Effects of methylenetetrahydrofolate reductase single-nucleotide polymorphisms on breast,cervical,ovarian,and endometrial cancer susceptibilities

Background:Recent studies identifying methylenetetrahydrofolate reductase(MTHFR)polymorphisms associated with breast cancer(BC),ovarian cancer(OC),cervical cancer,and endometrial cancer(EC)have reported conflicting results and been underpowered.To clarify the correlation betweenMTHFR mutations and these common female malignancies,we conducted a comprehensive meta-analysis incorporating all eligible publications.Methods:Relevant reports published before January 20,2020,were retrieved from PubMed,Embase,the Cochrane Library,and the China National Knowledge Infrastructure databases.The odds ratio and 95% confidence interval summaries for theMTHFR 677C/T and 1298A/C polymorphisms in BC,OC,cervical cancer,and EC were estimated.Results:A total of 171 studies comprising 56,675 cancer cases and 67,559 controls were included.The results showed a markedly elevated risk of cancer susceptibility related toMTHFR 677C/T based on all genetic models.Similarly,we identified a significant correlation between 1298A/C mutation and cancer risk based on overall comparisons among all models,except the heterozygous model.Moreover,subgroup analysis by cancer type revealed a significantly increased risk of BC associated with 677C/T in the five models and of cervical cancer associated with 1298A/C in some models.Based on ethnicity,significant associations were observed between Asian,African,and mixed populations for 677C/T and the Asian population for 1298A/C.With regard to the sample type used for analysis,we detected a positive association between using blood as the DNA source and cancer risk for 677C/T in all genetic models and for 1298A/C in some genetic models.Further stratification of the results revealed that a notably increased risk was associated with the use of polymerase chain reaction-restriction fragment-length polymorphism or TaqMan as the genotyping method,as well as with the use of population-or hospital-based groups as the controls for 677C/T and 1298A/C,respectively.Conclusion:This meta-analysis suggests thatMTHFR 677C/T and 1298A/C polymorphisms correlate with the risk of common gynecological cancers,with these findings potentially applicable for overall comparisons of related data.