Menstrual factors, reproductive history, and risk of lung cancer: a multi-center population-based cohort study in Chinese females

Zhuoyu Yang; Fei Wang; Fengwei Tan; Wei Cao; Yongjie Xu; Chao Qin; Yiwen Yu; Liang Zhao; Yan Wen; Zheng Wu; Yadi Zheng; Yunyong Liu; Lianzheng Yu; Donghua Wei; Dong Dong; Ji Cao; Shaokai Zhang; Shipeng Yan; Ning Wang; Xianzhen Liao; Lingbin Du; Jiang Li; Ni Li; Wanqing Chen; Jie He

doi:10.21037/tlcr-21-552

Menstrual factors, reproductive history, and risk of lung cancer: a multi-center population-based cohort study in Chinese females

Transl Lung Cancer Res. 2021 Oct;10(10):3912-3928. doi: 10.21037/tlcr-21-552.

Authors

Zhuoyu Yang^#¹, Fei Wang^#¹, Fengwei Tan^#², Wei Cao¹, Yongjie Xu¹, Chao Qin¹, Yiwen Yu¹, Liang Zhao¹, Yan Wen¹, Zheng Wu¹, Yadi Zheng¹, Yunyong Liu^{3

4}, Lianzheng Yu⁵, Donghua Wei⁶, Dong Dong⁷, Ji Cao⁸, Shaokai Zhang⁹, Shipeng Yan¹⁰, Ning Wang¹¹, Xianzhen Liao¹⁰, Lingbin Du¹², Jiang Li¹, Ni Li^{1

13

14}, Wanqing Chen¹, Jie He²

Affiliations

¹ Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ Department for Cancer Prevention and Treatment of Liaoning Province/Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China.
⁴ Division of Pneumoconiosis School of Public Health, China Medical University, Shenyang, China.
⁵ Department of Noncommunicable Chronic Disease Prevention, Liaoning Center for Disease Control and Prevention, Shenyang, China.
⁶ Cancer Department of Physical Examination, Anhui Provincial Cancer Hospital, Hefei, China.
⁷ Office of Cancer Prevention and Treatment, Xuzhou Cancer Hospital, Xuzhou, China.
⁸ Department of Experimental Pathology, Tumor Hospital of Guangxi Medical University, Nanning, China.
⁹ Department of Cancer Epidemiology, Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Henan Engineering Research Center of Cancer Prevention and Control, Henan International Joint Laboratory of Cancer Prevention, Zhengzhou, China.
¹⁰ Department of Cancer Prevention and Control, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
¹¹ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, China.
¹² Department of Cancer Prevention, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)/IBMC, Chinese Academy of Sciences, Hangzhou, China.
¹³ Chinese Academy of Medical Sciences Key Laboratory for National Cancer Big Data Analysis and Implement, Beijing, China.
¹⁴ Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.

^# Contributed equally.

Abstract

Background: Female menstrual and reproductive factors, as remarkable indicators of hormone effect, were hypothesized to be associated with lung cancer risk, whereas the existed epidemiological evidence was inconsistent. Our study aims to investigate the association between menstrual and reproductive factors and lung cancer risk based on the Chinese Lung Cancer Screening Program.

Methods: This study was based on a large-scale multi-center population cohort across China recruiting individuals aged 40-74 years old between 2013-2018. Cox regression model was applied to estimate the HRs and 95% CIs. Restricted cubic spline (RCS) analysis was used to estimate dose-response relationships and test for nonlinear associations.

Results: Among 553,434 female participants, 1,529 incident lung cancer cases were identified with a median follow-up of 3.61 years. With adjustment for multiple covariates and all significant hormonal factors, elevated lung cancer risk was associated with later age (15, or ≥16 years) at menarche (HR =1.27, 95% CI: 1.04-1.56; HR =1.45, 95% CI: 1.19-1.76), later age (25-29, or ≥30 years) at first live birth (HR =1.27, 95% CI: 1.13-1.43; HR =1.23, 95% CI: 1.00-1.51), and benign breast disease history (HR =1.25, 95% CI: 1.10-1.41). For postmenopausal females specifically, surgical menopause (HR =1.62; 95% CI: 1.29-2.05) and other surgeries on the reproductive system (HR =1.19; 95% CI: 1.01-1.40) both appeared to be predictive of elevated lung cancer risk. Concerning age at menopause, a nonlinear association was observed (P-nonlinear =0.0126). Increased lung cancer risk was observed among females with age at menopause especially above 50. Although we observed no significant associations between longer time (≥13 months) of breastfeeding and lung cancer risk among all participants (HR =0.86; 95% CI: 0.71-1.04), significant decreased adenocarcinoma risk (HR =0.65; 95% CI: 0.53-0.81) was noted among nonsmoking females.

Conclusions: Our findings add some support for the role of menstrual and reproductive factors in lung carcinogenesis. However, these relationships were complex, and required further investigations addressing the biological mechanisms.

Keywords: Lung cancer; cohort study; hormones; population-based.