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. 2024 Jul 30;13(7):1718-1726.
doi: 10.21037/tlcr-24-480. Epub 2024 Jul 25.

Age at first sexual intercourse, age at menarche, and age at menopause: a mendelian randomization study on lung cancer risk

Yifan Liu  1 , Xinxin Ying  1 , Yao Li  1 , Xingyu Zhu  1 , Wangwei Jing  2 , Xiaohong Wang  3 , Zhengfu He  1
Affiliations

Age at first sexual intercourse, age at menarche, and age at menopause: a mendelian randomization study on lung cancer risk

Yifan Liu et al. Transl Lung Cancer Res. .

Abstract

Background: There is increasing evidence that sex hormones are involved in the development of lung cancer, but the correlation between the reproductive behavior that changes sex hormone levels and lung cancer is not yet clear. Many previous studies have investigated the association between reproductive factors and lung cancer risk, but the results have been inconsistent. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to explore the potential relationship between age at first sexual intercourse (AFS), age at menarche, and age at menopause, and lung cancer.

Methods: We performed a MR analysis of the data from the genome-wide association study (GWAS) of European ancestry to evaluate the independent effects of three reproductive behaviors on lung cancer overall (LUCA), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and small cell lung cancer (SCLC). We mainly used the inverse-variance weighting method for the MR analysis. Sensitivity was determined by a MR-pleiotropy residual sum and outlier analysis, a weighted median analysis, a MR-Egger analysis, and a leave-one-out analysis.

Results: The MR analysis results revealed that older AFS had a causal relationship with LUCA [odds ratio (OR) =0.6283, 95% confidence interval (CI): 0.4959-0.7961, P=0.0001), LUAD (OR =0.7042, 95% CI: 0.4967-0.9984, P=0.049), and LUSC (OR =0.6231, 95% CI: 0.4386-0.8853, P=0.0083).

Conclusions: Our results revealed a causal relationship between older AFS and a lower risk of lung cancer. Our findings emphasize the importance of providing sex education, as early sexual intercourse may have undesirable effects. In addition, early psychological treatment is also essential.

Keywords: Mendelian randomization analysis (MR analysis); Reproductive behaviors; age at first sexual intercourse (AFS); lung cancer; lung cancer prevention.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-480/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
MR study flow diagram to determine the causal effect of three exposures on lung cancer, The dashed lines indicate potential pleiotropic or direct causal effects between the variables that may violate MR assumptions. MR, Mendelian randomization; SNPs, single nucleotide polymorphisms; AFS, age at first sexual intercourse; IVW, inverse-variance weighted; WM, weighted median.
Figure 2
Figure 2
Relationship of three exposures with lung cancer by a MR analysis. Sensitivity was determined by the listed methods. MR, mendelian randomization; OR, odds ratio; CI, confidence interval; AFS, age at first sexual intercourse; SNPs, single nucleotide polymorphisms.
See this image and copyright information in PMC

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