TY - JOUR
T1 - Methylenetetrahydrofolate reductase 677 C→T polymorphism and risk of proximal colon cancer in North Italy
AU - Toffoli, Giuseppe
AU - Gafà, Roberta
AU - Russo, Antonio
AU - Lanza, Giovanni
AU - Dolcetti, Riccardo
AU - Sartor, Franca
AU - Libra, Massimo
AU - Viel, Alessandra
AU - Boiocchi, Mauro
PY - 2003/2/1
Y1 - 2003/2/1
N2 - Purpose: Gene silencing by hypermethylation plays an important role in proximal colon carcinogenesis. Conversely, DNA hypomethylation has been associated with distal colon cancer (CLC). Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5′,10′-methylenetetrahydrofolate to 5′-methyl tetrahydrofolate, which serves as methyl donor in the remethylation of homocysteine to methionine. A common MTHFR 677 C→T polymorphism is characterized by reduced catalytic activity, which affects methionine synthesis and DNA methylation. The aim of the study was to investigate the role of MTHFR 677 C→T gene polymorphism in the tumorigenesis of proximal and distal CLC in a monoinstitutional group of patients in North Italy. Experimental Design: One-hundred thirty four consecutive proximal and 142 consecutive distal CLC patients, and 279 control subjects without cancer were genotyped for MTHFR using PCR-restriction fragment-length polymorphism analysis. Results: The prevalence of the 677 TT genotype was significantly (P = 0.005) lower in patients with proximal tumors (10 of 134, 7%) than in subjects with distal tumors (28 of 142, 20%). Case/control approach indicated that individuals homozygous for the 677 TT allele had a significantly reduced risk (2.8-fold) (adjusted odds ratio, 0.36; 95% confidence intervals, 0.14-0.91) of developing proximal CLC compared with those harboring the wild-type or heterozygous genotype (677 CC or 677 CT). No significant association between CLC risk and TT genotype was observed in patients with distal tumors (odds ratio, 1.01; 95% confidence interval, 0.48-2.14). Conclusions: Our findings support a role for MTHFR 677 TT genotype in reducing proximal CLC risk in North Italy.
AB - Purpose: Gene silencing by hypermethylation plays an important role in proximal colon carcinogenesis. Conversely, DNA hypomethylation has been associated with distal colon cancer (CLC). Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5′,10′-methylenetetrahydrofolate to 5′-methyl tetrahydrofolate, which serves as methyl donor in the remethylation of homocysteine to methionine. A common MTHFR 677 C→T polymorphism is characterized by reduced catalytic activity, which affects methionine synthesis and DNA methylation. The aim of the study was to investigate the role of MTHFR 677 C→T gene polymorphism in the tumorigenesis of proximal and distal CLC in a monoinstitutional group of patients in North Italy. Experimental Design: One-hundred thirty four consecutive proximal and 142 consecutive distal CLC patients, and 279 control subjects without cancer were genotyped for MTHFR using PCR-restriction fragment-length polymorphism analysis. Results: The prevalence of the 677 TT genotype was significantly (P = 0.005) lower in patients with proximal tumors (10 of 134, 7%) than in subjects with distal tumors (28 of 142, 20%). Case/control approach indicated that individuals homozygous for the 677 TT allele had a significantly reduced risk (2.8-fold) (adjusted odds ratio, 0.36; 95% confidence intervals, 0.14-0.91) of developing proximal CLC compared with those harboring the wild-type or heterozygous genotype (677 CC or 677 CT). No significant association between CLC risk and TT genotype was observed in patients with distal tumors (odds ratio, 1.01; 95% confidence interval, 0.48-2.14). Conclusions: Our findings support a role for MTHFR 677 TT genotype in reducing proximal CLC risk in North Italy.
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M3 - Article
C2 - 12576444
AN - SCOPUS:0037312526
VL - 9
SP - 743
EP - 748
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 2
ER -