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

Author:

Ben Khedher Soumaya1ORCID,Neri Monica1,Papadopoulos Alexandra2,Christiani David C.3,Diao Nancy3,Harris Curtis C4,Olivo‐Marston Susan4,Schwartz Ann G.5,Cote Michele5,Koushik Anita6,Siemiatycki Jack6,Landi Maria Teresa7,Hung Rayjean J.8,McLaughlin John8,Duell Eric J9ORCID,Andrew Angeline S.9,Orlow Irene10,Park Bernard J.11,Brenner Hermann1213,Saum Kai‐Uwe12,Pesatori Angela C.14,Stücker Isabelle1

Affiliation:

1. Université Paris Saclay, Université Paris Sud, UVSQ, CESP, INSERM Villejuif France

2. Risk Assessment Department (DER), French Agency for Food Environmental and Occupational Health Safety (ANSES), Maisons‐Alfort France

3. Harvard TH Chan School of Public Health Massachusetts General Hospital/Harvard Medical School Boston MA

4. Laboratory of Human Carcinogenesis Center for Cancer Research, National Cancer Institute Bethesda MD

5. Karmanos Cancer Institute and Department of Oncology Wayne State University School of Medicine Detroit MI

6. CRCHUM (Centre de recherche du CHUM) and Department of Social and Preventive Medicine Université de Montréal QC Canada

7. Department of Health and Human Services, Division of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health Bethesda MD

8. Lunenfeld‐Tanenbaum Research Institute, Sinai Health System Toronto ON Canada

9. Norris Cotton Cancer Center, Geisel School of Medicine Dartmouth College Lebanon NH

10. Epidemiology and Biostatistics Department Memorial Sloan Kettering Cancer Center NY

11. Department of Surgery Memorial Sloan Kettering Cancer Center NY

12. Division of Clinical Epidemiology and Aging Research German Cancer Research Center (DKFZ) Heidelberg Germany

13. Division of Preventive Oncology German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany

14. Department of Clinical Sciences and Community Health Università degli Studi di Milano and IRCCS Ca' Granda Foundation Milan Italy

Abstract

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.

Funder

National Cancer Institute

Canadian Cancer Society Research Institute

National Institutes of Health

Publisher

Wiley

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