Abstract
BackgroundThe association between MHTFR Ala222Val polymorphism and breast cancer (BC) risk are inconclusive. To derive a more precise estimation of the relationship, a systematic review and meta-analysis was performed.MethodsA comprehensive search was conducted through researching MEDLINE, EMBASE, PubMed, Web of Science, Chinese Biomedical Literature database (CBM) and China National Knowledge Infrastructure (CNKI) databases before August 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association.ResultsA total of 51 studies including 20,907 cases and 23,905 controls were involved in this meta-analysis. Overall, significant associations were found between MTHFR Ala222Val polymorphism and BC risk when all studies pooled into the meta-analysis (Ala/Ala vs Val/Val: OR=0.870, 95%CI=0.789–0.958,P=0.005; Ala/Val vs Val/Val: OR=0.895, 95%CI=0.821–0.976, P=0.012; dominant model: OR=0.882, 95%CI=0.808–0.963, P=0.005; and recessive model: OR = 0.944, 95%CI=0.898–0.993, P=0.026; Ala allele vs Val allele: OR = 0.935, 95%CI=0.887–0.986, P=0.013). In the subgroup analysis by ethnicity, the same results were found in Asian populations, while no significant associations were found for all comparison models in other Ethnicity populations.ConclusionIn conclusion, our meta-analysis provides the evidence that MTHFR Ala222Val gene polymorphisms contributed to the breast cancer development.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1966146911851976
Highlights
Breast cancer is the most common cancer and the main cause of cancer mortality in women
Significant associations were found between methylenetetrahydrofolate reductase (MTHFR) Ala222Val polymorphism and breast cancer (BC) risk when all studies pooled into the meta-analysis (Ala/Ala vs Val/Val: Odds ratio (OR)=0.870, 95%confidence intervals (CIs)=0.789–0.958,P=0.005; Ala/Val vs Val/Val: OR=0.895, 95%CI=0.821–0.976, P=0.012; dominant model: OR=0.882, 95%CI=0.808–0.963, P=0.005; and recessive model: OR = 0.944, 95%CI=0.898–0.993, P=0.026; Ala allele vs Val allele: OR = 0.935, 95%CI=0.887–0.986, P=0.013)
In the subgroup analysis by ethnicity, the same results were found in Asian populations, while no significant associations were found for all comparison models in other Ethnicity populations
Summary
Breast cancer is the most common cancer and the main cause of cancer mortality in women. Studies suggest that the effect determined by low-penetrance genes, may provide a plausible explanation for BC susceptibility. MTHFR Ala222Val polymorphism has become the most commonly studied one, which has been considered to influence the enzyme activity of MTHFR [4]. The MTHFR 222Val/Val (homozygote) genotype results in 30% enzyme activity in vitro compared with the Ala/Ala wild-type [5]. Numerous epidemiological studies have evaluated the association between the MTHFR Ala222Val polymorphisms and BC risk. The association between MHTFR Ala222Val polymorphism and breast cancer (BC) risk are inconclusive. To derive a more precise estimation of the relationship, a systematic review and meta-analysis was performed
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