Methylenetetrahydrofolate reductase polymorphism and susceptibility to breast cancer.
BACKGROUND
A growing body of evidence suggests that variations in the levels of folate may contribute to the development of cancer. A functional polymorphic variant (C-->T substitution at nucleotide 677) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene results in the conversion of an alanine to a valine and may modify the risk of breast and other cancers.


METHODS
We have investigated the possible influence of this MTHFR variant on breast cancer risk in a case-control study of 233 healthy women and 335 women who had breast cancer that occurred under the age of 40 years, bilateral breast cancer or a family history of breast cancer.


RESULTS
A significant excess of the valine genotypes was observed among the cases (odds ratio 1.43, 95% confidence interval 1.02-2.00). The effect was more pronounced among the cases with a breast cancer diagnosis under the age of 40 years, with an odds ratio of 1.66 (95% confidence interval 1.12-2.41). A nonsignificant excess of the valine genotypes was observed among the cases with a family history of breast cancer or bilateral breast cancer.


CONCLUSIONS
The low activity C677T (valine) genotype of MTHFR may increase the risk of early onset breast cancer.
Campbell
Ian G
IG
VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria, 3002, Australia. i.campbell@pmci.unimelb.edu.au
Baxter
Simon W
SW
Eccles
Diana M
DM
Choong
David Y H
DY
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011110:Polymorphism, Genetic
D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)