Alcohol consumption and genetic variation in methylenetetrahydrofolate reductase and 5-methyltetrahydrofolate-homocysteine methyltransferase in relation to breast cancer risk.
It has been hypothesized that effects of alcohol consumption on one-carbon metabolism may explain, in part, the association of alcohol consumption with breast cancer risk. The methylenetetrahydrofolate reductase (MTHFR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) genes express key enzymes in this pathway. We investigated the association of polymorphisms in MTHFR (rs1801133 and rs1801131) and MTR (rs1805087) with breast cancer risk and their interaction with alcohol consumption in a case-control study--the Western New York Exposures and Breast Cancer study. Cases (n = 1,063) were women with primary, incident breast cancer and controls (n = 1,890) were frequency matched to cases on age and race. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression. We found no association of MTHFR or MTR genotype with risk of breast cancer. In the original case-control study, there was a nonsignificant increased odds of breast cancer among women with higher lifetime drinking. In the current study, there was no evidence of an interaction of genotype and alcohol in premenopausal women. However, among postmenopausal women, there was an increase in breast cancer risk for women who were homozygote TT for MTHFR C677T and had high lifetime alcohol intake (>or=1,161.84 oz; OR, 1.92; 95% CI, 1.13-3.28) and for those who had a high number of drinks per drinking day (>1.91 drinks/day; OR, 1.80; 95% CI, 1.03-3.28) compared with nondrinkers who were homozygote CC. Our findings indicate that among postmenopausal women, increased breast cancer risk with alcohol consumption may be as a result of effects on one-carbon metabolism.
Platek
Mary E
ME
Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY, USA. mary.platek@roswellpark.org
Shields
Peter G
PG
Marian
Catalin
C
McCann
Susan E
SE
Bonner
Matthew R
MR
Nie
Jing
J
Ambrosone
Christine B
CB
Millen
Amy E
AE
Ochs-Balcom
Heather M
HM
Quick
Sylvia K
SK
Trevisan
Maurizio
M
Russell
Marcia
M
Nochajski
Thomas H
TH
Edge
Stephen B
SB
Freudenheim
Jo L
JL
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
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