Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 104, Issue 3, Pages 299-308Publisher
SPRINGER
DOI: 10.1007/s10549-006-9417-3
Keywords
bRCA1 carriers; hereditary breast/ovarian cancer; MTHFR polymorphisms; Polish population; risk modifier
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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 PolishBRCA1 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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