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

Institute of Health & Wellbeing, Public Health, University of Glasgow, 1 Lilybank Gardens, Glasgow G12 8RZ, UK.
BMC Cancer (Impact Factor: 3.36). 01/2012; 12(1):25. DOI: 10.1186/1471-2407-12-25
Source: PubMed


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.
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.
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.
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.

  • Source
    • "Statins lower cholesterol levels by inhibiting a critical enzyme for cholesterol synthesis, HMGCoA reductase (HMGCR), which is upregulated in CaP and breast cancer tissue [85]. The role of HMGCR in cholesterol synthesis, and a precursor to steroid hormone synthesis, is likely to be an important link in the association between statin use and a lower rate of prostate cancer recurrence [26, 86, 87]. Indeed, it has been shown that statin use inversely correlated with the risk and progression of prostate cancer [88, 89]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity and type 2 diabetes are recognised risk factors for the development of some cancers and, increasingly, predict more aggressive disease, treatment failure, and cancer-specific mortality. Many factors may contribute to this clinical observation. Hyperinsulinaemia, dyslipidaemia, hypoxia, ER stress, and inflammation associated with expanded adipose tissue are thought to be among the main culprits driving malignant growth and cancer advancement. This observation has led to the proposal of the potential utility of "old players" for the treatment of type 2 diabetes and metabolic syndrome as new cancer adjuvant therapeutics. Androgen-regulated pathways drive proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen deprivation therapy (ADT) exploits this dependence to systemically treat advanced prostate cancer resulting in anticancer response and improvement of cancer symptoms. However, the initial therapeutic response from ADT eventually progresses to castrate resistant prostate cancer (CRPC) which is currently incurable. ADT rapidly induces hyperinsulinaemia which is associated with more rapid treatment failure. We discuss current observations of cancer in the context of obesity, diabetes, and insulin-lowering medication. We provide an update on current treatments for advanced prostate cancer and discuss whether metabolic dysfunction, developed during ADT, provides a unique therapeutic window for rapid translation of insulin-sensitising medication as combination therapy with antiandrogen targeting agents for the management of advanced prostate cancer.
    Full-text · Article · Mar 2013 · International Journal of Cell Biology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Numerous epidemiologic studies have implicated abdominal obesity as a major risk factor for insulin resistance, type 2 diabetes mellitus, cardiovascular disease, stroke, metabolic syndrome and its further expression, i.e., nonalcoholic fatty liver disease and death. Using novel models of visceral obesity, several studies have demonstrated that the relationship between visceral fat and longevity is causal, while the accrual of subcutaneous fat does not appear to play an important role in the etiology of disease risk. The need of reducing the visceral fat to improve survival, mainly taking into account the strict link between nonalcoholic fatty liver disease and the coronary artery disease is discussed.
    No preview · Article · Jun 2012 · Hepatology International
  • [Show abstract] [Hide abstract]
    ABSTRACT: Some recent studies have suggested that higher total cholesterol levels are positively associated with risk of aggressive prostate cancer. However, evidence about this association is limited and few studies examined cholesterol subfractions. We therefore examined associations of total, LDL, and HDL cholesterol concentrations with subsequent risk of aggressive prostate cancer within the Cancer Prevention Study II Nutrition Cohort. A total of 14,241 men with no history of cancer provided a blood sample between 1998 and 2001. During follow-up through 2007, 236 of these men were diagnosed with aggressive prostate cancer (AJCC stage ≥ III or Gleason score ≥ 7 (4 + 3)). Plasma total, LDL, and HDL cholesterol concentrations were measured in these 236 cases and 236 age and race-matched controls. Multivariable-adjusted odds ratios (OR) and 95 % confidence intervals (CI) were estimated using conditional logistic regression, adjusting for use of cholesterol-lowering drugs, history of heart attack, and physical activity. Neither total, LDL, nor HDL cholesterol concentrations were associated with risk of aggressive prostate cancer. OR's for a 1 standard deviation (SD) difference were 0.93 (95 % CI 0.76-1.14) for total cholesterol (SD = 33.7 mg/dl), 0.94 (95 % CI 0.77-1.15) for LDL cholesterol (SD = 30.3 mg/dl), and 0.97 (95 % CI 0.82-1.16) for HDL cholesterol (SD = 12.5 mg/dl). Results were similar in analyses excluding the first 2 years of follow-up or users of cholesterol-lowering drugs. These results do not support an association between total cholesterol or its subfractions and risk of aggressive prostate cancer.
    No preview · Article · Jun 2012 · Cancer Causes and Control
Show more