Abstract
BackgroundCatechol-O-methyltransferase (COMT) is one of the most important enzymes involved in estrogen metabolism and its functional genetic polymorphisms may be associated with breast cancer (BC) risk. Many epidemiological studies have been conducted to explore the association between the COMT Val158Met polymorphism and breast cancer risk. However, the results remain inconclusive. In order to derive a more precise estimation of this relationship, a large meta-analysis was performed in this study.MethodsSystematic searches of the PubMed, Embase and Cochrane Library were performed. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association.ResultsA total of 56 studies including 34,358 breast cancer cases and 45,429 controls were included. Overall, no significant associations between the COMT Val158Met polymorphism and breast cancer risk were found for LL versus HH, HL versus HH, LL versus HL, recessive model LL versus HL+HH, and dominant model LL+HL versus HH. In subgroup analysis by ethnicity, source of controls, and menopausal status, there was still no significant association detected in any of the genetic models.ConclusionOur meta-analysis results suggest that the COMT Val158Met polymorphism may not contribute to breast cancer susceptibility.Virtual slidesThe virtual slides(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs4806123577708417
Highlights
Breast cancer is one of the most frequently occurring cancer and cancer-related deaths are highly prevalent worldwide, which has become a major public health challenge [1]
Study characteristics According to our search criteria, 61 studies relevant to the role of COMT Val158Met polymorphism on breast cancer (BC) risk were identified
A total of 56 separate comparisons consisting of 34,358 BC patients and 45,429 controls were included in our meta-analysis
Summary
Breast cancer is one of the most frequently occurring cancer and cancer-related deaths are highly prevalent worldwide, which has become a major public health challenge [1]. A G to A transition in the COMT gene results in valine to methionine amino acid change in codon 108/158 in the cytosolic/membrane-bound form of the protein. This amino acid change is believed to result in a 3–4-fold decrease in enzymatic activity [6,7]. It has been hypothesized that the individuals who inherit the low activity COMT-L gene may be at increased risk for breast cancer because of an increased accumulation of the catechol estrogen intermediates [8,9,10,11]. Catechol-O-methyltransferase (COMT) is one of the most important enzymes involved in estrogen metabolism and its functional genetic polymorphisms may be associated with breast cancer (BC) risk. In order to derive a more precise estimation of this relationship, a large meta-analysis was performed in this study
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