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Int J Cancer. 2017 Jul 15;141(2):309-323. doi: 10.1002/ijc.30750. Epub 2017 May 10.

Menstrual and reproductive factors and lung cancer risk: A pooled analysis from the international lung cancer consortium.

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Université Paris Saclay, Université Paris Sud, UVSQ, CESP, INSERM, Villejuif, France.
Risk Assessment Department (DER), French Agency for Food, Environmental and Occupational Health Safety (ANSES), Maisons-Alfort, France.
Harvard TH Chan School of Public Health, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
Karmanos Cancer Institute and Department of Oncology, Wayne State University School of Medicine, Detroit, MI.
CRCHUM (Centre de recherche du CHUM) and Department of Social and Preventive Medicine, Université de Montréal, QC, Canada.
Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
Norris Cotton Cancer Center, Geisel School of Medicine, Dartmouth College Lebanon, NH.
Epidemiology and Biostatistics Department, Memorial Sloan Kettering Cancer Center, NY.
Department of Surgery, Memorial Sloan Kettering Cancer Center, NY.
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
Department of Clinical Sciences and Community Health, Università degli Studi di Milano and IRCCS Ca' Granda Foundation, Milan, Italy.


Many clinical features of lung cancer are different in women and men. Sex steroid hormones exert effects in nonreproductive organs, such as the lungs. The association between menstrual and childbearing factors and the risk of lung cancer among women is still debated. We performed a pooled analysis of eight studies contributing to the International Lung Cancer Consortium (4,386 cases and 4,177 controls). Pooled associations between menstrual or reproductive factors and lung cancer were estimated using multivariable unconditional logistic regression. Subgroup analyses were done for menopause status, smoking habits and histology. We found no strong support for an association of age at menarche and at menopause with lung cancer, but peri/postmenopausal women were at higher risk compared to premenopausal (OR 1.47, 95% CI 1.11-1.93). Premenopausal women showed increased risks associated with parity (OR 1.74, 95% CI 1.03-2.93) and number of children (OR 2.88, 95% CI 1.21-6.93 for more than 3 children; p for trend 0.01) and decreased with breastfeeding (OR 0.54, 95% CI 0.30-0.98). In contrast, peri/postmenopausal subjects had ORs around unity for the same exposures. No major effect modification was exerted by smoking status or cancer histology. Menstrual and reproductive factors may play a role in the genesis of lung cancer, yet the mechanisms are unclear, and smoking remains the most important modifiable risk factor. More investigations in large well-designed studies are needed to confirm these findings and to clarify the underlying mechanisms of gender differences in lung cancer risk.


case-control studies; lung neoplasms; menopause; reproductive history; women

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