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Hormonal factors and the risk of breast, endometrial, and ovarian cancers among nulliparous women

Principal Investigator

Name
Sara Schonfeld

Institution
NCI, DCEG, REB

Email
schonfes@mail.nih.gov

About this CDAS Project

Study
PLCO (Learn more about this study)

Project ID
2007-0064

Initial CDAS Request Approval
Feb 15, 2008

Title
Hormonal factors and the risk of breast, endometrial, and ovarian cancers among nulliparous women

Summary
Based on studies largely consisting of parous women, endogenous and exogenous sources of hormonal exposures have been implicated in the etiology of breast, endometrial and ovarian cancers (1, 2). Nulliparity, the status of having borne no children, is associated with a small to moderate increased risk (relative risk (RR): 1.2-2.5) of breast (3, 4), endometrial (5, 6) and ovarian (7, 8) cancers. A complicated set of hormone and hormone-related changes occurring during pregnancy are hypothesized to explain the long-term protection afforded by parity against breast, endometrial and ovarian cancers and may explain the observed increased risk associated with nulliparity (9-11). Small sample sizes of nulliparous women within individual study populations limit efforts to study the association between hormonal factors and cancer risk within this population. We propose to pool data from four NCI cohort studies to study the association between endogenous (age at menarche, age at menopause, and body mass index (BMI)) and exogenous (oral contraceptive (OC) use and menopausal hormone therapy (HT) use) hormonal factors and the risk of breast, endometrial and ovarian cancers among postmenopausal, nulliparous women. The four studies include The Breast Cancer Detection Demonstration Project Follow up Study (BCDDP), the NIH-AARP Diet and Health Study (AARP), The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), and the United States Radiologic Technologist (USRT) Study. We estimate that together these cohorts include over 25,000 postmenopausal, nulliparous women, in whom approximately 1090 breast, 255 endometrial and 135 ovarian incident cancer cases have been reported to date. In addition, we will use these datasets to evaluate the validity of the Gail Model, a widely-used breast cancer risk prediction model, for use among nulliparous women.

Aims

Guiding the proposed research is the underlying hypothesis that endogenous and exogenous hormonal factors are associated with the risk of breast, endometrial and ovarian cancers among postmenopausal, nulliparous women. Given that each individual cohort has a relatively limited number of nulliparous women in which to study this question, we propose to pool data from both arms of the PLCO screening trial and three additional cohorts (AARP, BCDDP and USRT).
• Aim 1: Estimate the relative risks of breast (1a), endometrial (1b) and ovarian (1c) cancers associated with a set of endogenous (age at menarche, age at menopause, and body mass index) and exogenous (oral contraceptive use and menopausal hormone therapy use) hormonal factors among postmenopausal, nulliparous women.
• Aim 2: Examine whether the Gail model is valid for use among nulliparous women by estimating the calibration and discrimination.

Collaborators

Clara Bodelon (DCEG)
Patricia Hartge (DCEG)
Kala Visvanathan (JHBSPH)
James Lacey (DCEG)
Ruth Pfeiffer (DCEG)
Nicolas Wentzensen (DCEG)

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