<em>MTHFR C677T</em> polymorphism and breast, ovarian cancer risk: a meta-analysis of 19,260 patients and 26,364 controls

Abstract

ObjectivePrevious studies have found that many gene variations can be detected in both breast cancer and ovarian cancer, which is beneficial for the elaboration of the molecular origin of breast and ovarian cancer. Furthermore, many studies have explored the association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with the risk of breast cancer and/or ovarian cancer; however, the results remained inconclusive. Therefore, this study conducted a systematic review and meta-analysis to evaluate the association between MTHFR C677T polymorphism and the risk of breast and ovarian cancer.Materials and methodsA total of 50 studies with 19,260 cases and 26,364 controls including 39 studies for breast cancer and 8 studies for ovarian cancer were identified on searching through PubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang, and Database of Chinese Scientific and Technical Periodicals (VIP). Allele model, dominant model, recessive model, homozygous model, and co-dominant model were applied to evaluate the association of MTHFR C677T polymorphism with breast cancer and/or ovarian cancer risk. Moreover, the odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association between MTHFR C677T polymorphism and breast and ovarian cancer risk.ResultsA significantly increased breast cancer risk was observed in the overall analysis (for C vs T, OR =1.19, CI: 1.12–1.28, P<0.05; for CC vs TT, OR =1.20, CI: 1.10–1.23, P<0.05; for (CT+CC) vs TT, OR =1.19, CI: 1.11–1.27, P<0.05; for CC vs (CT+TT), OR =1.19, CI: 1.79–1.95, P<0.05), while no significantly increased ovarian cancer risk was detected. In the subgroup analysis based on ethnicity, a significant association of breast cancer and/or ovarian cancer risk with MTHFR C677T polymorphism was observed in Asians. Interestingly, there was no significant association between MTHFR C677T polymorphism and ovarian cancer risk in Caucasians, whereas a significantly increased risk of breast cancer was found in Caucasians.ConclusionThis meta-analysis demonstrates that MTHFR C677T polymorphism may be a risk factor for breast and ovarian cancer, especially in Asians.

Association of MTHFR 677C>T Polymorphism with Susceptibility to Ovarian and Cervical Cancers: A Systematic Review and Meta-Analysis

“…Epidemiological studies had identified that Methylene tetrahydrofolate reductase (MTHFR) was a potential genetic marker of different malignancies (Yi et al, 2016;He and Shen, 2017). The human MTHFR gene is located on chromosome 1p36.3, consist of 11 exons and spans 2.2 kb of genomic DNA (Abedinzadeh et al, 2015;Azarpira et al, 2018).…”

“…Over the past decades, a large number of epidemiological studies and meta-analyses have evaluated the association between the MTHFR 677C>T polymorphism and susceptibility to ovarian and cervical cancer (Yi et al, 2016;He and Shen, 2017). However, the results were conflicting and inconclusive, presumably due to small sample size in each published study, various genetic backgrounds and possible selection bias (He and Shen, 2017). Subsequently, a few novel studies have recently been performed to estimate the associations of MTHFR 677C>T polymorphism with risk of ovarian and cervical cancer and provide new evidences that were not included in the previous meta-analyses.…”

Risk factors predisposing to cardia gastric adenocarcinoma: Insights and new perspectives

“…The enzyme methylenetetrahydrofolate reductase (MTHFR) has an important role in the regulation of methionine and homocysteine concentrations in folate metabolism . Individuals with the MTHFR 677TT variant genotype possessed a twofold increased CGA risk (OR = 2.04)…”

The influence of MTHFR C677T polymorphism in chronic lymphocytic leukemia

“…Reports have demonstrated that MTHFR C677T polymorphism is associated with other pathologies . On the other hand, there is no consensus on the effect of this polymorphism in the susceptibility to CLL .…”

“…Moreover, the mutant genotype conditions an enzyme with only 30% enzymatic activity when compared to wild‐type . Thus, the lower enzymatic activity contributes to hypomethylation leading to lower levels of circulating 5‐MTHF and increasing the plasma homocysteine levels . Therefore, the hyperhomocysteine promotes inflammatory processes via oxidative stress, cytokines, and chemokines, which may contribute to the carcinogenesis process .…”