Polymorphisms of xenobiotic metabolizing genes in oropharyngeal carcinoma.
OBJECTIVE
The objective was to determine the prevalence of the polymorphisms of the microsomal epoxide hydrolase (Ephx1), glutathione S-transferase mu1 (GSTM ), theta1 (GSTT1), and pi1 (GSTP1) genes in patients with oropharyngeal carcinoma.


METHODS
Gene polymorphisms in 137 patients with oropharyngeal carcinoma were determined by polymerase chain reaction and restriction enzyme digestion for xenobiotic metabolizing enzymes that have been implicated in the carcinogenesis of tobacco-related neoplasias and compared with a population sample of 99 persons.


RESULTS
At Ephx1 (microsomal epoxide hydrolase) codon 113, an overrepresentation of the greater activity genotype (Tyr/Tyr) was observed for male ever-smokers alone, both male and female ever-smokers, female never-smokers alone, and in both male and female never-smokers, compared with a control population sample. At codon 139, Ephx1 showed no differences. There was an overrepresentation of homozygosity for the GSTT1 (glutathione S-transferase theta1) null allele [but not for the GSTM1 (glutathione S-transferase mu1) null allele] in ever-smokers, when compared with controls. Polymorphisms at the GSTP1 (glutathione S-transferase pi1) locus did not show differences versus controls, although in the never-smoker cancer sample there was a higher prevalence of the B/B genotype compared with ever-smokers.


CONCLUSIONS
The Ephx1 codon 113 Tyr/Tyr variant, as well as homozygosity for the GSTT1 null allele, is associated with oropharyngeal carcinogenesis.
Amador
Armando G
AG
Department of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis 46202-5186, USA.
Righi
Paul D
PD
Radpour
Shokri
S
Everett
Eric T
ET
Weisberger
Edward
E
Langer
Mark
M
Eckert
George J
GJ
Christen
Arden G
AG
Campbell
Samuel
S
Summerlin
Don-Jon
DJ
Reynolds
Nichole
N
Hartsfield
James K
JK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001224:Aspartic Acid / Q000235:genetics; D002277:Carcinoma / Q000201:enzymology* / Q000235:genetics; D003062:Codon / Q000235:genetics; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006639:Histidine / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000201:enzymology* / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012737:Sex Factors; D013223:Statistics as Topic; D014443:Tyrosine / Q000235:genetics
D001224:Aspartic Acid; D003062:Codon; D004851:Epoxide Hydrolases; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D006639:Histidine; D007527:Isoenzymes; D014443:Tyrosine; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human