Folate metabolism polymorphisms influence risk of colorectal adenoma recurrence.
Folate intake is inversely related to risk of developing colorectal neoplasia. Associations between risk of colorectal neoplasia and polymorphisms in genes coding for enzymes involved in folate metabolism have also been reported, suggesting a relationship between genotype and development of colorectal neoplasia. To further investigate the effects of folate metabolism genotypes on colorectal neoplasia, we genotyped 546 patients participating in a randomized controlled trial of folate supplementation for the prevention of colorectal adenoma recurrence. A significantly reduced risk of recurrence was observed in patients heterozygous for the MTRR A66G polymorphism [relative risk (RR), 0.64; 95% confidence interval (95% CI), 0.46-0.90] or heterozygous for the MTHFR A1298C polymorphism (RR, 0.71; 95% CI, 0.52-0.97). Furthermore, a significant reduction in recurrence risk was seen in MTRR A66G heterozygotes who received folate supplements but not in those who did not receive folate. Patients heterozygous for the MTHFR C677T polymorphism had a nonsignificant risk reduction (RR, 0.92; 95% CI, 0.69-1.23), as did patients with one or two variant alleles for the MTR A2756G polymorphism (RR, 0.82; 95% CI, 0.60-1.12). No influence on recurrence risk was observed for the TSER, TSER 3R G>C, and TS 1494del6 variants. These findings provide additional support for the hypothesis that germ line variants in folate metabolism genes influence the development of colorectal adenomas.
Hubner
Richard A
RA
Institute of Cancer Research, Section of Cancer Genetics, 15 Cotswold Road, Sutton SM2 5NG, United Kingdom. Richard.Hubner@icr.ac.uk
Muir
Kenneth R
KR
Liu
Jo-Fen
JF
Sellick
Gabrielle S
GS
Logan
Richard F A
RF
Grainge
Matthew
M
Armitage
Nicholas
N
Chau
Ian
I
Houlston
Richard S
RS
D000236:Adenoma / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005492:Folic Acid / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology*; D011110:Polymorphism, Genetic; D012306:Risk
D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2)