Methylenetetrahydrofolate reductase polymorphisms modify <Emphasis Type="Italic">BRCA1</Emphasis>-associated breast and ovarian cancer risks |
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Authors: | Anna Jakubowska Jacek Gronwald Janusz Menkiszak Bohdan Górski Tomasz Huzarski Tomasz Byrski Lutz Edler Jan Lubiński Rodney J Scott Ute Hamann |
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Institution: | (1) Pomeranian Medical University, ul. Polabska 4, 70-111 Szczecin, Poland;(2) Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center, Im NeuenheimerFeld 580, 69120 Heidelberg, Germany;(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;(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;(5) Central Unit Biostatistics, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany |
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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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Keywords: | BRCA1 carriers Hereditary breast/ovarian cancer MTHFR polymorphisms Polish population Risk modifier |
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