more evidence of a folate link to breast cancer

[Lani]

More evidence for folate link to breast cancer

MedWire News: Women with the 677TT polymorphism of the Methylenetetrahydrofolate reductase (MTHFR) gene have a 2.4-fold increased risk for breast cancer compared with women with other genotypes, report Italian researchers.

The study further supports evidence previously reported by MedWire News of a role for the folate metabolic pathway in breast cancer pathogenesis.

MTHFR is a key enzyme in the folate pathway and catalyses the conversion of 5,10-methylene-THF to 5-methyl-THF, the latter being the predominant form of folate in blood plasma, explain Andrea Decensi (Ospedali Galliera, Genoa).

They add that individuals with the MTHFR 677 TT genotype have been shown to have only 30% of the in vitro MTHFR enzyme activity associated with the wild type allele, whereas those with the heterozygous CT genotype have been found to have 60% of the wild-type MTHFR enzyme activity.

Some researchers have suggested that reduced activity of these polymorphisms influences the general balance between DNA synthesis, repair, and methylation processes.

The MTHFR 677 TT genotype has also been linked to other cancers including colorectal, gastric, endometrial, lung, and acute leukemia.

In the present study, the researchers obtained DNA samples from 46 women with breast cancer and 80 age-matched controls and genotyped polymorphisms in the MTHFR gene at nucleotide 677.

Among women with breast cancer, the MTHFR genotype frequencies for CC, CT, TT were 30%, 44%, and 26%, respectively. Meanwhile the respective genotype frequencies in controls were 35%, 51%, and 14%.

As reported in the journal Breast Cancer Research and Treatment, there was a higher frequency of the MTHFR 677 TT variant in women with breast cancer (n=12/46) compared with controls (n=11/80).

Decensi et al stress the potential importance of gene-environment interactions in modifying any association between the folate pathway and breast cancer.

Specifically, studies have recently shown that the 677TT polymorphism may interact with endogenous estrogen exposure and dietary intake of folate to modify breast cancer risk, say the researchers.

"There is some evidence that high folate intake may counterbalance the effect of this SNP in increasing breast cancer risk," they add.

"Further studies, taking into account other risk factors for breast cancer, dietary folate intake, and plasma folate levels, are necessary to better understand the role of MTHFR 677 SNP in breast cancer risk," Decensi et al conclude.



Breast Cancer Res Treat 2007; 106: 263-271

http://www.springerlink.com/content/...b71eb05fc&pi=4