Effects of genetic polymorphisms of MDR1, FMO3 and CYP1A2 on susceptibility to colorectal cancer in Koreans

Cancer Sci. 2006 Aug;97(8):774-9. doi: 10.1111/j.1349-7006.2006.00241.x. Epub 2006 Jun 23.

Abstract

The aim of the present study was to evaluate the effects on the susceptibility to colorectal cancer (CRC) of genetic polymorphisms in P-glycoprotein (PGP) and the metabolic enzymes cytochrome P450 1A2 (CYP1A2) and flavin-containing monooxygenase 3 (FMO3). We analyzed five single-nucleotide polymorphisms (SNP) in 93 cancer-free volunteers and 111 patients with CRC: one common genetic variant of the PGP-encoding MDR1 gene and four SNP in genes for metabolic enzymes (two SNP in FMO3 and two SNP in CYP1A2). The genotypes and allele frequencies of the MDR1/C3435T, FMO3/G488A, FMO3/A923G and CYP1A2/G-3860 A polymorphisms were not significantly different in cancer-free subjects and CRC patients. However, a significant association was found between the CYP1A2/A-163C polymorphism and the risk of CRC, particularly in elderly (>55 years) subjects and smokers. A phenotyping study in normal smokers showed that the CYP1A2 activity of subjects with the CYP1A2/-163 AA genotype was significantly lower than that of subjects carrying the CYP1A2/-163C allele. Combined results show that the CYP1A2/-163C allele is significantly associated with an increase in CYP1A2 activity and a consequent increased risk of CRC in Koreans, particularly in elderly people and smokers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Aged
  • Asian Continental Ancestry Group / genetics
  • Colorectal Neoplasms / genetics*
  • Cytochrome P-450 CYP1A2 / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Korea
  • Male
  • Middle Aged
  • Oxygenases / genetics*
  • Polymorphism, Single Nucleotide*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Oxygenases
  • dimethylaniline monooxygenase (N-oxide forming)
  • Cytochrome P-450 CYP1A2