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

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.

Clinicopathological characteristics of ovarian carcinomas associated with endometriosis.

INTRODUCTION: Substantial histopathology data provide evidence that endometriosis might be viewed as a precursor lesion of endometrioid and clear cell carcinoma of the ovary, via intermediary atypical borderline lesions. Also, genes involved in both endometriosis and epithelial ovarian cancer have been shown to play a role in the pathogenesis of endometriosis-associated ovarian carcinoma. MATERIAL AND METHODS: A retrospective study of 17 cases of ovarian carcinomas associated with endometriosis, diagnosed between 2000 and 2009, at Aretaieion Hospital of University of Athens, is presented. 10/17 cases in this study (58.8%) were clear cell carcinomas (CCC), 6/17 cases (35.3%) were endometrioid adenocarcinomas (EAC) and 1/17 cases (5.9%) was a serous carcinoma associated with ovarian endometriosis. Patients's age was 27-76 years (mean age 58 years). Typical ovarian endometriosis was documented in 8/17 (47%) of the tumors. In 9/17 cases, areas of fibrosis or cystic lesions infiltrated by iron-laden macrophages and endometrial-like stroma, consistent with endometriosis, were observed. CONCLUSION: In comparison with common epithelial ovarian cancers, CCC and EACs of the ovary were presented at earlier stages. Cytoreductive surgical treatment is critical in order to plan appropriate post-operative management.