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.