Age at menarche and epithelial ovarian cancer risk: A meta-analysis and Mendelian randomization study.
Age at menarche (AAM) was found to be associated with ovarian cancer risk in previous observational studies. However, the causality of this association remains unclear. Here, after systematic meta-analyses, we performed two-sample Mendelian randomization (MR) analyses to evaluate the causal effect of AAM in epithelial ovarian cancer (EOC) etiology. We performed meta-analyses including 11 410 cases and 1 163 117 noncases to quantitatively evaluate the association between AAM and ovarian cancer risk. In MR analyses, we used 25 single nucleotide polymorphisms (SNPs) associated with AAM for Chinese and 390 SNPs for Europeans as instrumental variables. MR estimates were calculated using inverse-variance weighted methods from 1044 cases and 1172 controls in a Chinese genome-wide association study and validated by the Ovarian Cancer Association Consortium and Consortium of Investigators of Modifiers of BRCA1/2 studies with 29 396 cases and 68 502 controls of European ancestry. In meta-analyses, we observed an inverse association (odds ratio [OR] = 0.96, 95% confidence interval [CI] = 0.93 to 1.00, P = 0.036) between per year older AAM and ovarian cancer risk in case-control studies, but no association was observed in cohort studies. In MR analyses, the OR of EOC risk per year increase in AAM was 0.81 (95% CI = 0.67 to 0.97, P = 0.026) in Chinese and 0.94 (95% CI = 0.90 to 0.98, P = 0.003) in Europeans, respectively. Our study supports a causal association between AAM and EOC risk.
['Yang|Huijun|H|', 'Dai|Hongji|H|', 'Li|Lian|L|', 'Wang|Xin|X|0000-0001-9325-3194', 'Wang|Peishan|P|', 'Song|Fengju|F|0000-0003-1542-0828', 'Zhang|Ben|B|', 'Chen|Kexin|K|0000-0003-1010-8093']
D000367:Age Factors D000077216:Carcinoma, Ovarian Epithelial D016022:Case-Control Studies D005260:Female D055106:Genome-Wide Association Study D006801:Humans D008572:Menarche D057182:Mendelian Randomization Analysis D016017:Odds Ratio D010051:Ovarian Neoplasms D018570:Risk Assessment D012307:Risk Factors
menarche ovarian cancer meta-analysis Mendelian randomization analysis