Esophageal cancer risk in relation to GGC and CAG trinucleotide repeat lengths in the androgen receptor gene

Authors

  • Erin Dietzsch,

    1. MRC/UCT Oesophageal Cancer Research Group, Division of Medical Biochemistry, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa
    Search for more papers by this author
  • Ria Laubscher,

    1. Biostatistics Unit, Medical Research Council, Parow Valley, South Africa
    Search for more papers by this author
  • M. Iqbal Parker

    Corresponding author
    1. MRC/UCT Oesophageal Cancer Research Group, Division of Medical Biochemistry, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa
    • Division of Medical Biochemistry, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa
    Search for more papers by this author
    • Fax: +27-21-447-3762 or +27-21-447-7669


Abstract

The incidence of esophageal squamous cell cancer in African males in South Africa is one of the highest in the world. Because most patients present with advanced disease such that survival is poor, the identification of high-risk individuals will facilitate early disease detection. Two polymorphic triplet repeats—(CAG)n and (GGC)n—in the androgen receptor gene were evaluated as potential genetic susceptibility loci for esophageal squamous cell cancer. Shorter lengths of these alleles have been reported to be associated with increased risk for prostate cancer. Our study sample comprised African males (29 patients and 109 controls), African females (14 patients and 59 controls) and Colored males (15 patients and 58 controls) whose alleles were analyzed singly and in combination. As in prostate cancer, the short (GGC)n alleles were implicated in esophageal cancer in African males: the average allele length was significantly shorter in patients compared to controls (p = 0.018), and a short (GGC)n allele was associated with elevated risk for disease [(GGC)≤16 odds ratio (OR) 2.7, 95% confidence interval (CI) 1.14–6.36; (GGC)≤14 OR 3.3, 95% CI 1.29–8.44]. There was no evidence, however, that short (CAG)n repeat alleles increased susceptibility to the disease. When the 2 alleles were considered jointly, additional information on predisposition was gained, revealing 2 haplotypes conferring a protective effect, i.e., [(CAG)>21 (GGC)≤16] OR 0.31, 95% CI 0.11–0.88; [(CAG)≤21 (GGC)>16] OR 0.26, 95% CI 0.11–0.65. Analysis using logistic regression led to narrower CIs for the ORs and enabled presentation of a risk profile. © 2003 Wiley-Liss, Inc.

Ancillary