Plasma total cholesterol concentration and risk of higher‐grade prostate cancer: A nested case‐control study and a dose‐response meta‐analysis

Abstract Our previous publication found an increased risk of higher‐grade (Gleason sum ≥7) prostate cancer for men with high total cholesterol concentration (≥200 mg/dl) in the Health Professionals Follow‐up Study (HPFS). With additional 568 prostate cancer cases, we are now able to investigate this association in more detail. For the nested case‐control study, we included 1260 men newly diagnosed with prostate cancer between 1993 and 2004, and 1328 controls. For the meta‐analyses, 23 articles studied the relationship between total cholesterol level and prostate cancer incidence were included. Logistic regression models and dose‐response meta‐analysis were performed. An increased risk of higher‐grade (Gleason sum ≥4 + 3) prostate cancer for high vs low quartile of total cholesterol level was observed in the HPFS (OR multivariable = 1.56; 95% CI = 1.01‐2.40). This finding was compatible with the association noted in the meta‐analysis of highest vs lowest group of total cholesterol level, which suggested a moderately increased risk of higher‐grade prostate cancer (Pooled RR =1.21; 95%CI: 1.11‐1.32). Moreover, the dose‐response meta‐analysis indicated that an increased risk of higher‐grade prostate cancer occurred primarily at total cholesterol levels ≥200 mg/dl, where the RR was 1.04 (95%CI: 1.01‐1.08) per 20 mg/dl increase in total cholesterol level. However, total cholesterol concentration was not associated with the risk of prostate cancer overall either in the HPFS or in the meta‐analysis. Our primary finding, as well as the result of the meta‐analysis suggested a modest increased risk of higher‐grade prostate cancer, at total cholesterol concentrations exceeding 200 mg/dl.