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Methylenetetrahydrofolate reductase polymorphisms modify BRCA1-associated breast and ovarian cancer risks

  • Epidemiology
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Abstract

Methylenetetrahydrofolate reductase (MTHFR), a key regulatory enzyme in the metabolism of folate, is suspected to play a role in the etiology of cancer, via its effects on DNA methylation and nucleotide synthesis. In this study we have investigated the effect of two functional polymorphisms of the MTHFR gene, MTHFR_677_C > T and MTHFR_1298_A > C, on breast and ovarian cancer risk in Polish BRCA1 mutation carriers. The study included 319 breast cancer cases, 146 ovarian cancer cases and 290 controls unaffected by breast and ovarian cancer, in situ breast cancer or any other kind of cancer. Genotyping analysis was performed using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Odds ratios (OR) were calculated using univariate and multivariate logistic regression taking into account a series of confounding variables that potentially could have biased any association. The results revealed that the MTHFR_677_C > T change was associated with an increased risk of breast and ovarian cancer. The MTHFR_1298_A > C polymorphism was only associated with a decrease in breast cancer risk. Together, it appears that functional polymorphisms in the MTHFR gene modify the risk of breast and may potentially alter the risk of ovarian cancer in women with an inherited predisposition.

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Acknowledgments

We thank Antje Seidel-Renkert and Michael Gilbert for expert technical assistance and Renate Rausch for her help in the statistical analysis with SAS. This work was supported by the Deutsches Krebsforschungszentrum, Heidelberg. Anna Jakubowska is a guest researcher from the Pomeranian Medical University, Szczecin, Poland supported by a fellowship from the DKFZ. Anna Jakubowska and Jacek Gronwald were supported by a Yamagiwa-Yoshida Memorial UICC International Cancer Study Grant.

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Authors and Affiliations

  1. Pomeranian Medical University, ul. Polabska 4, 70-111, Szczecin, Poland

    Anna Jakubowska, Jacek Gronwald, Janusz Menkiszak, Bohdan Górski, Tomasz Huzarski, Tomasz Byrski & Jan Lubiński

  2. Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center, Im NeuenheimerFeld 580, 69120, Heidelberg, Germany

    Anna Jakubowska & Ute Hamann

  3. Discipline of Medical Genetics, School of Biomedical Sciences, University of Newcastle and the Hunter Medical Research Institute, Lookout Road, New Lambton, 2305, NSW, Australia

    Rodney J. Scott

  4. Chair and Department of Surgical Gynecology and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, ul. Powstancow Wlkp. 72, 70-111, Szczecin, Poland

    Janusz Menkiszak

  5. Central Unit Biostatistics, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Lutz Edler

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  1. Anna Jakubowska
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  2. Jacek Gronwald
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Correspondence to Ute Hamann.

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Jakubowska, A., Gronwald, J., Menkiszak, J. et al. Methylenetetrahydrofolate reductase polymorphisms modify BRCA1-associated breast and ovarian cancer risks. Breast Cancer Res Treat 104, 299–308 (2007). https://doi.org/10.1007/s10549-006-9417-3

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