Reproductive factors and lung cancer risk in never-smoking women: a prospective cohort study
- 1Cancer Institute in Hebei Province, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050000 China
- 2Department of Epidemiology and Statistics, School of Public Health, Hebei Province Key Laboratory of Environment and Human Health, Hebei Medical University, Shijiazhuang, China
- 3Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
Abstract
Background: The association between endogenous estrogen and lung cancer in never-smoking women remains unclear. This study investigated the associations of various reproductive factors, as proxies for cumulative estrogen exposure, with lung cancer risk among never-smoking women from a lung cancer screening cohort.
Methods: Associations between reproductive factors and lung cancer risk were evaluated using multivariable logistic regression and restricted cubic splines. Mediation analysis assessed the mediating role of body mass index (BMI). Subgroup analyses were stratified by baseline characteristics. Robustness was verified through propensity score matching and inverse probability of treatment weighting.
Results: The study included 155,103 never-smoking women, identifying 657 incident lung cancer cases. Early menarche (< 13 years: OR, 1.41; 95% CI, 1.06–1.87), a shorter reproductive span (≤ 32 years: OR, 1.25; 95% CI, 1.02–1.54), and parity (≥ 1) (OR, 2.02; 95% CI, 1.16–3.52) were associated with increased risk. Later age at first birth (≥ 30 years) (OR, 0.63; 95% CI, 0.41–0.98) and a history of benign breast disease (OR, 0.64; 95% CI, 0.47–0.87) were inversely associated with lung cancer risk, with age at first birth showing a non-linear dose-response relationship. Mediation analyses suggested a potential role of BMI in these associations. Stratified analyses revealed significant effect modification by age, BMI, and clinical history.
Conclusion: Reproductive factors are associated with lung cancer risk among never-smoking women. Integrating reproductive histories into routine lung cancer screening programs will facilitate more precise risk stratification.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16429-w.
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BibTeX
@article{nie2026reproductive,
title = {{Reproductive factors and lung cancer risk in never-smoking women: a prospective cohort study}},
author = {Yaxiong Nie and Di Liang and Yuqing Jin and Maogang Gao and Jiaai Li and Shize Wang and Siqi Wu and Jin Shi and Yanyu Liu and Xin Su and Saijin Cui and Yutong He},
journal = {BMC Cancer},
year = {2026},
month = jun,
doi = {10.1186/s12885-026-16429-w},
url = {https://doi.org/10.1186/s12885-026-16429-w},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Reproductive factors and lung cancer risk in never-smoking women: a prospective cohort study
AU - Yaxiong Nie
AU - Di Liang
AU - Yuqing Jin
AU - Maogang Gao
AU - Jiaai Li
AU - Shize Wang
AU - Siqi Wu
AU - Jin Shi
AU - Yanyu Liu
AU - Xin Su
AU - Saijin Cui
AU - Yutong He
PY - 2026
DA - 2026/06/01
JO - BMC Cancer
DO - 10.1186/s12885-026-16429-w
UR - https://doi.org/10.1186/s12885-026-16429-w
AB - Background: The association between endogenous estrogen and lung cancer in never-smoking women remains unclear. This study investigated the associations of various reproductive factors, as proxies for cumulative estrogen exposure, with lung cancer risk among never-smoking women from a lung cancer screening cohort. Methods: Associations between reproductive factors and lung cancer risk were evaluated using multivariable logistic regression and restricted cubic splines. Mediation analysis assessed the mediating role of body mass index (BMI). Subgroup analyses were stratified by baseline characteristics. Robustness was verified through propensity score matching and inverse probability of treatment weighting. Results: The study included 155,103 never-smoking women, identifying 657 incident lung cancer cases. Early menarche (< 13 years: OR, 1.41; 95% CI, 1.06–1.87), a shorter reproductive span (≤ 32 years: OR, 1.25; 95% CI, 1.02–1.54), and parity (≥ 1) (OR, 2.02; 95% CI, 1.16–3.52) were associated with increased risk. Later age at first birth (≥ 30 years) (OR, 0.63; 95% CI, 0.41–0.98) and a history of benign breast disease (OR, 0.64; 95% CI, 0.47–0.87) were inversely associated with lung cancer risk, with age at first birth showing a non-linear dose-response relationship. Mediation analyses suggested a potential role of BMI in these associations. Stratified analyses revealed significant effect modification by age, BMI, and clinical history. Conclusion: Reproductive factors are associated with lung cancer risk among never-smoking women. Integrating reproductive histories into routine lung cancer screening programs will facilitate more precise risk stratification. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16429-w.
SN - 1471-2407
ER -