Journal
AMERICAN JOURNAL OF EPIDEMIOLOGY
Volume 160, Issue 9, Pages 842-852Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/aje/kwh298
Keywords
arylamine N-acetyltransferase; colorectal neoplasms; cytochrome P-450CYP1A1; GSTM1 protein; smoking; tobacco
Categories
Funding
- NCI NIH HHS [R01 CA061757, R01 CA061757-09, R01 CA048998-10, CA48998, R01 CA085846, R01 CA048998, R01 CA085846-05, N01-PC-67000] Funding Source: Medline
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Cytochrome P-450 (CYP) is involved in the activation and metabolism of polycyclic aromatic hydrocarbons in tobacco products. The authors evaluated the association of two polymorphisms in the CYP1A1 gene-the noncoding Msp I polymorphism in the 3'-untranslated region and the Ile462Val polymorphism in exon 7-with colon and rectal cancer. The authors used data from two incident case-control studies of colon cancer (1,026 cases and 1,185 controls) and rectal cancer (820 cases and 1,036 controls) conducted in California and Utah (1991-2002). CYP1A1 genotype was not associated with colon or rectal cancer. Having GSTM1 present, a CYP1A1 variant allele, and the rapid-acetylator NAT2 imputed phenotype was associated with increased risk of colon cancer (odds ratio = 1.7, 95% confidence interval: 1.2, 2.3). Among men, the greatest colon cancer risk was observed for having any CYP1A1 variant allele and currently smoking (odds ratio = 2.5, 95% confidence interval: 1.3, 4.8; Wald chi(2) test: p < 0.01). Assessment of GSTM1 and CYP1A1 and rectal cancer in men showed a twofold elevation in risk for more than 20 pack-years of smoking, except among those with GSTM1 present who had a variant CYP1A1 allele. These data support the association between smoking and colon and rectal cancer. Smoking may have a greater impact on colorectal cancer risk based on CYP1A1 genotype; this might further be modified by GSTM1 for rectal cancer risk.
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