title: Effects of genetic polymorphisms of MDR1, FMO3 and CYP1A2 on susceptibility to colorectal cancer in Koreans.
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.
authors.affiliation: Department of Surgery, Inha Institute of Research for Medical Sciences, College of Medicine, Inha University, Incheon 410-712, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Bae
authors.forename: Sun-Keun
authors.initials: SK
authors.lastname: Choi
authors.forename: Kyung-Rae
authors.initials: KR
authors.lastname: Kim
authors.forename: Chang-Shin
authors.initials: CS
authors.lastname: Park
authors.forename: Sung-Keun
authors.initials: SK
authors.lastname: Lee
authors.forename: Hyung-Keun
authors.initials: HK
authors.lastname: Roh
authors.forename: Dong-Woon
authors.initials: DW
authors.lastname: Shin
authors.forename: Jae-Eun
authors.initials: JE
authors.lastname: Pie
authors.forename: Ze-Hong
authors.initials: ZH
authors.lastname: Woo
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Kang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000368:Aged; D044466:Asian People / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D010105:Oxygenases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D019388:Cytochrome P-450 CYP1A2