Author/Editor		Dolžan, Vita; Ravnik-Glavač, Metka; Breskvar, Katja
Title		Genetic polymorphisms of xenobiotic metabolizing enzymes in human colorectal cancer
Translated title		Genetski polimorfizem encimov, ki presnavljajo ksenobiotike pri kolorektalnem raku
Type		članek
Source		Radiol Oncol
Vol. and No.		Letnik 32, št. 1
Publication year		1998
Volume		str. 35-9
Language		eng
Abstract		It was proposed that both hereditary and environmental factors contribute to the development of colorectal cancer (CRC). Carcinogenic polycyclic aromatic hydrocarbons (PAHs) from food or tobacco smoke can form DNA adducts and thus initiate carcinogenesis after metabolic activation via cytochrome P4501A1 (CYP1A1). Intermediate metabolites are detoxified by conjugation with glutathione S-transferases. Our aim was to look for inherited metabolic suceptibility to CRC. We used PCR-based genotyping approach to determine the frequencies of polymorphic alleles of two cytochromes P450 (CYP2D6 and CYP1A1) and two glutathione S-transferases (GSTM1 and GSTT1) in DNA samples from 31 sporadic, 25 familial CRC cases and 73 healthy controls. The difference in frequencies of poor metabolisers due to CYP2D6 gene polymorphism was close to the limit of statistical significance between sporadi CRC and healthy control group (lambda 2=5.52, m=2, p=0.06) despite the small sample size. The frequencies of either CYP1A1 MspI, GST M1 or GST T1 genotypes were not significantly different in both CRC cases and in controls. Although our study suggests some difference in metabolic susceptibility between sporadic and familial CRC, further studies are needed to investigate the combined effect of polymorphic genes involved in carcinogen metabolism in a larger group of patients with defined exposure to dietary carcinogens and smoking.
Descriptors		COLORECTAL NEOPLASMS POLYMORPHISM (GENETICS) CYTOCHROME P-450 CYP1A1 CYTOCHROME P-450 CYP2D6 GLUTATHIONE TRANSFERASES POLYMERASE CHAIN REACTION