Cholesterol and breast cancer risk: a systematic review and meta-analysis of prospective studies

Abstract

The objective of the present study was to conduct the first systematic review and meta-analysis of prospective studies investigating the associations between total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels and the risk of breast cancer. Relevant studies were identified in PubMed (up to January 2014). Inclusion criteria were original peer-reviewed publications with a prospective design. Random-effects models were used to estimate summary hazard ratios (HR) and 95 % CI. Distinction was made between studies that did or did not exclude cancer cases diagnosed during the first years of follow-up, thereby eliminating potential preclinical bias. Overall, the summary HR for the association between TC and breast cancer risk was 0·97 (95 % CI 0·94, 1·00; dose -response per 1 mmol/l increment, thirteen studies), and that between HDL-C and breast cancer risk was 0·86 (95 % CI 0·69, 1·09; dose -response per 1 mmol/l increment, six studies), with high heterogeneity (I 2 ¼ 67 and 47 %, respectively). For studies that eliminated preclinical bias, an inverse association was observed between the risk of breast cancer and TC (dose -response HR 0·94 (95 % CI 0·89, 0·99), seven studies, I 2 ¼ 78 %; highest v. lowest HR 0·82 (95 % CI 0·66, 1·02), nine studies, I 2 ¼ 81 %) and HDL-C (dose -response HR 0·81 (95 % CI 0·65, 1·02), five studies, I 2 ¼ 30 %; highest v. lowest HR 0·82 (95 % CI 0·69, 0·98), five studies, I 2 ¼ 0 %). There was no association observed between LDL-C and the risk of breast cancer (four studies). The present meta-analysis confirms the evidence of a modest but statistically significant inverse association between TC and more specifically HDL-C and the risk of breast cancer, supported by mechanistic plausibility from experimental studies. Further large prospective studies that adequately control for preclinical bias are needed to confirm the results on the role of cholesterol level and its fractions in the aetiology of breast cancer.Key words: Cholesterol: HDL-cholesterol: Breast cancer: Prospective studies: Meta-analysesBreast cancer is one of the leading causes of death among women in developed countries. The association between deregulated lipid metabolism and the risk of CVD is well established (1) . In contrast, regarding breast cancer, the role of biomarkers of lipid metabolism has been less investigated and remains unclear. This is notably the case for blood cholesterol levels, which represent easily measurable markers that are often assessed in clinical practice. Experimental studies have provided evidence about the possible mechanisms by which cholesterol (especially HDL-cholesterol (HDL-C)) could influence carcinogenesis (2 -4) .Since the 1980s and until very recently (5 -10) , many studies have investigated the relationship between total cholesterol (TC) and the risk of breast cancer (5,7,9 -21) , some providing specific results regarding HDL-C (6 -9,15,22 -27) and fewer investigating LDLcholesterol (LDL-C) (7,9,15,16) , apoA1 and apoB (7,9) . These studies ha...

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