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Cancer Prevention Research
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Research Article

Loss of Heterozygosity (LOH) Profiles—Validated Risk Predictors for Progression to Oral Cancer

Lewei Zhang, Catherine F. Poh, Michele Williams, Denise M. Laronde, Ken Berean, Pamela J. Gardner, Huijun Jiang, Lang Wu, J. Jack Lee and Miriam P. Rosin
Lewei Zhang
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
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Catherine F. Poh
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
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Michele Williams
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
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Denise M. Laronde
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
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Ken Berean
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
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Pamela J. Gardner
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
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Huijun Jiang
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
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Lang Wu
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
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J. Jack Lee
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
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Miriam P. Rosin
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
Authors' Affiliations: 1Cancer Control Research Department, 2Oral Oncology Department, 3Fraser Valley Program in Oral Oncology/Dentistry, British Columbia Cancer Agency; 4Faculty of Dentistry and Departments of 5Pathology and Laboratory Medicine and 6Statistics, University of British Columbia, Vancouver; 7Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and 8Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
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DOI: 10.1158/1940-6207.CAPR-12-0173 Published September 2012
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Abstract

A major barrier to oral cancer prevention has been the lack of validated risk predictors for oral premalignant lesions (OPL). In 2000, we proposed a loss of heterozygosity (LOH) risk model in a retrospective study. This paper validated the previously reported LOH profiles as risk predictors and developed refined models via the largest longitudinal study to date of low-grade OPLs from a population-based patient group. Analysis involved a prospective cohort of 296 patients with primary mild/moderate oral dysplasia enrolled in the Oral Cancer Prediction Longitudinal Study. LOH status was determined in these OPLs. Patients were classified into high-risk or low-risk profiles to validate the 2000 model. Risk models were refined using recursive partitioning and Cox regression analyses. The prospective cohort validated that the high-risk lesions (3p and/or 9p LOH) had a 22.6-fold increase in risk (P = 0.002) compared with low-risk lesions (3p and 9p retention). Addition of another 2 markers (loci on 4q/17p) further improved the risk prediction, with five-year progression rates of 3.1%, 16.3%, and 63.1% for the low-, intermediate-, and high-risk lesions, respectively. Compared with the low-risk group, intermediate- and high-risk groups had 11.6-fold and 52.1-fold increase in risk (P < 0.001). LOH profiles as risk predictors in the refined model were validated in the retrospective cohort. Multicovariate analysis with clinical features showed LOH models to be the most significant predictors of progression. LOH profiles can reliably differentiate progression risk for OPLs. Potential uses include increasing surveillance for patients with elevated risk, improving target intervention for high-risk patients while sparing a large number of low-risk patients from needless screening and treatment. Cancer Prev Res; 5(9); 1081–9. ©2012 AACR.

See Perspectives on p. 1073 and p. 1075

  • Received April 17, 2012.
  • Revision received May 17, 2012.
  • Accepted July 5, 2012.
  • ©2012 American Association for Cancer Research.

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Cancer Prevention Research: 5 (9)
September 2012
Volume 5, Issue 9
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Loss of Heterozygosity (LOH) Profiles—Validated Risk Predictors for Progression to Oral Cancer
Lewei Zhang, Catherine F. Poh, Michele Williams, Denise M. Laronde, Ken Berean, Pamela J. Gardner, Huijun Jiang, Lang Wu, J. Jack Lee and Miriam P. Rosin
Cancer Prev Res September 1 2012 (5) (9) 1081-1089; DOI: 10.1158/1940-6207.CAPR-12-0173

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Loss of Heterozygosity (LOH) Profiles—Validated Risk Predictors for Progression to Oral Cancer
Lewei Zhang, Catherine F. Poh, Michele Williams, Denise M. Laronde, Ken Berean, Pamela J. Gardner, Huijun Jiang, Lang Wu, J. Jack Lee and Miriam P. Rosin
Cancer Prev Res September 1 2012 (5) (9) 1081-1089; DOI: 10.1158/1940-6207.CAPR-12-0173
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