CYP1A1, cigarette smoking, and colon and rectal cancer

Am J Epidemiol. 2004 Nov 1;160(9):842-52. doi: 10.1093/aje/kwh298.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Aged
  • Arylamine N-Acetyltransferase / genetics
  • California / epidemiology
  • Case-Control Studies
  • Cocarcinogenesis
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / metabolism
  • Cytochrome P-450 CYP1A1 / genetics*
  • Cytochrome P-450 CYP1A1 / metabolism
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / etiology*
  • Genetic Variation
  • Genotype
  • Glutathione Transferase / genetics
  • Humans
  • Incidence
  • Logistic Models
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Molecular Epidemiology
  • Phenotype
  • Polycyclic Aromatic Hydrocarbons / metabolism
  • Polycyclic Aromatic Hydrocarbons / poisoning
  • Polymorphism, Genetic / genetics*
  • Risk Factors
  • Serine Endopeptidases / genetics
  • Smoking / adverse effects*
  • Utah / epidemiology


  • 3' Untranslated Regions
  • Membrane Proteins
  • Polycyclic Aromatic Hydrocarbons
  • Cytochrome P-450 CYP1A1
  • Arylamine N-Acetyltransferase
  • NAT2 protein, human
  • Glutathione Transferase
  • glutathione S-transferase M1
  • Serine Endopeptidases
  • TMPRSS13 protein, human