Cholesterol and the risk of grade-specific prostate cancer incidence: evidence from two large prospective cohort studies with up to 37 years' follow up

Abstract

Background: High cholesterol may be a modifiable risk factor for prostate cancer but results have been inconsistent and subject to potential "reverse causality" where undetected disease modifies cholesterol prior to diagnosis.

Methods: We conducted a prospective cohort study of 12,926 men who were enrolled in the Midspan studies between 1970 and 1976 and followed up to 31st December 2007. We used Cox-Proportional Hazards Models to evaluate the association between baseline plasma cholesterol and Gleason grade-specific prostate cancer incidence. We excluded cancers detected within at least 5 years of cholesterol assay.

Results: 650 men developed prostate cancer in up to 37 years' follow-up. Baseline plasma cholesterol was positively associated with hazard of high grade (Gleason score≥8) prostate cancer incidence (n = 119). The association was greatest among men in the 2nd highest quintile for cholesterol, 6.1 to < 6.69 mmol/l, Hazard Ratio 2.28, 95% CI 1.27 to 4.10, compared with the baseline of < 5.05 mmol/l. This association remained significant after adjustment for body mass index, smoking and socioeconomic status.

Conclusions: Men with higher cholesterol are at greater risk of developing high-grade prostate cancer but not overall risk of prostate cancer. Interventions to minimise metabolic risk factors may have a role in reducing incidence of aggressive prostate cancer.

Figure 1

Functional form of the association of cholesterol with the relative hazard of Gleason 8 to 10 prostate cancers estimated in a Cox proportional hazards model using age as the time axis. The function was fitted using restricted cubic splines with three knots (X). The function was standardized such that the HR was 1 at the mean cholesterol level of the lowest quintile. Dotted lines indicate the 95% confidence intervals.