Dataset Information

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

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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC11304150 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Liu Yifan Y Ying Xinxin X Li Yao Y Zhu Xingyu X Jing Wangwei W Wang Xiaohong X He Zhengfu Z

Translational lung cancer research 20240725 7

<h4>Background</h4>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 betwee ...[more]

PMID: 39118897

Similar Datasets

Project description:BackgroundHormonal reproductive factors have been suggested to play an important role in the etiology of rheumatoid arthritis (RA), an autoimmune inflammatory disorder affecting primarily women. We conducted a two-sample Mendelian randomization (MR) study examining three relevant exposures, age at menarche (AAM), age at natural menopause (ANM), and age at first birth (AFB) with the risk of RA.MethodsWe collected summary statistics from the hitherto largest GWAS conducted in AAM (N = 329,345), ANM (N = 69,360), AFB (N = 251,151), and RA (Ncase = 14,361, Ncontrol = 43,923), all of European ancestry. We constructed strong instruments using hundreds of exposure-associated genetic variants and estimated causal relationship through different MR approaches including an inverse-variance weighted method, an MR-Egger regression and a weighted median method. We conducted a multivariable MR to control for pleiotropic effect acting in particular through obesity and socioeconomic status. We also performed important sensitivity analyses to verify model assumptions.ResultsWe did not find any evidence in support for a causal association between genetically predicted reproductive factors and risk of RA (ORper-SD increment in AAM = 1.06 [0.98-1.15]; ORper-SD increment in ANM = 1.05 [0.98-1.11], OR per-SD increment in AFB = 0.85 [0.65-1.10]). Results remained consistent after removing palindromic SNPs (ORper-SD increment in AAM = 1.06 [0.97-1.15], ORper-SD increment in ANM = 1.05 [0.98-1.13], ORper-SD increment in AFB = 0.81 [0.61-1.07]) or excluding SNPs associated with potential confounding traits (ORper-SD increment in AAM = 1.03 [0.94-1.12], ORper-SD increment in ANM = 1.04 [0.95-1.14]). No outlying instrument was identified through the leave-one-out analysis.ConclusionsOur MR study does not convincingly support a casual effect of reproductive factors, as reflected by age at menarche, age at menopause, and age at first birth, on the development of RA. Despite the largely augmented set of instruments we used, these instruments only explained a modest proportion of phenotypic variance of exposures. Our knowledge regarding this topic is still insufficient and future studies with larger sample size should be designed to replicate or dispute our findings.

Project description:A trend towards earlier menarche in women has been associated with childhood factors (e.g. obesity) and hypothesised environmental exposures (e.g. endocrine disruptors present in household products). Observational evidence has shown detrimental effects of early menarche on various health outcomes including adult lung function, but these might represent spurious associations due to confounding. To address this we used Mendelian randomization where genetic variants are used as proxies for age at menarche, since genetic associations are not affected by classical confounding. We estimated the effects of age at menarche on forced vital capacity (FVC), a proxy for restrictive lung impairment, and ratio of forced expiratory volume in one second to FVC (FEV1/FVC), a measure of airway obstruction, in both adulthood and adolescence. We derived SNP-age at menarche association estimates for 122 variants from a published genome-wide meta-analysis (N = 182,416), with SNP-lung function estimates obtained by meta-analysing three studies of adult women (N = 46,944) and two of adolescent girls (N = 3025). We investigated the impact of departures from the assumption of no pleiotropy through sensitivity analyses. In adult women, in line with previous evidence, we found an effect on restrictive lung impairment with a 24.8 mL increase in FVC per year increase in age at menarche (95% CI 1.8-47.9; p = 0.035); evidence was stronger after excluding potential pleiotropic variants (43.6 mL; 17.2-69.9; p = 0.001). In adolescent girls we found an opposite effect (-56.5 mL; -108.3 to -4.7; p = 0.033), suggesting that the detrimental effect in adulthood may be preceded by a short-term post-pubertal benefit. Our secondary analyses showing results in the same direction in men and boys, in whom age at menarche SNPs have also shown association with sexual development, suggest a role for pubertal timing in general rather than menarche specifically. We found no effect on airway obstruction (FEV1/FVC).

Project description:BackgroundIncreasing observational studies have indicated that hormonal reproductive factors were associated with ovarian cyst, a common gynecological disease. A two-sample Mendelian randomization (MR) was carried out by investigating the causality of reproductive factors including age at first birth (AFB), age at natural menopause (ANM), and age at menarche (AAM), and the risk of ovarian cyst (OC).MethodSummary statistics were collected from a large genome-wide association study (GWAS), and we used a two-sample MR study to clarify the causal association between the exposure of AFB (N = 542,901), ANM (N = 69,360), and AAM (N = 29,346) and the outcome of the OC (N case = 20,750, N control = 107,564). We separately selected 51, 35, and 6 single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for assaying the influence of AFB, ANM, and AAM on OC, respectively. Then, the causal relationship was tested through multiple approaches including an inverse-variance weighted method, an MR-Egger regression, and a weighted median method. In addition, the MR-PRESSO method was also used to verify the horizontal pleiotropy. Subsequently, we adjust the confounders for MR design.ResultsThe MR analysis results showed that AFB was negatively associated with the OC (IVW Beta: -0.09, OR: 0.91, 95% CI: 0.86-0.96, p = 0.00185), and the greater AAM decreased the risk of OC (IVW Beta: -0.10, OR: 0.91, 95% CI: 0.82-0.99, p = 0.0376). However, ANM has a positive correlation with the OC (IVW Beta: 0.05, OR: 1.05, 95% CI: 1.03-1.08, p = 8.38 × 10-6). After adjusting BMI, alcohol intake frequency, and ever smoked, we also obtained a negative relationship between AFB and OC (p < 0.005). Meanwhile, we adjusted weight, alcohol intake frequency, and height, and then found a causal relationship between older AMN and an increased risk of OC (p < 0.005).ConclusionA causal effect of reproductive factors on the development of OC, affected by AFB, ANM, and AAM, was found convincingly. After adjusting the confounders, we also successfully found the substantial causal effect of younger AFB, younger AAM, and older ANM on an increased risk of OC.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets