Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Fertil Steril. 2023 Jul;120(1):134-142. doi: 10.1016/j.fertnstert.2023.02.028. Epub 2023 Feb 25.
To investigate the association between infertility and the incidence of invasive cancer.
Prospective cohort study (1989-2015).
Not applicable.
PATIENT(S): A total of 103,080 women aged 25-42 years in the Nurses' Health Study II who were cancer-free at baseline (1989).
INTERVENTION(S): The infertility status (failure to conceive after 1 year of regular, unprotected sex) and causes of infertility were self-reported at baseline and biennial follow-up questionnaires.
MAIN OUTCOME MEASURE(S): 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 postmenopausal breast) or non-obesity-related (all other cancers). We fit the Cox proportional-hazards models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between infertility and cancer incidence.
RESULT(S): 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 and other risk factors, women who reported infertility had a higher risk of developing cancer than 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 (postmenopausal breast, endometrial, and ovarian cancers; HR, 1.17; 95% CI, 1.06-1.29) and was stronger among women who first reported 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 < .001).
CONCLUSION(S): A history of infertility may be associated with the risk of developing obesity-related reproductive cancers; further study is needed to elucidate the underlying mechanisms.
探讨不孕与侵袭性癌症发病的相关性。
前瞻性队列研究（1989-2015 年）。
不适用。
护士健康研究 II 中年龄在 25-42 岁之间、基线时无癌症（1989 年）的 103080 名女性。
不孕状况（规律无保护性生活 1 年后仍未怀孕）和不孕原因在基线和每两年一次的随访问卷中进行自我报告。
癌症诊断通过病历复查确定，并分为肥胖相关癌症（结直肠癌、胆囊癌、肾癌、多发性骨髓瘤、甲状腺癌、胰腺癌、食管癌、胃癌、肝癌、子宫内膜癌、卵巢癌和绝经后乳腺癌）和非肥胖相关癌症（所有其他癌症）。我们使用 Cox 比例风险模型估计不孕与癌症发病风险之间的风险比（HR）和 95%置信区间（CI）。
在 2149385 人年的随访期间，26208 名女性报告有不孕史，我们记录了 6925 例侵袭性癌症病例。调整体重指数和其他危险因素后，与从未不孕的孕妇相比，报告不孕的女性癌症发病风险更高（HR，1.07；95%CI，1.02-1.13）。这种关联在肥胖相关癌症中更强（HR，1.13；95%CI，1.05-1.22；vs. 非肥胖相关癌症，HR，0.98；95%CI，0.91-1.06），特别是肥胖相关生殖系统癌症（绝经后乳腺癌、子宫内膜癌和卵巢癌；HR，1.17；95%CI，1.06-1.29），并且在更早报告不孕的女性中更强（≤25 岁，HR，1.19；95%CI，1.07-1.33；26-30 岁，HR，1.11；95%CI，0.99-1.25；>30 岁，HR，1.07；95%CI，0.94-1.22；P 趋势<.001）。
不孕史可能与肥胖相关生殖系统癌症的发病风险相关；需要进一步研究阐明潜在机制。
