COMT Val158Met polymorphism and breast cancer risk: evidence from 26 case-control studies.

The Catechol-O-methyltransferase (COMT) plays an important role in the development of breast cancer. Many previous epidemiologic studies explored the association of COMT Val158Met polymorphism with breast cancer susceptibility. However, the results were inconsistent. We therefore performed a meta-analysis of 26 published studies including 16,693 breast cancer patients and 18,261 healthy controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association of the COMT Val158Met polymorphism with breast cancer risk. No significant association was found in all genetic models in overall, Asian, European populations. After the studies whose genotype frequencies in the controls did not fulfill Hardy-Weinberg equilibrium were excluded, we found a borderline significant decreased breast cancer risk among Europeans (for the recessive model LL versus HH/HL: OR = 0.90, 95% CI = 0.90-1.00, P (heterogeneity) = 0.33). There was no between-study heterogeneity. In conclusion, COMT Val158Met polymorphism may be a low-penetrant risk factor for breast cancer development in European population.