title: A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of colorectal cancer.
abstract: OBJECTIVE
  Sporadic colorectal cancer (CRC) is considered a multifactorial disease where multiple exposures interact with the individual genetic background resulting in risk modulation. We performed an association study aimed to investigate the role of single nucleotide polymorphisms (SNPs) within genes of phase I (CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2D6, CYP2E1, CYP2C9, CYP2C19, CYP3A4, ADH2, EPHX1) and phase II of the xenobiotic metabolism (ALDH2, COMT, GSTA2, GSTA4, GSTM1, GSTM3, GSTP1, GSTT2, MTHFR, NAT1, NAT2, NQO1, MnSOD2, SULT1A1, TPMT).
  
  
  METHODS
  We genotyped 377 cases and 326 controls, by use of an oligonucleotide micro-array and the arrayed primer extension technique (APEX).
  
  
  RESULTS
  N-acetyl-transferase 1 'rapid' phenotype and CYP1A2 -164C>A carriers were associated with increased risk of CRC, confirming data reported in previous studies. Interestingly, homozygotes for allele 48G within CYP1B1, a variant with an increased activity towards several substrates including sex hormones, were at increased risk (OR=2.81, 95% CI 1.32-5.99). Moreover, CYP1A1 SNPs T461N and -1738A>C were associated with a reduced risk of cancer (OR=0.52; 95% CI 0.31-0.88 and OR=0.69, 95% CI 0.50-0.94 for carriers, respectively).
  
  
  CONCLUSIONS
  The present data suggest a role for CYP1B1 and CYP1A1 as new candidate genes in the etiology of CRC and confirm the carcinogenic role of aromatic amines metabolism for colorectum.
authors: Genetica, Dip. Scienze Uomo e Ambiente, University of Pisa, Italy.
authors: Stefano
authors: S
authors: Landi
authors: Federica
authors: F
authors: Gemignani
authors: Victor
authors: V
authors: Moreno
authors: Lydie
authors: L
authors: Gioia-Patricola
authors: Amélie
authors: A
authors: Chabrier
authors: Elisabeth
authors: E
authors: Guino
authors: Matilde
authors: M
authors: Navarro
authors: Javier
authors: J
authors: de Oca
authors: Gabriel
authors: G
authors: Capellà
authors: Federico
authors: F
authors: Canzian
mesh_terms: D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics*; D004798:Enzymes / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D004798:Enzymes; D015262:Xenobiotics