Polymorphisms in methionine synthase, methionine synthase reductase and serine hydroxymethyltransferase, folate and alcohol intake, and colon cancer risk.
OBJECTIVE
We examined associations among folate and alcohol intake, single nucleotide polymorphisms (SNPs) in genes involved in one-carbon metabolism, and colon cancer risk.


METHODS
Colon cancer cases (294 African-Americans and 349 whites) were frequency matched to population controls (437 African-Americans and 611 whites) by age, race and sex from 33 North Carolina counties from 1996 to 2000. Folate and alcohol intakes were collected by dietary interview. Five SNPs were genotyped using DNA from whole blood: SHMT C1420T; MTRR A66G; MTR A2756G, and the previously-reported MTHFR C677T and MTHFR A1298C. Adjusted odds ratios (OR) and 95% CI were calculated using logistic regression.


RESULTS
An inverse association was observed for SHMT TT genotype as compared to CC genotype in whites (OR = 0.6, 95% CI = 0.4, 1.0), but not in African Americans. Inverse associations were observed for high folate intake in individuals carrying 0 or 1 variant allele [OR 0.2 (95% CI 0.06-0.8) for African-Americans; OR 0.2 (95% CI 0.1-0.6) for whites] compared to low folate intake. Modest interactions between these SNPs and alcohol or folate intakes were observed.


CONCLUSIONS
Our results are consistent with other findings and provide needed data on these associations among African-Americans.
Department of Nutrition, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, N.C., USA. ssteck@sc.edu
Susan E
SE
Steck
Temitope
T
Keku
Lesley M
LM
Butler
Joseph
J
Galanko
Beri
B
Massa
Robert C
RC
Millikan
Robert S
RS
Sandler
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D002277:Carcinoma / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D004435:Eating / Q000502:physiology; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005492:Folic Acid / Q000378:metabolism*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D012696:Glycine Hydroxymethyltransferase