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Detection of UGT1A10 polymorphisms and their association with orolaryngeal carcinoma risk

  1. Abul Elahi Ph.D.1,†,
  2. Jean Bendaly M.S.1,†,
  3. Zhong Zheng M.D., Ph.D.1,
  4. Joshua E. Muscat Ph.D., M.P.H.2,
  5. John P. Richie Jr. Ph.D.2,
  6. Stimson P. Schantz M.D.3,
  7. Philip Lazarus Ph.D.1,4,5,‡,*

Article first published online: 1 JUL 2003

DOI: 10.1002/cncr.11587

Issue

Cancer

Cancer

Volume 98, Issue 4, pages 872–880, 15 August 2003

Additional Information

How to Cite

Elahi, A., Bendaly, J., Zheng, Z., Muscat, J. E., Richie, J. P., Schantz, S. P. and Lazarus, P. (2003), Detection of UGT1A10 polymorphisms and their association with orolaryngeal carcinoma risk. Cancer, 98: 872–880. doi: 10.1002/cncr.11587

Author Information

  1. 1

    Cancer Epidemiology and Prevention Program, H. Lee Moffitt Cancer Center, Department of Interdisciplinary Oncology, University of South Florida, Tampa, Florida

  2. 2

    Division of Epidemiology and Cancer Susceptibility, American Health Foundation, Valhalla, New York

  3. 3

    Department of Otolaryngology, The New York Eye and Ear Infirmary, New York, New York

  4. 4

    Department of Biochemistry and Molecular Biology, University of South Florida, Tampa, Florida

  5. 5

    Department of Pharmacology and Therapeutics, University of South Florida, Tampa, Florida

  1. †

    Dr. Elahi and Mr. Bendaly contributed equally to this work.

  2. ‡

    Fax: (813) 632-1328

*H. Lee Moffitt Cancer Center, University of South Florida, 12902 Magnolia Drive, MRC-2E, Tampa, FL 33612

Publication History

  1. Issue published online: 1 AUG 2003
  2. Article first published online: 1 JUL 2003
  3. Manuscript Accepted: 19 MAY 2003
  4. Manuscript Revised: 13 MAY 2003
  5. Manuscript Received: 10 APR 2003

Funded by

  • Public Health Service (PHS). Grant Numbers: DE12206, DE13158
  • National Institutes of Health and Human Services. Grant Number: CA68384

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Keywords:

  • oral carcinoma;
  • UDP-glucuronosyltransferase;
  • UGT1A10;
  • tobacco carcinogenesis;
  • polymorphism

Abstract

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 UGT1A10240Met variant was less than 0.01% in whites and blacks. Similarly, the prevalence of both the UGT1A10139Lys and UGT1A10244Ile 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 UGT1A10139Lys 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. Cancer 2003;98:872–80. © 2003 American Cancer Society.

DOI 10.1002/cncr.11587

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