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

Abstract

Objective: Previous 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 methods: A 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.

Results: A 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.

Conclusion: This meta-analysis demonstrates that MTHFR C677T polymorphism may be a risk factor for breast and ovarian cancer, especially in Asians.

Keywords: C677T; MTHFR; breast cancer; meta-analysis; ovarian cancer; polymorphism.

Figure 1

Flow diagram of literature search.

Figure 2

Forest plot of homozygous comparison (CC vs TT) for breast cancer and/or ovarian cancer (cancer type). Note: Weights are from random effects analysis. Abbreviations: OR, odds ratio; CI, confidence interval; BC, breast cancer; OC, ovarian cancer.

Figure 3

Forest plot of homozygous comparison (CC vs TT) for breast cancer and/or ovarian cancer (ethnicity). Note: Weights are from random effects analysis. Abbreviations: OR, odds ratio; CI, confidence interval.

Figure 4

Funnel plot of homozygous comparison (CC vs TT) for breast cancer and/or ovarian cancer. Abbreviations: OR, odds ratio; SE, standard error.

Figure 5

Funnel plot of homozygous comparison (CC vs TT) for breast cancer. Abbreviations: OR, odds ratio; SE, standard error.

Figure 6

Funnel plot of homozygous comparison (CC vs TT) for ovarian cancer. Abbreviations: OR, odds ratio; SE, standard error.