A prospective cohort study of infertility and cancer incidence.

Overview

abstract

OBJECTIVE: To investigate the association between infertility and incidence of invasive cancer. DESIGN: Prospective cohort study (1989-2015). SUBJECTS: 103,080 women aged 25-42 years in the Nurses' Health Study II who were cancer free at baseline (1989). EXPOSURE: Infertility status (failure to conceive after one year of trying) and causes of infertility were self-reported at baseline and biennial follow-up questionnaires. MAIN OUTCOME MEASURES: Cancer diagnosis was confirmed through medical record review and classified as obesity-related (colorectal, gallbladder, kidney, multiple myeloma, thyroid, pancreatic, esophageal, gastric, liver, endometrial, ovarian, and post-menopausal breast) or non-obesity-related (all other cancers). We fit Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between infertility and cancer incidence. RESULTS: During 2,149,385 person-years of follow-up, 26,208 women reported a history of infertility, and we documented 6,925 incident invasive cancer cases. After adjusting for body mass index (BMI) and other risk factors, women reporting infertility had a greater risk of developing cancer compared to gravid women without a history of infertility (HR=1.07; 95% CI, 1.02-1.13). This association was stronger among obesity-related cancers (HR=1.13; 95% CI, 1.05-1.22; vs non-obesity-related cancers, HR=0.98; 95% CI, 0.91-1.06), and in particular, obesity-related reproductive cancers (post-menopausal breast, endometrial, and ovarian cancer; HR=1.17, 95% CI, 1.06-1.29) and was stronger among women first reporting infertility earlier in life (≤25 years: HR=1.19, 95% CI, 1.07-1.33; 26-30 years: HR=1.11, 95% CI, 0.99-1.25; >30 years: HR=1.07, 95% CI, 0.94-1.22; P trend<0.001). CONCLUSION: History of infertility may be associated with risk of developing obesity-related reproductive cancers; further study is needed to elucidate underlying mechanisms.