title: Association between exposure-relevant polymorphisms in CYP1B1, EPHX1, NQO1, GSTM1, GSTP1 and GSTT1 and risk of colorectal cancer in a Czech population.
abstract: Associations of functional single nucleotide polymorphisms in cytochrome P450 1B1, epoxide hydrolase 1, NAD(P)H:quinone oxidoreductase 1, glutathione S-transferase Pi-1 and deletions of glutathione S-transferases Mu-1 and θ-1 with colorectal cancer risk were investigated in a hospital-based case-control study on 495 matched pairs of Czech Caucasians. Polymorphisms were assessed by polymerase chain reaction restriction fragment length polymorphism-based methods, allele-specific multiplex and allelic discrimination by real-time polymerase chain reaction. Carriers of variant Ser allele in codon 453 of cytochrome P450 1B1 (rs1800440) were at a significantly lower risk of colorectal cancer compared to carriers of the wild-type allele (adjusted odds ratio, aOR=0.68, CI=0.51-0.89, p=0.006). The combination of polymorphisms in codons 453 and 432 (rs1056836) of cytochrome P450 1B1 further increased the protective effect (aOR=0.53, CI=0.34-0.83, p=0.005). The glutathione S-transferase Mu-1 deletion was associated with a moderately elevated colorectal cancer risk (aOR=1.30, CI=1.01-1.68, p=0.044). Combination of glutathione S-transferase Mu-1 and θ-1 deletion was associated with a significantly higher colorectal cancer risk compared to the presence of both full-length genes (aOR=1.58, CI=1.01-2.47, p=0.044). Genetic polymorphisms in glutathione S-transferase Pi-1, NAD(P)H:quinone oxidoreductase 1, epoxide hydrolase 1 and deduced epoxid hydrolase 1 activity did not modify the risk of colorectal cancer. These results provide further evidence that interaction between metabolic gene variants contributes to colorectal carcinogenesis.
authors.affiliation: Toxicogenomics Unit, National Institute of Public Health, 100 42 Prague, Czech Republic.
authors.forename: Ivona
authors.initials: I
authors.lastname: Hlavata
authors.forename: David
authors.initials: D
authors.lastname: Vrana
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Smerhovsky
authors.forename: Barbara
authors.initials: B
authors.lastname: Pardini
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodicka
authors.forename: Jan
authors.initials: J
authors.lastname: Novotny
authors.forename: Beatrice
authors.initials: B
authors.lastname: Mohelnikova-Duchonova
authors.forename: Pavel
authors.initials: P
authors.lastname: Soucek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D018153:Czech Republic; D004851:Epoxide Hydrolases / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System; D004851:Epoxide Hydrolases; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D016660:NAD(P)H Dehydrogenase (Quinone); C585496:CYP1B1 protein, human; C447479:NQO1 protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; C522330:EPHX1 protein, human