Folate and breast cancer: the role of polymorphisms in methylenetetrahydrofolate reductase (MTHFR).
Evidence is growing that low folate status may be a factor in the aetiology of several cancers, including breast cancer. The methylenetetrahydrofolate reductase gene (MTHFR), which has a key role in folate metabolism, is polymorphic. We report a case-control study of two functional polymorphisms in MTHFR, dietary folate intake and breast cancer. Sixty-two cases with invasive breast cancer and sixty-six general practice controls participated. Women reporting the highest dietary folate intake had non-significantly reduced breast cancer risk (odds ratio (OR) = 0.49, 95% confidence interval (CI) 0.20-1.20). Risk was significantly lower for the 1298CC genotype compared to AA (OR = 0.24, 95% CI 0.06-0.97). Relative to compound wild-type subjects, compound heterozygotes had moderately reduced risk (OR = 0.47, 95% CI 0.11-1.92) and homozygote variants (677TT and/or 1298CC) greater reduced risk (OR = 0.26, 95% CI 0.07-0.96); the trend was statistically significant. Patterns in risk with regard to genotype and folate combinations are broadly similar those reported for colorectal neoplasia. The roles of MTHFR and folate in breast cancer aetiology are likely to be complex.
Sharp
L
L
Epidemiology Group, Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill House Annex, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK. l.sharp@abdn.ac.uk
Little
J
J
Schofield
A C
AC
Pavlidou
E
E
Cotton
S C
SC
Miedzybrodzka
Z
Z
Baird
J O C
JO
Haites
N E
NE
Heys
S D
SD
Grubb
D A
DA
D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D016022:Case-Control Studies; D004032:Diet; D005260:Female; D005492:Folic Acid / Q000494:pharmacology; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D016017:Odds Ratio; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk
D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)