Shorter CAG repeat length in the AR gene is associated with poor outcome in head and neck cancer

Arch Oral Biol. 2007 Aug;52(8):732-9. doi: 10.1016/j.archoralbio.2006.12.021. Epub 2007 Feb 23.

Abstract

Objective: Alterations in the size of the [CAG](n) repeats of the AR gene have been described in several types tumors. The purpose of this study was to evaluate if there is an association between the AR [CAG](n) repeat alleles and the relative risk for head and neck cancer and to analyse microsatellite instability (MSI) and loss of heterozygosity (LOH) in these tumors.

Design: Matched samples of blood and head and neck tumors were evaluated using two methodologies, silver-stained gels to perform the analyses of MSI and LOH, and automated analysis to confirm these results and for genotyping of the AR [CAG](n) repeat length. Sixty-nine individuals without cancer were used as a control group for both procedures. The Log-rank test was used to compare overall survival and disease-free survival curves. The Cox proportional hazards regression models were performed to determine the [CAG](n) repeats as an independent prognostic factor.

Results: Patients with alleles <or=20 in the male group showed a correlation with lower disease-free survival (P=0.0325) and with recurrence or metastasis (RR 2.52, CI 95%). In the female group, the allele 2 (longer allele) showed a significant lower mean of [CAG](n) repeat when compared to the control group. Microsatellite instability was detected in nine cases in both procedures. In six out of these nine cases, we observed a reduction of the AR [CAG](n) repeat length. LOH was detected in one out of 17 women informative for oral cancer in both procedures.

Conclusion: These results suggest that short [CAG](n) repeat length (<or=20) polymorphism is associated with poor prognosis in a subset of male patients with head and neck cancer and that AR gene microsatellite instability is uncommon in these tumors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Case-Control Studies
  • Cytosine*
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Guanine*
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Loss of Heterozygosity / genetics
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Neoplasm Metastasis / genetics
  • Neoplasm Recurrence, Local / genetics
  • Polymorphism, Genetic / genetics
  • Prognosis
  • Receptors, Androgen / genetics*
  • Sex Factors
  • Survival Rate
  • Trinucleotide Repeats / genetics*

Substances

  • Receptors, Androgen
  • Guanine
  • Cytosine
  • Adenine