Androgen receptor polymorphisms and endometrial cancer risk

Monica McGrath, I. Min Lee, Susan E. Hankinson, Peter Kraft, David J. Hunter, Julie Buring, Immaculata De Vivo

Research output: Contribution to journalArticlepeer-review

Abstract

The androgen receptor (AR) gene is a transcription factor responsible for mediating the physiological effects of androgens. Evidence suggests that androgens and the androgen receptor are involved in uterine cell proliferation. A polymorphic CAG repeat in exon 1 of the AR gene encodes a polyglutamine tract that is inversely correlated with the transcriptional activity of this gene. We assessed the association between the functional CAG repeat polymorphism and AR haplotypes and the risk of endometrial cancer in two nested case-control studies within the Nurses' Health Study (n = 222 cases, 666 controls) and the Women's Health Study (n = 137 cases, 411 controls) using conditional and unconditional logistic regression. Associations between AR CAG repeat polymorphism and endometrial cancer risk were similar in the 2 case-control studies. In the pooled analysis, women with an average repeat allele ≥22 repeats compared to <22 repeats were at a statistically significant decreased risk of endometrial cancer (odds ratio (OR) = 0.76; 95% confidence interval (CI), 0.59-0.98). Women with one or two long alleles (≥27 repeats) compared to both alleles <22 repeats were also at a statistically significant decreased risk (OR = 0.60; 95% CI, 0.36-0.99). We observed a modest yet statistically significant association for each one unit increase in the average repeat length and endometrial cancer risk (OR = 0.94; 95% CI, 0.88-1.00). Associations for the AR CAG average repeat length and endometrial cancer risk differed by menopausal status (p = 0.02). No significant associations between the AR haplotypes and endometrial cancer risk were observed. Our findings suggest that an increasing number of functional CAG repeats may be associated with endometrial carcinogenesis because of AR's reduced ability to recruit coregulators and other transcriptional components, (supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/ suppmat/index.html).

Original languageEnglish (US)
Pages (from-to)1261-1268
Number of pages8
JournalInternational Journal of Cancer
Volume118
Issue number5
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

Keywords

  • Androgen receptor
  • Endometrial cancer
  • Epidemiology
  • Polymorphisms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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