Elevated Cholesterol Linked to Aggressive Prostate Cancer

Kashif Shafique, MD

Men with increased cholesterol levels may have an elevated risk of developing high-grade prostate cancer, according to a Scottish research team. However, the data, from a population-based prospective cohort study, also show that elevated cholesterol levels are not associated with a higher overall risk of prostate cancer.

“The potential clinical implications of our findings are that increasing obesity and associated dyslipidemia may have been responsible for the increasing incidence of prostate cancer and that modifying cholesterol may reduce incidence of more aggressive disease,” Kashif Shafique, MD, University of Glasgow, Scotland, and colleagues noted.

In their study, the researchers examined the association between plasma cholesterol level and both overall and grade-specific prostate cancer incidence in 12,926 men enrolled in the Midspan studies between 1970 and 1976 and followed until December 31, 2007. The Midspan studies are a series of prospective epidemiological studies in men and women aged 21 to 75 years that were launched in Scotland in the late 1960s.

Prostate cancer is approximately six times more common in developed countries than in less developed countries, thereby suggesting that modifiable Western lifestyle factors may be an important contributor, Shafique et al observed. While several studies have looked at the relationship between serum cholesterol levels and the incidence of prostate cancer and its associated mortality, the results have been contradictory. Also, the earlier studies did not exclude early events, which introduces the possibility of “reverse causality,” whereby undetected disease modifies cholesterol prior to diagnosis, the authors noted.

Given that age, genetics, and ethnicity are nonmodifiable risk factors, a possible impact of cholesterol on prostate cancer risk may have clinical relevance.

The analysis excluded individuals diagnosed with prostate cancer within 5 years of baseline cholesterol assay in order to decrease the potential for reverse causality.

Overall, 650 men developed prostate cancer in up to 37 years’ follow-up. Baseline plasma cholesterol was positively associated with the risk of high-grade prostate cancer, which referred to a Gleason score ≥8.

Men in the higher cholesterol group (≥6.21 mmol/L) had a significantly increased risk of developing highgrade disease (hazard ratio = 1.75; 95% CI, 1.03-2.97; P = .036) than men with a desirable cholesterol level (<5.1 mmol/L) after controlling for body mass index, smoking, and socioeconomic status.

Shafique et al called for additional research to explain temporal trends in grade-specific prostate cancer and the biological mechanisms that may underlie the link between cholesterol and prostate cancer.

Shafique K, McLoone P, Qureshi K, et al. Cholesterol and the risk of grade-specific prostate cancer incidence: evidence from two large prospective cohort studies with up to 37 years’ follow up. BMC Cancer. 2012;12:25. doi:10.1186/1471-2407-12-25.