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.

Keywords: dose-response meta-analysis; nested case-control study; prostate cancer; total cholesterol.

Figure 1.. Highest vs. lowest meta-analysis on the association of total cholesterol level and risk of prostate cancer.

(A) Overall prostate cancer; (B) Higher-grade prostate cancer; (C) Advanced prostate cancer. ¹ For PCPT study (Platz 2009), RR of Gleason sum ≥ 7 was used rather than that of Gleason sum ≥ 8 (RR=2.17, 95%CI: 0.87–5.43). ² For HPFS study (Liu 2022, current study), OR of Gleason sum ≥ 7 was used rather than that of Gleason sum ≥7 (4+3).

Figure 2.. Dose-response meta-analysis on the association of total cholesterol level and risk of prostate cancer using 3-knot restricted cubic spline model.

(A) Overall prostate cancer; (B) Higher-grade prostate cancer; (C) Advanced prostate cancer.