Associations Between Sex-Specific Reproductive Factors and Risk of New-Onset Lung Cancer Among Female Patients

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; Hong Liu

doi:10.1016/j.chest.2023.11.014

Associations Between Sex-Specific Reproductive Factors and Risk of New-Onset Lung Cancer Among Female Patients

Chest. 2023 Nov 15:S0012-3692(23)05709-4. doi: 10.1016/j.chest.2023.11.014. Online ahead of print.

Authors

Yan Zhang¹, Huaying Liang², Jun Cheng³, Abira A Choudhry⁴, Xin Zhou², Guowei Zhou⁵, Yiqun Zhu², Dianwu Li², Fengyu Lin², Qinyu Chang², Danrong Jing⁶, Xiang Chen⁷, Pinhua Pan⁸, Hong Liu⁶

Affiliations

¹ 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.
² 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; 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.
³ Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Department of Molecular and Integrative Physiology, The University of Michigan, Ann Arbor, MI, USA.
⁵ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.
⁶ Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.
⁷ Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Furong Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.
⁸ 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; Furong Laboratory, 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.

PMID: 37977264
DOI: 10.1016/j.chest.2023.11.014

Abstract

Background: Several 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 question: Are sex-specific reproductive factors associated with risk of lung cancer in different genetic risk groups and histologic types?

Study design and methods: A 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.

Results: A 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.

Interpretation: Early 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.

Keywords: genetic risk; lung cancer; menopause; non-small cell lung cancer; reproductive factors.