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Androgen receptor polymorphisms: Association with prostate cancer risk, relapse and overall survival
Author(s) -
Edwards Stephen M.,
Badzioch Mike D.,
Minter Ralph,
Hamoudi Rifat,
Collins Nadine,
ArdernJones Audrey,
Dowe Anna,
Osborne Simon,
Kelly Jo,
Shearer Robert,
Easton Doug F.,
Saunders Grady F.,
Dearnaley David P.,
Eeles Rosalind A.
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19991022)84:5<458::aid-ijc2>3.0.co;2-y
Subject(s) - medicine , prostate cancer , androgen receptor , oncology , odds ratio , allele , hazard ratio , proportional hazards model , prostate , cancer , confidence interval , biology , genetics , gene
Several reports have suggested that one or both of the trinucleotide repeat polymorphisms in the human androgen receptor (hAR) gene, (CAG) n coding for polyglutamine and (GGC) n coding for polyglycine, may be associated with prostate cancer risk; but no study has investigated their association with disease progression. We present here a study of both hAR trinucleotide repeat polymorphisms not only as they relate to the initial diagnosis but also as they are associated with disease progression after therapy. Lymphocyte DNA samples from 178 British Caucasian prostate cancer patients and 195 control individuals were genotyped by PCR for the (CAG) n and (GGC) n polymorphisms in hAR. Univariate Cox proportional hazard analysis indicated that stage, grade and GGC repeat length were individually significant factors associated with disease‐free survival (DFS) and overall survival (OS). The relative risk (RR) of relapse for men with more than 16 GGC repeats was 1.74 (95% CI 1.08–2.79) and of dying from any cause, 1.98 (1.13–3.45). Adjusting for stage and grade, GGC effects remained but were not significant (RR DFS = 1.60, p = 0.052; RR OS = 1.65, p = 0.088). The greatest effects were in stage T1‐T2 (RR DFS = 3.56, 95% CI 1.13–11.21) and grade 1 (RR DFS = 6.47, 95% CI 0.57–72.8) tumours. No differences between patient and control allele distributions were found by odds‐ratio analysis, nor were trends with stage or grade evident in the proportion of short CAG alleles. Non‐significant trends with stage and grade were found in the proportion of short GGC alleles. The (GGC) n polymorphism in this population is a significant predictor of disease outcome. Since the (GGC) n effect is strongest in early‐stage tumours, this marker may help forecast aggressive behaviour and could be used to identify those patients meriting more radical treatment. Int. J. Cancer (Pred. Oncol.) 84:458–465, 1999. © 1999 Wiley‐Liss, Inc.