol exposure from the GWAS and Sequencing Consortium of Alcohol and Nicotine GWAS summary data involving 941,287 participants of European ancestry. SNPs for EC were obtained from the Endometrial Cancer Association Consortium, the Endometrial Cancer Epidemiology Consortium, and the UK Biobank, involving 121,885 European participants.
An increase of 1 standard deviation of genetically predicted log-transformed alcoholic drinks per day was associated with a 43% reduction in Endometrial cancer risk [odds ratio (OR) = 0.57, 95% confidence interval (CI) 0.41-0.79]. Subgroup analysis of Endometrial cancer revealed that alcohol consumption was a protective factor for endometrioid endometrial cancer (OR = 0.56, 95% CI 0.38-0.83) but not for non-endometrioid endometrial cancer (OR = 1.36, 95% CI 0.40-4.66). The consistent results of sensitivity analyses indicated the reliability of the causal estimates. Additionally, alcohol consumption was associated with decreased human chorionic gonadotropin (HCG) and insulin-like growth factor 1 (IGF1) levels.
This MR study suggests that genetically predicted alcohol consumption is a protective factor for Endometrial cancer, particularly for endometrioid endometrial cancer, and this protective effect may be mediated through the reduction of HCG and IGF1.
Source: Yang J, Qu X, Zheng AJ, Jiang F, Chang H, Zhang JR, Yan LJ, Ning P. The causal effects of genetically predicted alcohol consumption on endometrial cancer risk from a Mendelian randomization study. Sci Rep. 2024 Feb 12;14(1):3478. doi.org/10.1038/s41598-024-53926-z