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| Association between age at first sexual intercourse and gynecologic malignant tumors: a Mendelian randomization study |
| JIANG Shudi1, GUO Ting1, LING Junjun1, REN Jie1, ZHANG Liang1,2
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1. The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, China;
2. Chongqing Liangjiang New Area Traditional Chinese Medicine Hospital, Chongqing 401123, China |
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Abstract Objective To examine the casual association between age at first sexual intercourse and gynecologic malignant tumors using Mendelian randomization (MR) approach. Methods The single nucleotide polymorphisms (SNPs) associated with age at first sexual intercourse were obtained from a meta-analysis of genome-wide association study (GWAS), and the SNPs related to gynecologic malignant tumors (ovarian cancer, endometrial cancer, cervical cancer), and their subtypes were sourced from the IEU OpenGWAS database. Using age at first sexual intercourse as the exposure and gynecologic malignant tumors as the outcome, a MR analysis was performed with the inverse-variance weighted (IVW) method. Heterogeneity was assessed using Cochran's Q test, horizontal pleiotropy was evaluated using MR-Egger regression and MR-PRESSO test, and bias was examined using funnel plots. Results The Mendelian randomization analysis demonstrated that younger age at first sexual intercourse was significantly associated with an increased risk of low-grade serous ovarian carcinoma (OR=0.553, 95%CI: 0.335-0.911), cervical cancer (OR=0.674, 95%CI: 0.466-0.974), endometrial cancer (OR=0.854, 95%CI: 0.730-0.999), and endometrioid carcinoma (OR=0.830, 95%CI: 0.690-0.998). No statistical association was found between the age at first sexual intercourse and ovarian cancer, high-grade serous ovarian cancer, mucinous ovarian cancer, endometrioid ovarian cancer, or non-endometrioid ovarian cancer (all P>0.05). Sensitivity analysis showed no evidence of undetected instrumental variable heterogeneity or horizontal pleiotropy (all P>0.05), and the funnel plot indicated no presence of bias. Conclusion Younger age at first sexual intercourse may be associated with an increased risk of certain gynecologic malignant tumors, highlighting the need to strengthen adolescent sex education.
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Received: 28 November 2024
Revised: 03 April 2025
Published: 23 May 2025
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