Infertility and Risk of Breast, Gynecologic, and Colorectal Cancer

项目概要/摘要 在美国，10-15%的夫妇患有不孕症。患有不孕症的女性可能会增加 慢性疾病的风险，包括癌症。各种途径都与这种关联有关 不孕症和癌症风险之间的关系，包括异常的激素（例如，女性中过量的雄激素 排卵性不孕症）和炎性环境（例如，女性过度炎症 子宫内膜异位症、输卵管因素不孕症）。此外，不孕症的潜在病因可能会改变癌症 风险，一些不孕症诊断赋予更高的癌症风险（例如，子宫内膜异位症和卵巢癌风险） 以及其它赋予较低风险的（例如，排卵性不孕症和乳腺癌）。协会研究 不孕症和癌症之间的关系仅限于大多数小型临床研究，机制研究， 随访时间短的登记研究;所有这些研究主要关注绝经前癌症 发病率，并已在种族/民族多样性有限的人群中进行。此外，委员会认为， 对不孕症诊断的差异重视不够。因此，我们在这方面存在重大差距。 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激素依赖性。 和炎症危险因素，并具有一些最高的发病率和死亡率。我们会分析数据 收集在妇女健康倡议（WHI）-一个大的，验证队列，包括超过160，000 随访时间长（超过25年）的绝经后女性， 抽样人口。利用这些次要数据，我们将确定是否有过 与从未经历过不孕症的经产妇女相比，不孕症增加了患特定癌症的风险 以及这种风险如何随不孕症诊断而变化。大约六分之一的妇女患有不孕症， 近85%的女性癌症发生在绝经后，这对公共卫生有重要意义。 了解绝经后妇女不孕症史与这些癌症风险之间的关系 妇女

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.