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.