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Polymorphisms of methylenetetrahydrofolate reductase and methionine synthase genes and bladder cancer risk: a case–control study with meta-analysis

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Abstract

Folate deficiency due to the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) variants leads to carcinogenesis by affecting DNA synthesis, repair, and methylation. We hypothesized that the MTHFR C677T, A1298C, and MS A2756G polymorphisms are associated with risk of bladder cancer. In a case–control study of 239 bladder cancer cases and 250 cancer-free controls, we found that the MTHFR 677TT genotype was statistically significantly associated with an increased risk of bladder cancer compared with the 677CC genotype (OR = 2.06, 95% CI = 1.16–3.64). Furthermore, the TA haplotype was associated with a significantly increased bladder cancer risk (OR = 1.38, 95% CI = 1.05–1.81) than was the most common haplotype, CA (e.g., CA denotes MTHFR 677C -1298A). We also found that the combined genotypes with 4–6 variant (risk) alleles (i.e., MTHFR 677T, 1298A, and MS 2756G alleles) were associated with an increased risk of bladder cancer (OR = 1.62, 95% CI = 1.03–2.53) compared with those with 0–3 variants, and this increased risk was more pronounced among subgroup of older people (OR = 1.71, 95% CI = 1.03–2.83). A meta-analysis of seven studies did not show a significant risk of bladder cancer in the MTHFR polymorphisms. The MTHFR polymorphisms and their haplotypes appear to jointly contribute to risk of bladder cancer.

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Acknowledgments

This study was partly supported by the National Natural Science Foundation of China (30571583 and 30876444), the PhD Programs Foundation of Ministry of Education of China (20060312002), the Natural Science Foundation of Jiangsu Province (BK2006231), the Postdoctoral Science Foundation of China (20060390293), the Postdoctoral Science Foundation of Jiangsu Province (0601049) and “Qinglan Project” Fundation for the Young Academic Leader of Jiangsu Province (2006).

Conflict of interest statement

The authors declare that they have no conflict of interest related to the publication of this manuscript.

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Authors and Affiliations

  1. Department of Molecular and Genetic Toxicology, School of Public Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, China

    Meilin Wang, Haixia Zhu, Miaomiao Wang, Zhizhong Zhang, Shizhi Wang & Zhengdong Zhang

  2. Department of Urology, The Huai-An First Affiliated Hospital, Nanjing Medical University, Huai-An, China

    Guangbo Fu

  3. Department of Urology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China

    Qiang Lu

  4. Department of Epidemiology and Biostatistics, Nanjing Medical University, Nanjing, China

    Zhengdong Zhang

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  1. Meilin Wang
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Correspondence to Zhengdong Zhang.

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M. Wang, H. Zhu and G. Fu contributed equally to this work.

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Wang, M., Zhu, H., Fu, G. et al. Polymorphisms of methylenetetrahydrofolate reductase and methionine synthase genes and bladder cancer risk: a case–control study with meta-analysis. Clin Exp Med 9, 9–19 (2009). https://doi.org/10.1007/s10238-008-0013-1

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