Combined analysis of polymorphisms in glutathione S-transferase M1 and microsomal epoxide hydrolase in lung cancer patients.
Many genes involved in the metabolism of carcinogens have been found to be polymorphic in the human population, and specific alleles are associated with increased risk of cancer at various sites. The etiology of most commonly occurring cancers cannot be explained by allelic variability at a single locus. A combined analysis of two polymorphic enzymes, glutathione S-transferase M1 (GSTM1), microsomal epoxide hydrolase (EPHX1)) and their implication as lung cancer risk factors was performed in a case- control study of non small cell lung cancer. Polymerase chain reaction (PCR) or PCR-RFLP-based methods were used to detect variant genotypes of GSTM1 and EPHX1 (113Tyr-113His in exon 3 and 139His-139Arg in exon 4) in 150 controls and group of lung cancer patients (n=121). The slow 113His EPHX1 allele tended to be more frequent among the patients (frequency 0.587) than among the controls (0.320) (Fisher s exact test, p=0.33). The combined EPHX1 homozygote genotype His113/His139 (predicted very slow activity) versus all other genotype combination was associated with an increased risk of lung cancer (OR=2.29; 95% C.I.=0.94- 5.82), particularly in non-smokers (OR=11.23; 95% C.I.=1.48- 88.41). Polymorphism in GSTM1 had no statistically significant impact on lung cancer risk alone (OR=1.09; 95% C.I.: 0.65-1.82). However, obtained the results revealed that combinations GSTM1 null with homozygote His113/His139 genotype (predicted very slow activity EPHX1) significantly increased lung cancer risk (OR=3.65; 95% C.I.: 1.04-16.07). No overall relationship between genotype combinations predicted high EPHX1 activity and lung cancer risk was confirmed in all followed respects. However, the number of investigated individuals in our study was relatively small, therefore these findings should be judged with circumspectness.
Habalová
V
V
Department of Medical Biology, Medical Faculty of P.J. Safárik University, 040 66 Kosice, Slovak Republic. habalova@central.nedic.upjs.sk
Salagovic
J
J
Kalina
I
I
Stubna
J
J
D000368:Aged; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics*; D017931:DNA Primers; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012907:Smoking
D017931:DNA Primers; D004851:Epoxide Hydrolases; D005982:Glutathione Transferase