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Gene polymorphisms involved in folate and methionine metabolism and increased risk of sporadic colorectal adenocarcinoma

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Tumor Biology

Abstract

This pilot study has compared the polymorphic genotype frequencies of methylenetetrahydrofolate reductase (MTHFR A1298C and C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), and thymidylate synthase (TS 2R/3R) in 113 patients with sporadic colorectal adenocarcinoma (SCA) and 188 healthy blood donors, used as matched controls. The aim was to assess the role of these genotypes in the increased risk of SCA among the southeastern Brazilian population. Carriers of genotype MTRR 66GG, or the combined variants MTHFR 1298AC + CC plus 677CT + TT, or MTHFR 677CT + TT plus MTR 2756AG + GG, or MTHFR 1298AC + CC plus 677CT + TT plus MTR 2756AG + GG, or yet, MTHFR 1298AC + CC plus 677CT + TT plus MTRR 66AG + GG, respectively, showed an increased risk of the order of 1.99-, 3.26-, 2.22-, 10.92-, and 14.88-fold of developing SCA when compared with carriers of the other studied polymorphic genotypes, whether in isolation or in combination. In addition, individuals with the MTHFR 677CT + TT or the MTR 2756AG + GG genotypes had a 2.12- and a 1.42-fold increased risks of SCA onset before 50 years of age. African-Brazilians with the MTRR 66GG genotype had a 1.98-fold increased risk of SCA while individuals with the MTR 2756AG + GG and the MTHFR 677CT + TT genotypes showed a 2.11- and a 1.62-fold increased risk of undifferentiated and advanced tumors at diagnosis, respectively. Carriers of genotype MTHFR 1298AC + CC or MTHFR 1298AC + CC plus MTRR 66AG + GG had a 1.42- and a 3.07-fold increased risk of rectal tumor, respectively. Additionally, carriers of MTHFR 677CT + TT or MTHFR 677CT + TT plus TS 2R/3R + 3R/3R had a 1.55- and a 5.39-fold increased risk for colon tumor, respectively, in comparison with carriers of the wild genotypes. These data suggest that all polymorphisms coding for folate and methionine-dependent enzymes, particularly when present in combination with other polymorphisms, have consistent roles in the increased risk of SCA among the southeastern population of Brazil.

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Acknowledgments

We thank Dr. Daniela Benzano for the statistical support and the Fundação de Apoio à Pesquisa do Estado de São Paulo for the research grants.

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Authors and Affiliations

  1. Service of Oncohematology, Department of Clinical Oncology from Hospital Santa Rita (Complexo Hospitalar Santa Casa), Grupo Hospitalar Conceição, Rua Capitão Pedro Werlang, 614, Partenon, Porto Alegre, Rio Grande do Sul, Cep.: 91530110, Brazil

    José Luiz Miranda Guimarães

  2. Department of Surgery, Faculty of the Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil

    Maria de Lurdes Ayrizono & Cláudio Saddy Rodrigues Coy

  3. Clinical Oncology Service, Department of Internal Medicine, Faculty of the Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil

    Carmen Silvia Passos Lima

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  1. José Luiz Miranda Guimarães
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Correspondence to José Luiz Miranda Guimarães.

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Guimarães, J.L.M., Ayrizono, M.d., Coy, C.S.R. et al. Gene polymorphisms involved in folate and methionine metabolism and increased risk of sporadic colorectal adenocarcinoma. Tumor Biol. 32, 853–861 (2011). https://doi.org/10.1007/s13277-011-0185-2

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