Project 1 Title: Chronic Medical Conditions and CA125 Levels Among Women Without Ovarian Cancer. Project 2 Title: Statin Therapy and Association With Ovarian Cancer Risk in the New England Case Control (NEC) Study

Abstract

Project 1 Abstract: Background: Randomized trials using the biomarker CA125, with or without pelvic ultrasound, have failed to show a clear benefit of general population screening for ovarian cancer. In part this may be due to a lack of information about conditions, besides ovarian cancer, that can alter CA125 levels and affect specificity or sensitivity. We evaluated the association between common medical conditions and CA125 levels among women without ovarian cancer. Methods: We used data and specimens from 2,004 women without ovarian cancer who participated in the New England Case Control study between 1992 and 2008. Participants completed in-person interviews and donated blood samples at enrollment. We measured CA125 using the CA125II assay and calculated the association between medical conditions and log-transformed CA125 using linear regression. Results: The median age of participants was 53 years and 1,119 (56%) were postmenopausal. The average CA125 level was 14.5 units/mL for premenopausal and 11.7 for postmenopausal women. Among premenopausal women, CA125 was significantly lower for women with colon polyps (p=0.06) and hysterectomy (p=0.01) and significantly higher with endometriosis (p=0.05). CA125 was also significantly higher in premenopausal women with coronary artery disease (CVD) (p<0.01, n=2 cases) but not among postmenopausal with CVD (n=79). Further, among postmenopausal women, CA125 was significantly lower for women with osteoporosis, hypercholesterolemia, and osteoarthritis (p=0.03, 0.02 and 0.01 respectively) and higher for women with a history of inflammatory bowel disease (p=0.04). Conclusion: Several chronic diseases are associated with CA125, which could influence the interpretation of CA125 in the context of ovarian cancer screening. Project 2 Abstract: Background: Statins are widely used to lower blood cholesterol and reduce risk for cardiovascular diseases; but attention has recently focused on a role in cancer prevention or therapy. Here, we present data from a large case-control study addressing whether statin use can lower the risk for epithelial ovarian cancer (EOC). Methods: Between 1992 and 2008, data, including medications used for at least 6 months, was collected from 2040 cases with EOC and 2100 matched controls without the disease who participated in the New England Case-Control study. We used unconditional logistic regression controlling for matching factors and potential confounders to examine the association between statin use and the risk for EOC. Results: Overall, women who use statins had 32% lower risk of ovarian cancer compared to non-users (OR 0.68, 95% CI: 0.55 – 0.85) adjusting for the matching factors and other covariates. The reduced risk was most apparent in women: taking a “lipophilic statin”; who began use after age 49, and who had used them 2 - 4 years. Statin use was associated with lower risks for both serous and non-serous histologic subtypes with strongest effect seen for mucinous subtypes (OR 0.40, 95% CI: 0.19 – 0.85). The association did not appear to be confounded by indications for use of statins or medications used concomitantly. Conclusion: In this case-control study, statins were found to lower the risk for both serous and non-serous EOC and especially mucinous EOC.