Nonsynonymous polymorphisms in genes in the one-carbon metabolism pathway and associations with colorectal cancer.

Nonsynonymous polymorphisms in genes in the one-carbon metabolism pathway and associations with colorectal cancer. Research Abstract Details 

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Nonsynonymous polymorphisms in genes in the one-carbon metabolism pathway and associations with colorectal cancer. Abstract Text:

Anita Koushik,Peter Kraft,Charles S Fuchs,Susan E Hankinson,Walter C Willett,Edward L Giovannucci,David J Hunter,

The Ala(222)Val single nucleotide polymorphism (SNP) in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in one-carbon metabolism, has been associated with colorectal cancer risk. Many enzymes are involved in one-carbon metabolism, and SNPs in the corresponding genes may play a role in colorectal carcinogenesis. We examined 24 nonsynonymous SNPs in 13 genes involved in the one-carbon metabolism pathway in relation to the risk of colorectal cancer in a case-control study nested in the Nurses' Health Study and the Health Professionals Follow-up Study cohorts. Among 376 men and women with colorectal cancer and 849 controls, a reduced risk of colorectal cancer was observed for Val/Val versus Ala carriers of MTHFR Ala(222)Val [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.43-1.00]. An increased risk was suggested for the variant carrier genotypes versus homozygous wild-type for betaine hydroxymethyltransferase Arg(239)Gln (OR, 1.40; 95% CI, 1.07-1.83) and two linked SNPs in methionine synthase reductase, Ser(284)Thr (OR, 1.85; 95% CI, 1.05-3.27) and Arg(415)Cys (OR, 2.03; 95% CI, 1.15-3.56). The other SNPs were not associated with colorectal cancer risk. Also, none of the SNPs were associated with risk in subgroups of dietary methyl status or were jointly associated with colorectal cancer risk in combination with another SNP, except possibly SNPs in methionine synthase and transcobalamin II. However, these analyses of gene-diet interactions were limited in statistical power. Our results corroborate previous findings for MTHFR Ala(222)Val and suggest that other genes involved in one-carbon metabolism, particularly those that affect DNA methylation, may be associated with colorectal cancer risk.

Nonsynonymous polymorphisms in genes in the one-carbon metabolism pathway and associations with colorectal cancer. Publishing Authors By Initials

A Koushik,P Kraft,CS Fuchs,SE Hankinson,WC Willett,EL Giovannucci,DJ Hunter,

For similar investigative techniques: epidemiologic methods: statistics as topic: probability: risk: risk factors research abstracts see: investigative techniques: epidemiologic methods: statistics as topic: probability: risk: risk factors research

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Nonsynonymous polymorphisms in genes in the one-carbon metabolism pathway and associations with colorectal cancer. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cancer epidemiology, biomarkers & prevention : a p

VOLUME: 15

Page Numbers: 2408-17

Journal Abbreviation: Cancer Epidemiol. Biomarkers P

ISSN: 1055-9965

DAY: 3

MONTH: Dec

YEAR: 2006

Nonsynonymous polymorphisms in genes in the one-carbon metabolism pathway and associations with colorectal cancer. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9200608

Nonsynonymous polymorphisms in genes in the one-carbon metabolism pathway and associations with colorectal cancer. Keywords Mesh Terms:

KEYWORDS: Risk Factors

MESH TERMS: metabolism

Chemical & Substance for Abstract: Nonsynonymous polymorphisms in genes in the one-carbon metabolism pathway and associations with colorectal cancer. Information

Substance Name: Methylenetetrahydrofolate Reductase (NAD

Registry Number: EC 1.5.1.20

Grant and Affiliation Information for Nonsynonymous polymorphisms in genes in the one-carbon metabolism pathway and associations with colorectal cancer.

AFFILIATION: Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.

Country: United States

AGENCY: United States NCI

GRANT: U54-CA100971

ACRONYM: CA

MEDLINETA: Cancer Epidemiol Biomarkers Pr

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