• Yan Zhang, Huaying Liang, Jun Cheng, Abira A Choudhry, Xin Zhou, Guowei Zhou, Yiqun Zhu, Dianwu Li, Fengyu Lin, Qinyu Chang, Danrong Jing, Xiang Chen, Pinhua Pan, and Hong Liu.
• Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China; Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China; Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China; Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China. Electronic address: zhangy4290@csu.edu.cn.
• Chest. 2024 Jul 1; 166 (1): 226239226-239.

BackgroundSeveral characteristics distinguish lung cancer in female patients from that in male patients, with adenocarcinoma being more prevalent in female patients and occurring more frequently in female patients who do not smoke. Uncertainty surrounds the relationship between female-specific reproductive factors and lung cancer risk.Research QuestionAre sex-specific reproductive factors associated with risk of lung cancer in different genetic risk groups and histologic types?Study Design And MethodsA Cox proportional hazard model was used to evaluate the association between multiple reproductive factors and the risk of lung cancer developing in a prospective cohort study involving 273,190 female individuals from the UK Biobank. Subgroup analyses stratified by age, smoking status, BMI, genetic risk, and histologic subtype were conducted to emphasize the modification effects further.ResultsA total of 1,182 cases of lung cancer in female patients were recorded over a median follow-up period of 12.0 years in the cohort study. In multivariable-adjusted models, early menarche (age ≤ 11 years: hazard ratio [HR], 1.22; 95% CI, 1.03-1.46), early menopause (age ≤ 46 years: HR, 1.49; 95% CI, 1.19-1.86), a shorter reproductive span (≤ 32 years: HR, 1.42; 95% CI, 1.18-1.71; and 33-35 years: HR, 1.24; 95% CI, 1.00-1.53), and early age at first birth (age ≤ 20 years: HR, 1.63; 95% CI, 1.33-2.01) were associated with a higher risk of lung cancer. Stratified analysis revealed that several reproductive factors, including early age at menopause, shortened reproductive span, and early age at first birth, showed a substantially stronger relationship with an elevated risk of lung cancer, particularly of lung adenocarcinoma, in populations with high genetic risk and more detrimental behaviors.InterpretationEarly age at menopause, a shortened reproductive life span, and early age at first birth were associated with higher risks of lung cancer, particularly of lung adenocarcinoma, in a subpopulation with higher genetic susceptibility and detrimental behaviors. The evidence provided by this study emphasizes the significance of screening for multiple reproductive factors to prevent lung cancer among female individuals.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

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