Infertility and Risk of Breast, Gynecologic, and Colorectal Cancer

项目摘要/摘要 在美国，10%-15%的夫妇承受着不孕不育的负担。患有不孕症的女性可能会增加 罹患慢性病的风险，包括癌症。多种途径都与这种联系有关 不孕症和癌症风险之间的关系，包括激素异常(例如，患有 排卵性不孕症)和炎症环境(例如，患有 子宫内膜异位症、输卵管因素不孕症)。此外，不孕不育的潜在病因可能会导致癌症。 风险，一些不孕不育的诊断具有较高的癌症风险(例如，子宫内膜异位症和卵巢癌风险) 以及其他风险较低的疾病(如排卵性不孕症和乳腺癌)。关于协会的研究 不孕不育和癌症之间的关系大多局限于小型临床研究、机制研究和 短期随访的登记研究；所有这些研究主要集中在绝经前癌症 在种族/族裔多样性有限的人群中开展了这项研究。此外， 对不孕症诊断的差异没有引起足够的重视。因此，在我们的 关于不孕症和癌症风险之间复杂联系的知识。拟议的研究将 重点关注乳腺癌、卵巢癌、子宫内膜癌和结直肠癌，因为这些癌症已经建立了荷尔蒙 和炎性危险因素，并有一些最高的发病率和死亡率。我们将对数据进行分析 在妇女健康倡议(WHI)中收集的数据--这是一个大型的有效队列，其中包括超过160,000 绝经后妇女，随访期长(超过25年)，种族/民族多样性强 样本人口。使用这些二次数据，我们将确定经历过 与从未经历过不孕的产妇相比，不孕症患者罹患特定癌症的风险更高。 以及这种风险如何随着不孕不育的诊断而变化。因为大约六分之一的女性经历不孕不育和 近85%的女性癌症发生在绝经后，这对公共卫生有重大影响 了解绝经后不孕症病史与癌症发病风险的关系 女人。

Project Summary/Abstract Infertility burdens 10-15% of couples in the United States. Women suffering from infertility may be at increased risk of chronic diseases, including cancer. A variety of pathways have been implicated in the association between infertility and cancer risk, including aberrant hormonal (e.g., excess androgens among women with ovulatory infertility) and inflammatory environments (e.g., excess inflammation among women with endometriosis, tubal factor infertility). Additionally, the underlying etiology of the infertility may modify cancer risk, with some infertility diagnoses conferring higher cancer risk (e.g., endometriosis and ovarian cancer risk) and others conferring lower risk (e.g., ovulatory infertility and breast cancer). Research on the association between infertility and cancer has been limited to mostly small clinical studies, mechanistic studies, and registry studies with short durations of follow-up; all of which focus predominately on premenopausal cancer incidence and have been conducted among populations with limited racial/ethnic diversity. Moreover, insufficient attention has been paid to differences in infertility diagnosis. Thus, there are significant gaps in our knowledge regarding the complex association between infertility and cancer risks. The proposed research will focus on breast, ovarian, endometrial, and colorectal cancers, as these cancers have established hormonal and inflammatory risk factors and have some of the highest incidence and mortality. We will analyze the data collected in the Women’s Health Initiative (WHI)—a large, validated cohort that includes over 160,000 postmenopausal women with long follow-up duration (over 25 years), and strong racial/ethnic diversity within the sample population. Using these secondary data, we will determine whether women who have experienced infertility have increased risk for specific cancers compared to parous women who never experienced infertility and how this risk varies by infertility diagnosis. As approximately one in six women experience infertility and nearly 85% of cancers in women occur after menopause, there are critical public health implications for understanding the relationship between infertility history and risk of these cancers among postmenopausal women.