Effects of personal characteristics on serum CA125, mesothelin, and HE4 levels in healthy postmenopausal women at high-risk for ovarian cancer

Objective: To evaluate if serum levels of candidate ovarian cancer biomarkers vary with individual characteristics of healthy women who are likely candidates for an ovarian cancer screening program. Methods: We analyzed serum CA125, mesothelin, and HE4 levels in a sample of 1.55 healthy postmenopausal women at increased risk for developing ovarian cancer based on personal and family cancer history. Information on reproductive, family and medical histories, lifestyle factors, and anthropometry was collected by self-report. Twenty-two factors were examined using univariate and multiple linear regression models for the three biomarker levels. Results: In the multivariate models, CA125 levels were significantly higher in women who had used talcum powder (P = 0.02) and were lower in women who were parous (P = 0.05). Mesothelin levels were significantly higher in older women (P = 0.01) and lower in heavier women (P = 0.03). HE4 levels were higher in older women (P = 0.001) and in women who began menstruating at an older age (P = 0.03). Conclusions: CA125, mesothelin, and HE4 levels in healthy, postmenopausal women at increased risk for ovarian cancer are significantly associated with a few ovarian cancer risk factors. Since the effects of these personal characteristics on these serum markers are not large, their incorporation in screening algorithms may be unnecessary. This is true especially if a longitudinal algorithm is used because the marker level at the previous screen reflects personal characteristics such as age, body mass index, and age of menarche. Understanding the influence of personal factors on levels of novel early detection markers in healthy, unaffected women may have clinical utility in interpreting biomarker levels.