Association of smoking, alcohol, and coffee consumption with the risk of ovarian cancer and prognosis: a mendelian randomization study

Abstract

Objective Currently, the association between smoking, alcohol, and coffee intake and the risk of ovarian cancer (OC) remains conflicting. In this study, we used a two-sample mendelian randomization (MR) method to evaluate the association of smoking, drinking and coffee consumption with the risk of OC and prognosis. Methods Five risk factors related to lifestyles (cigarettes per day, smoking initiation, smoking cessation, alcohol consumption and coffee consumption) were chosen from the Genome-Wide Association Study, and 28, 105, 10, 36 and 36 single-nucleotide polymorphisms (SNPs) were obtained as instrumental variables (IVs). Outcome variables were achieved from the Ovarian Cancer Association Consortium. Inverse-variance-weighted method was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl). Results The two-sample MR analysis supported the causal association of genetically predicted smoking initiation (OR: 1.15 per SD, 95%CI: 1.02–1.29, P = 0.027) and coffee consumption (OR: 1.40 per 50% increase, 95%CI: 1.02–1.93, P = 0.040) with the risk of OC, but not cigarettes per day, smoking cessation, and alcohol consumption. Subgroup analysis based on histological subtypes revealed a positive genetical predictive association between coffee consumption and endometrioid OC (OR: 3.01, 95%CI: 1.50–6.04, P = 0.002). Several smoking initiation-related SNPs (rs7585579, rs7929518, rs2378662, rs10001365, rs11078713, rs7929518, and rs62098013), and coffee consumption-related SNPs (rs4410790, and rs1057868) were all associated with overall survival and cancer-specific survival in OC. Conclusion Our findings provide the evidence for a favorable causal association of genetically predicted smoking initiation and coffee consumption with OC risk, and coffee consumption is linked to a greater risk of endometrioid OC.

Endometriosis-Associated Ovarian Cancer: From Molecular Pathologies to Clinical Relevance

“…Besides hyperestrogenism and endometrial cysts, oxidative stress and inflammation are discussed as contributors to malignant transformation [17,28]. Therefore, other risk factors include exposure to environmental toxins, including dioxins [29,30], phthalates [31], alcohol [32] and coffee consumption [33], and smoking [34], as well as improper nutritional habits [35,36]. Finally, genetic predisposition has a large influence on the transition from benign endometriosis to malign ovarian cancer.…”

Most Relevant Genetic, Hormonal, and Environmental Factors in Ovarian Cancer Development – A Literature Review

“…DNAm alterations are the early step in ovarian carcinogenesis [91], which is why there is a possible association between drinking alcohol and the development of epithelial ovarian cancer. Despite all, these days, there are more studies describing no such relation [90,92,93]. Moreover, there is some evidence showing a decreasing risk of ovarian cancer connected with higher red wine consumption [93].…”

Causal effects of hypertensive disorders of pregnancy on future gynecologic tumors: A two‐sample Mendelian randomization study

“…This results in efficacious randomization of high or low genetic risks for diseases, thus minimizing the possibility of confusion and reverse causality, akin to RCTs. Summary data from genome‐wide association studies (GWAS) are more readily available and typically extensive for two‐sample MR analysis, which serves to strengthen genetic interpretation of IVs on exposure and enhances the precision and dependability of analysis outcomes 16 . Consequently, this study aims to perform a two‐sample MR analysis utilizing pooled data from GWAS to explore the relationship between HDPs and the risks of ovarian, cervical, endometrial, and breast cancer, as well as uterine fibroids.…”