TY - JOUR
T1 - Genetic variability in the MTHFR gene and colorectal cancer risk using the colorectal cancer family registry
AU - Levine, A. Joan
AU - Figueiredo, Jane C.
AU - Lee, Won
AU - Poynter, Jenny N.
AU - Conti, David
AU - Duggan, David J.
AU - Campbell, Peter T.
AU - Newcomb, Polly
AU - Martinez, Maria Elena
AU - Hopper, John L.
AU - Le Marchand, Loic
AU - Baron, John A.
AU - Limburg, Paul J.
AU - Ulrich, Cornelia M.
AU - Haile, Robert W.
PY - 2010/1
Y1 - 2010/1
N2 - Background: The MTHFR C677T TT genotype is associated with a 15% to 18% reduction in colorectal cancer risk, but it is not clear if other variants of the gene are associated with colorectal cancer risk. Methods: We used a tagSNP approach to comprehensively evaluate associations between variation in the MTHFR gene and colorectal cancer risk using a large family-based case-control study of 1,750 populationbased and 245 clinic-based families from the Colon Cancer Family Registry. We assessed 22 TagSNPs, selected based on pairwise r 2 >95%, using the Haploview Tagger and genotyped the TagSNPs on the Illumina GoldenGate or Sequenom platforms. The association between single nucleotide polymorphisms and colorectal cancer was assessed using log-additive, codominant, and recessive models. Results: From studying the population-based families, the C677T (rs1801133) and A1298C (rs1801131) polymorphisms were associated with a decreased colorectal cancer risk overall [odds ratio (OR), 0.81; 95% confidence interval (95% CI), 0.63-1.04; and OR, 0.82; 95% CI, 0.64-1.07, respectively]. The 677 TT genotype was associated with a decreased risk of microsatellite-stable/microsatellite-low tumors (OR, 0.69; 95% CI, 0.49-0.97) and an increased risk of microsatellite-high tumors (OR, 2.22; 95% CI, 0.91-5.43; P interaction = 0.01), as well as an increased risk of proximal cancers and a decreased risk of distal and rectal cancers (P interaction = 0.02). No other single nucleotide polymorphism was associated with risk overall or within subgroups. Conclusion: The 677 TT and 1298 CC genotypes may each be associated with a decrease in colorectal cancer risk. We observed little evidence of additional genetic variability in the MTHFR gene relevant to colorectal cancer risk.
AB - Background: The MTHFR C677T TT genotype is associated with a 15% to 18% reduction in colorectal cancer risk, but it is not clear if other variants of the gene are associated with colorectal cancer risk. Methods: We used a tagSNP approach to comprehensively evaluate associations between variation in the MTHFR gene and colorectal cancer risk using a large family-based case-control study of 1,750 populationbased and 245 clinic-based families from the Colon Cancer Family Registry. We assessed 22 TagSNPs, selected based on pairwise r 2 >95%, using the Haploview Tagger and genotyped the TagSNPs on the Illumina GoldenGate or Sequenom platforms. The association between single nucleotide polymorphisms and colorectal cancer was assessed using log-additive, codominant, and recessive models. Results: From studying the population-based families, the C677T (rs1801133) and A1298C (rs1801131) polymorphisms were associated with a decreased colorectal cancer risk overall [odds ratio (OR), 0.81; 95% confidence interval (95% CI), 0.63-1.04; and OR, 0.82; 95% CI, 0.64-1.07, respectively]. The 677 TT genotype was associated with a decreased risk of microsatellite-stable/microsatellite-low tumors (OR, 0.69; 95% CI, 0.49-0.97) and an increased risk of microsatellite-high tumors (OR, 2.22; 95% CI, 0.91-5.43; P interaction = 0.01), as well as an increased risk of proximal cancers and a decreased risk of distal and rectal cancers (P interaction = 0.02). No other single nucleotide polymorphism was associated with risk overall or within subgroups. Conclusion: The 677 TT and 1298 CC genotypes may each be associated with a decrease in colorectal cancer risk. We observed little evidence of additional genetic variability in the MTHFR gene relevant to colorectal cancer risk.
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U2 - 10.1158/1055-9965.EPI-09-0727
DO - 10.1158/1055-9965.EPI-09-0727
M3 - Article
C2 - 20056627
AN - SCOPUS:74549141702
SN - 1055-9965
VL - 19
SP - 89
EP - 100
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 1
ER -