Molecular Biology Reports

, Volume 41, Issue 9, pp 5775–5785 | Cite as

A meta-analysis of genotypes and haplotypes of methylenetetrahydrofolate reductase gene polymorphisms in breast cancer

  • Shanliang Zhong
  • Zhiyuan Chen
  • Xinnian Yu
  • Wenjing Li
  • Jinhai Tang
  • Jianhua Zhao


The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been extensively explored, but their results are conflicting rather than conclusive. To derive a more precise estimation, we carried out not only an updated meta-analysis but also a combined analysis based on all the available studies estimating the association between MTHFR C677T and/or A1298C and breast cancer risk. With respect to C677T polymorphism, the results suggested that 677T allele was associated with significantly elevated breast cancer risk in overall analysis (T vs. C: OR 1.073, 95 % CI 1.028–1.120; TT vs. CC: OR 1.177, 95 % CI 1.072–1.293; TT vs. CC + CT: OR 1.175, 95 % CI 1.073–1.288); Stratifying by ethnicity, significantly increased risk was only found in East Asians (T vs. C: OR 1.150, 95 % CI 1.039–1.273; TT vs. CC: OR 1.441, 95 % CI 1.145–1.814; TT vs. CC + CT: OR 1.413, 95 % CI 1.148–1.739); When stratified by menopausal status, statistically significant association was found for postmenopausal women (CT + TT vs. CC: OR 1.092, 95 % CI 1.011–1.179). In regard to A1298C polymorphism, no significant associations were found between the polymorphism and breast cancer risk. With respect to MTHFR haplotypes, significantly elevated breast cancer risk was associated with 677T-1298C for overall result (OR 1.498, 95 % CI 1.143–1.962) and for Caucasians (OR 2.088, 95 % CI 1.277–3.416) when compared with 677C-1298A; Haplotype 677C-1298C might provide higher protection than 677C-1298A in East Asians (OR 0.840, 95 % CI 0.742–0.949). The combined genotypes for C677T and A1298C produced a significant OR for the 677TT/1298AC relative to 677CC/1298AA in overall population (OR 2.047, 95 % CI 1.275–3.288); When stratified by ethnicity, significant ORs were only found for East Asians (677CC/1298CC vs. 677CC/1298AA: OR 0.686, 95 % CI 0.478–0.985; 677TT/1298AC vs. 677CC/1298AA: OR 2.181, 95 % CI 1.179–4.035). The findings suggest that the MTHFR C677T polymorphism but not A1298C, and some variants on their combined genotypes or haplotypes may be involved with the development of breast cancer.


Breast cancer Meta-analysis MTHFR Polymorphism Haplotype Susceptibility 



This study was supported by the National Natural Science Foundation of China (81272470).

Supplementary material

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Supplementary material 1 (XLS 24 kb)
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Supplementary material 2 (XLS 21 kb)
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Supplementary material 3 (XLS 21 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Shanliang Zhong
    • 1
  • Zhiyuan Chen
    • 2
  • Xinnian Yu
    • 3
  • Wenjing Li
    • 4
  • Jinhai Tang
    • 5
  • Jianhua Zhao
    • 1
  1. 1.Center of Clinical Laboratory ScienceJiangsu Cancer Hospital Affiliated to Nanjing Medical UniversityNanjingChina
  2. 2.Department of General SurgeryThe Affiliated Hospital of Xuzhou Medical CollegeXuzhouChina
  3. 3.Department of Hematology (Key Department of Jiangsu Medicine)Zhongda Hospital, Medical School, Southeast UniversityNanjingChina
  4. 4.Department of Clinical LaboratorySuzhou Municipal Hospital (Headquarters)SuzhouChina
  5. 5.Department of General SurgeryJiangsu Cancer Hospital Affiliated to Nanjing Medical UniversityNanjingChina

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