Methylenetetrahydrofolate reductase polymorphisms modify BRCA1-associated breast and ovarian cancer risks.
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.
Jakubowska
Anna
A
Pomeranian Medical University, ul Polabska 4, 70-111, Szczecin, Poland.
Gronwald
Jacek
J
Menkiszak
Janusz
J
Górski
Bohdan
B
Huzarski
Tomasz
T
Byrski
Tomasz
T
Edler
Lutz
L
Lubiński
Jan
J
Scott
Rodney J
RJ
Hamann
Ute
U
D015992:Body Mass Index; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008957:Models, Genetic; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D011044:Poland; D011110:Polymorphism, Genetic; D012306:Risk
D042965:Methylenetetrahydrofolate Reductase (NADPH2)