Detection of UGT1A10 polymorphisms and their association with orolaryngeal carcinoma risk.
BACKGROUND
UGT1A10 exhibits glucuronidating activity against metabolites of the tobacco smoke carcinogen, benzo(a)pyrene, and is expressed highly in numerous target tissues for tobacco-related cancers including the upper aerodigestive tract. The current study was conducted to determine the prevalence of genetic polymorphisms in the UGT1A10-specific region of the UDP-glucuronosyltransferase family 1A locus and their relationship with risk for orolaryngeal carcinoma.


METHODS
The authors analyzed UGT1A10-specific sequences in a population of black, white, and Asian individuals. Ten UGT1A10 alleles were identified by direct sequencing of UGT1A10 sequences amplified by polymerase chain reaction (PCR) using DNA purified from buccal cell swabs that were taken from individual subjects.


RESULTS
In addition to three silent polymorphisms, three missense polymorphisms were found at codons 139 (Glu > Lys), 240 (Thr > Met), and 244 (Leu > Ile). Using PCR-restriction fragment length polymorphism analysis of buccal cell DNA, the prevalence of the UGT1A10(240Met) variant was less than 0.01% in whites and blacks. Similarly, the prevalence of both the UGT1A10(139Lys) and UGT1A10(244Ile) variants was less than 0.01% in whites but it was significantly higher (0.04 and 0.05, respectively, P < 0.01) in blacks. None of the missense UGT1A10 variants were found in any of the Asian individuals examined. In a case-control study of black individuals, a significant association with orolaryngeal carcinoma risk was found in persons with at least 1 UGT1A10(139Lys) allele (crude odds ratio, 0.29 [95% confidence interval, 0.10-0.81]; adjusted odds ratio, 0.20 [95% confidence interval, 0.05-0.87]). No association was observed for the codon 244 (Leu > Ile) polymorphism.


CONCLUSIONS
The data from the current study show that the UGT1A10 gene has several low-frequency missense polymorphisms and that the codon 139 polymorphism is an independent risk factor for orolaryngeal carcinoma in blacks.
Elahi
Abul
A
Cancer Epidemiology and Prevention Program, H. Lee Moffitt Cancer Center, Department of Interdisciplinary Oncology, University of South Florida, Tampa, Florida 33612, USA.
Bendaly
Jean
J
Zheng
Zhong
Z
Muscat
Joshua E
JE
Richie
John P
JP
Schantz
Stimson P
SP
Lazarus
Philip
P
D000428:Alcohol Drinking / Q000009:adverse effects; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D005787:Gene Frequency; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D020125:Mutation, Missense; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D044469:Racial Groups; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
C476725:bilirubin uridine-diphosphoglucuronosyl transferase 1A10; D014453:Glucuronosyltransferase