Abstract
We previously reported (J. Chen et al., Cancer Res., 56:4862–4864, 1996; J. Ma et al., Cancer Res., 57: 1098–1102, 1997) that a 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism (677C→T, ala→val) was associated with lower risk of colorectal cancer. In this study, we examined the relationship of a polymorphism (2756A→G, asp→gly) in the gene (MTR) for methionine synthase, another important enzyme in the same folate/methionine/homocyst(e)ine metabolic pathway, with risk of colorectal cancer among 356 cases and 476 cancer-free controls. The frequency of the homozygous variant genotype (gly/gly) was slightly lower among cases (3%) than controls (5%). The odds ratio for the gly/gly genotype was 0.59 [95% confidence interval (CI), 0.27–1.27] compared with those with the homozygous wild type (asp/asp). There were no significant differences in plasma levels of folate, vitamin B12, and homocyst(e)ine (tHcy) among the MTR genotypes, in contrast to the MTHFR polymorphism. However, similar to the interaction observed for the MTHFR polymorphism among men who consumed less than 1 alcoholic drink/day, those with the gly/gly genotype had a lower risk of colorectal cancer with an odds ratio of 0.27 (95% CI, 0.09–0.81) compared with those with the asp/asp genotype. The possible association of the MTR polymorphism with lower risk of colorectal cancer especially among those with low alcohol consumption, in the same direction as for the MTHFR polymorphism, is intriguing. However, our study had limited statistical power because of the low frequency of the MTR variant genotype, which is reflected in the wide CIs. Hence, these findings need to be confirmed in larger populations.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 Supported by research Grants CA 42182 and CA 40360 from NIH and the Medical Research Council of Canada.
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↵2 To whom requests for reprints should be addressed, at Department of Medicine, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115. Phone: (617) 525-2708; Fax: (617) 525-4597.
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↵3 Present address: 1415 West Camino Real, Boca Raton, FL 33486.
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↵4 The abbreviations used are: SAM, S-adenosylmethionine; MTHFR, 5,10-methylenetetrahydrofolate reductase; tHcy, homocyst(e)ine; OR, odds ratio; CI, confidence interval; PHS, Physician’s Health Study; HPFS, Health Professional Follow-up Study.
- Accepted June 17, 1999.
- Received December 9, 1998.
- Revision received May 19, 1999.