ovarian cancer screening in a high risk population
Background: It is well recognized that women with BRCA mutations have a marked increase risk in ovarian cancer. It is now recognized, however, that there are a variety of ‘low-penetrance’ genes that predispose to an increased risk of ovarian cancer. Many of these genes are in the same pathway as the BRCA genes. Therefore mutations in these genes may lead to similar defects in repair of faulty DNA and result in an increased risk of cancer. These are, however, low-penetrance genes, since the relative risk may be increased by 3-5 fold, and not the 10-20 fold increase seen with BRCA mutations. Presumably, there are other genetic or environmental factors that influence expression. It is estimated that up to one third of hereditary breast and ovarian cancers are attributable to these low penetrance genes. Historically, it was generally recommended that patients with a family history of breast or ovarian cancer should undergo annual ovarian cancer screening, given the potential for this modest increase in risk. This recommendation, however, is empirical and not based on any proven reduction in ovarian cancer mortality. The current study proposes to examine the PLCO data with regard to personal history of breast cancer or family history of breast or ovarian cancer. Ovarian cancer stage at diagnosis will be examined and index mortality will be examined as endpoints.
Method: The current proposal will analyze the PLCO data with regard to patient and/or family history and screening group versus usual medical care group.
1. Screening group vs. usual medical care group for patients with personal history of breast cancer; endpoint ovarian cancer stage and mortality.
2. Screening group vs. usual medical care group for patients with family history of breast or ovarian cancer; endpoint ovarian cancer stage and mortality.
3. Screening group vs. usual medical care group for patients with either personal history of breast cancer and/or family history of breast or ovarian cancer; endpoint ovarian cancer stage and mortality.
4. It is unclear whether obesity may inhibit ovarian cancer detection in the usual medical care group, since pelvic examinations are particularly difficult in obese patients. Therefore an additional analysis will be undertaken for the screening group versus usual medical care group with BMI greater than 30 and a personal history of breast cancer and/or family history of breast or ovarian cancer; endpoint ovarian cancer stage and mortality.
Heong Jun Ahn, Ph.D.
University of Hawaii Biostatistics core