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Colorectal adenomas and the C677T MTHFR polymorphism: evidence for gene-environment interaction?
Cancer Epidemiol Biomarkers Prev. 1999 Aug; 8(8):659-68.CE

Abstract

5,10-Methylene-tetrahydrofolate reductase (MTHFR), an enzyme in folate metabolism, may play a role in the etiology of colorectal adenomas via effects on DNA methylation and nucleotide synthesis. We investigated the association between a common polymorphism (C677T, reduced MTHFR activity) and colorectal adenomas within the Minnesota CPRU case-control study. Cases (n = 527) were diagnosed with colonoscopically confirmed adenomas; controls (n = 645) were derived from the same gastroenterology practice and were polyp free at colonoscopy. Dietary intakes were obtained from a self-administered food-frequency questionnaire prior to colonoscopy. Age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals for the MTHFR genotype were 0.9 (0.7-1.2; CT versus CC wild-type) and 0.8 (0.6-1.3; TT versus CC). The associations between dietary intakes of folate, vitamin B12, vitamin B6, or methionine and risk of adenomas showed consistent patterns dependent upon MTHFR genotype. Individuals with the TT genotype and intakes of any of these nutrients in the lowest tertile were at elevated risk for adenomas (about 2-3-fold when compared with TT genotype with high intakes). These trends were more pronounced among individuals over age 60, resulting in a 3-6-fold increase for low intakes of folate, B12, and B6. An increased risk with increasing alcohol consumption was observed only among those with the CC genotype (P-trend = 0.005); among those with the TT genotype, those with moderate alcohol consumption were at lowest risk (P for interaction P = 0.02). In conclusion, nutrients involved in the MTHFR metabolic pathway may modify the relationship between the MTHFR C677T polymorphism and colorectal adenomas. Low intakes of folate, vitamin B12, and vitamin B6 increase risk among those (particularly the elderly) with the MTHFR TT genotype.

Authors+Show Affiliations

Fred Hutchinson Cancer Research Center, Cancer Prevention Research Program, Seattle, Washington 98109-1024, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10744125

Citation

Ulrich, C M., et al. "Colorectal Adenomas and the C677T MTHFR Polymorphism: Evidence for Gene-environment Interaction?" Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 8, no. 8, 1999, pp. 659-68.
Ulrich CM, Kampman E, Bigler J, et al. Colorectal adenomas and the C677T MTHFR polymorphism: evidence for gene-environment interaction? Cancer Epidemiol Biomarkers Prev. 1999;8(8):659-68.
Ulrich, C. M., Kampman, E., Bigler, J., Schwartz, S. M., Chen, C., Bostick, R., Fosdick, L., Beresford, S. A., Yasui, Y., & Potter, J. D. (1999). Colorectal adenomas and the C677T MTHFR polymorphism: evidence for gene-environment interaction? Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 8(8), 659-68.
Ulrich CM, et al. Colorectal Adenomas and the C677T MTHFR Polymorphism: Evidence for Gene-environment Interaction. Cancer Epidemiol Biomarkers Prev. 1999;8(8):659-68. PubMed PMID: 10744125.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Colorectal adenomas and the C677T MTHFR polymorphism: evidence for gene-environment interaction? AU - Ulrich,C M, AU - Kampman,E, AU - Bigler,J, AU - Schwartz,S M, AU - Chen,C, AU - Bostick,R, AU - Fosdick,L, AU - Beresford,S A, AU - Yasui,Y, AU - Potter,J D, PY - 2000/4/1/pubmed PY - 2000/5/20/medline PY - 2000/4/1/entrez SP - 659 EP - 68 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol. Biomarkers Prev. VL - 8 IS - 8 N2 - 5,10-Methylene-tetrahydrofolate reductase (MTHFR), an enzyme in folate metabolism, may play a role in the etiology of colorectal adenomas via effects on DNA methylation and nucleotide synthesis. We investigated the association between a common polymorphism (C677T, reduced MTHFR activity) and colorectal adenomas within the Minnesota CPRU case-control study. Cases (n = 527) were diagnosed with colonoscopically confirmed adenomas; controls (n = 645) were derived from the same gastroenterology practice and were polyp free at colonoscopy. Dietary intakes were obtained from a self-administered food-frequency questionnaire prior to colonoscopy. Age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals for the MTHFR genotype were 0.9 (0.7-1.2; CT versus CC wild-type) and 0.8 (0.6-1.3; TT versus CC). The associations between dietary intakes of folate, vitamin B12, vitamin B6, or methionine and risk of adenomas showed consistent patterns dependent upon MTHFR genotype. Individuals with the TT genotype and intakes of any of these nutrients in the lowest tertile were at elevated risk for adenomas (about 2-3-fold when compared with TT genotype with high intakes). These trends were more pronounced among individuals over age 60, resulting in a 3-6-fold increase for low intakes of folate, B12, and B6. An increased risk with increasing alcohol consumption was observed only among those with the CC genotype (P-trend = 0.005); among those with the TT genotype, those with moderate alcohol consumption were at lowest risk (P for interaction P = 0.02). In conclusion, nutrients involved in the MTHFR metabolic pathway may modify the relationship between the MTHFR C677T polymorphism and colorectal adenomas. Low intakes of folate, vitamin B12, and vitamin B6 increase risk among those (particularly the elderly) with the MTHFR TT genotype. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/10744125/Colorectal_adenomas_and_the_C677T_MTHFR_polymorphism:_evidence_for_gene_environment_interaction L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=10744125 DB - PRIME DP - Unbound Medicine ER -