Association of coffee and caffeine consumption with risk and prognosis of endometrial cancer and its subgroups: a Mendelian randomization

Ziyu Chen; Chaosheng Liu; Jing Wu; Fandou Kong

doi:10.3389/fnut.2023.1291355

Association of coffee and caffeine consumption with risk and prognosis of endometrial cancer and its subgroups: a Mendelian randomization

Front Nutr. 2023 Nov 14:10:1291355. doi: 10.3389/fnut.2023.1291355. eCollection 2023.

Authors

Ziyu Chen^#¹, Chaosheng Liu^#², Jing Wu¹, Fandou Kong¹

Affiliations

¹ Department of Gynecology and Obstetrics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
² Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.

^# Contributed equally.

Abstract

Background: Previous studies have not established potential causal associations between coffee and caffeine consumption in endometrial cancer (EC) and its subgroups. Therefore, we used a two-sample MR method to assess the causal association between coffee and caffeine consumption and EC risk. We also evaluated the association between these genetically predicted exposures and EC prognosis.

Materials and methods: This study used 12 and two independent single-nucleotide polymorphisms (SNPs) associated with coffee and caffeine consumption as instrumental variables at a genome-wide significance level of p < 5 × 10^-8. The EC Association Consortium (ECAC) performed a genome-wide association study (GWAS) analysis of 12,906 cases and 108,979 controls. FinnGen Consortium performed a GWAS analysis of 1,967 EC cases and 167,189 controls. The primary technique we employed was inverse-variance weighted, followed by the weighted median, MR-Egger regression, and MR robust adjusted profile score methods. We used the MR pleiotropy residual sum, Outlier test, and MR-Egger regression to assess Outlier and pleiotropic variants. We also conducted a sensitivity analysis through the leave-one-out method.

Results: Genetically predicted coffee consumption was not associated with EC and its subgroups in the ECAC, and the association was consistent in the FinnGen consortium. After excluding eight SNPs with confounding factors, the study performed sensitivity analyses, delivering consistent results. We also observed that caffeine consumption was not correlated with EC risk. As confirmed by MR analysis, selected SNPs determined that most do not significantly impact the likelihood of developing EC.

Conclusion: Our study indicated no convincing evidence supports coffee and caffeine consumption causing EC or impacting its prognosis. More studies are needed to validate the results.

Keywords: Mendelian randomization (MR); caffeine consumption; coffee consumption; endometrial cancer (EC); endometrioid histology (EH).

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.