Abstract B92: Serum total and HDL cholesterol and risk of prostate cancer

Abstract

Abstract Background: There has been growing support for the hypothesis that low cholesterol may protect against prostate cancer with a poorer prognosis. Studies suggest a decreased risk of high-grade prostate cancer in men with lower circulating total cholesterol, and that statin drugs may protect against aggressive prostate cancer. Confirmation of these findings in additional populations and examination of lipoprotein subfractions is needed. We prospectively examined prostate cancer risk and serum total and HDL cholesterol in the ATBC Study cohort. Methods: The ATBC Study was a randomized controlled trial conducted among male smokers in Finland to determine the effects of α-tocopherol and β-carotene supplements on cancer incidence. Fasting blood samples were collected at baseline (1985 — 1988), and total and HDL cholesterol were measured for all participants (n=29,133). Cohort follow-up continues through the Finnish Cancer Registry and the Register of Causes of Death. Cox proportional hazards models were used to estimate the relative risk of overall (n=2,041), high stage (≥ TNM stage III or AJC stage 3; n=412), high grade (Gleason sum ≥ 7; n=231), aggressive (either high stage or high grade; n=461), and non-aggressive (neither high stage nor high grade; n=829) prostate cancer by categories of total (<200, 200 — <240, ≥240 mg/dL) and HDL (<40, 40 — <60, ≥60 mg/dL) cholesterol. Multivariable models adjusted for age, serum α-tocopherol, family history of prostate cancer, education, and urban residence. Further adjustment for the following factors did not alter the results: α-tocopherol and β-carotene supplementation group, serum β-carotene, cigarettes per day, years smoked, physical activity, marital status, and intake of total energy, total fat, fruits and vegetables, red meat, alcohol, vitamin A, vitamin D, and calcium. Results: Men with high serum total cholesterol were at increased risk of prostate cancer, particularly high stage disease (≥240 vs. <200 mg/dl: HR=1.26, 95% CI 0.92 — 1.71, p-trend = 0.03). Stratification by follow-up time showed that the increased risk of prostate cancer for men with higher total cholesterol was limited to cases diagnosed at least 10 years after baseline. After excluding the first 9 years of follow-up, men with higher serum total cholesterol were at an increased risk of overall (≥240 vs. <200: HR=1.22, 95% CI 1.03 — 1.44, p-trend=0.01) and advanced-stage (≥240 vs. <200: HR=1.85, 95% CI 1.13 — 3.03, p-trend=0.05) prostate cancer. Higher HDL cholesterol appeared related to decreased risk of prostate cancer, overall and all clinical subtypes, throughout the follow-up period. Conclusion: In this population of male smokers with a low prevalence of PSA screening, high serum total cholesterol was associated with an increased risk of advanced prostate cancer, but only among cases diagnosed at least 10 years after baseline. Further, there was a suggestion that high HDL cholesterol reduced the risk of all clinical subtypes of prostate cancer. These results support previous studies and, indirectly, support the hypothesis that statin drugs may reduce the risk of prostate cancer with a poorer prognosis by lowering cholesterol concentrations. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B92.