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T Polymorphism and Distal Colorectal Adenoma Risk1
Department of Preventive Medicine, University of Southern California, Los Angeles, California 90089-9181 [A. J. L., K. D. S., C. M. E., A. D., R. W. H.], and Divisions of Gastroenterology, Bellflower [E. R. L.], and Sunset [H. D. F.], Kaiser Permanente Medical Centers, Los Angeles, California 90027
A common polymorphism in the methylenetetrahydrofolate
reductase (MTHFR) gene, where a cytosine at
nucleotide 677 is replaced by a thymine (677C
T), is
associated with enzyme thermolability and a reduction in the conversion
of 5,10-methyltetrahydrofolate (5,10-MTHF) into
5-methyltetrahydrofolate. We assessed the association between
homozygosity for the MTHFR 677CT genotype
(TT) and colorectal adenoma risk in a large
sigmoidoscopy-based case-control study of members of a prepaid health
plan in Los Angeles. MTHFR genotype was determined for
471 cases and 510 age-, sex-, clinic-, and sigmoidoscopy-date-matched
controls. Information on RBC and plasma folate levels were analyzed for
331 cases and 350 controls. When compared with the presence of at least
one wild-type allele (CT/CC), the odds ratio (OR) for
the TT genotype was 1.19 [95% confidence interval
(CI), 0.77–1.76] after adjusting for race and the matching factors.
Compared with those in the lowest quartiles of RBC and plasma folate
and a wild-type allele, adenoma risk was increased for
TT homozygotes in the lowest folate quartiles (genotype:
OR, 2.04 and 95% CI, 0.6–7.0; OR, 1.84 and 95% CI, 0.6–7.0 for RBCs
and plasma folate, respectively) and decreased in TT
homozygotes in the highest quartiles (genotype: OR, 0.82 and 95% CI,
0.32–2.10; OR, 0.65 and 95% CI, 0.22–1.95, respectively). There was
also a significant interaction between TT genotype and
the increased adenoma risk associated with alcohol. These data are
consistent with an interaction between MTHFR genotype
and folate availability.
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