CYP1A1, cigarette smoking, and colon and rectal cancer.
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.
Slattery
Martha L
ML
Health Research Center, University of Utah Health Sciences Center, Salt Lake City, UT 84108, USA. mslatter@hrc.utah.edu
Samowtiz
W
W
Ma
K
K
Murtaugh
M
M
Sweeney
C
C
Levin
T R
TR
Neuhausen
S
S
D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D003043:Cocarcinogenesis; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000209:etiology*; D014644:Genetic Variation; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D017720:Molecular Epidemiology; D010641:Phenotype; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism / Q000506:poisoning; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics; D012907:Smoking / Q000009:adverse effects*; D014589:Utah / Q000453:epidemiology
D020413:3' Untranslated Regions; D001191:Arylamine N-Acetyltransferase; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D008565:Membrane Proteins; D011084:Polycyclic Aromatic Hydrocarbons; D012697:Serine Endopeptidases; C478900:NAT2 protein, human; C429035:TMPRSS13 protein, human