Serum low-density lipoprotein levels correlate with survival in advanced stage epithelial ovarian cancers

Abstract

Objective Recent data suggest patients with epithelial ovarian cancers on statin therapy have improved survival. We have hypothesized that statins influence ovarian cancer outcome through alteration of lipoprotein profiles, and sought to determine correlations between lipoprotein levels and survival in women with advanced stage disease. Methods After IRB approval, we identified patients with stage IIIC/IV epithelial ovarian cancer with banked prediagnostic fasting serum. Serum was assayed for levels of total cholesterol (TC), high-density lipoprotein (HDL), and triglycerides (TG). LDL was calculated by subtraction of TG/5 and HDL from TC. Data were examined using Fisher's exact, Kaplan–Meier, and Cox regression analyses. Results One hundred thirty-two patients were studied. Twenty-six percent of patients had elevated LDL; 18% had elevated TC; 32% had elevated TG; and 48% had elevated HDL. No univariate associations were identified between elevated TC, HDL, TG, LDL and age, stage IV disease, high grade, or optimal cytoreduction. Median progression-free survival for patients with normal LDL levels was 27 months, compared to 12 months for patients with elevated LDL (p = 0.0004). Overall disease-specific survival was longer for patients with normal LDL levels (59 months) compared to those with elevated LDL (51 months, p = 0.04). Multivariate analysis indicated that LDL retained significance as an independent predictor of survival, after controlling for age, stage, grade, and suboptimal cytoreduction (p = 0.003). Conclusions These data suggest LDL is a significant predictor of clinical outcome, and warrant the further study of lipoproteins and statins on epithelial ovarian cancer biology.

Association of Lipid Metabolism with Ovarian Cancer

“…Li et al 33 reported elevated tg levels (32%) in ovarian cancer patients, but previously, Ostroumova et al 34 reported lower tg levels.…”

Association Between Statin Use and Endometrial Cancer Survival

“…Effect of statin and aspirin use on development of deep vein thrombosis, as a contributor to mortality, has failed to show a decreased risk of thromboembolic events, so it is unlikely that the survival benefit is related to prevention of thrombosis. 23 Li et al 24 have reported that decreased LDL was associated with survival in advanced-stage epithelial ovarian cancers of predominately papillary serous histologic types. These data suggest biological plausibility for a mechanism related to lipid metabolism as an explanation of the effect of statin therapy on mortality from cancer.…”

Apolipoprotein A-I (apoA-I) and apoA-I mimetic peptides inhibit tumor development in a mouse model of ovarian cancer

“…The Health Professionals Followup Study identified statin users to have a significantly lower risk of metastatic and fatal disease in prostate cancer patients (33). In women with advanced-stage epithelial ovarian cancers, a statistically significant longer time to progression and improved overall survival was observed for those patients also on statin therapy (34) and, more recently, LDL was demonstrated to be a significant predictor of clinical outcome in advanced epithelial ovarian cancer patients (35). In another study, paraoxonase activity (a key anti-oxidant protein associated with HDL) correlated inversely with stage, grade, and CA-125 level of ovarian cancer (36).…”