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How Strong Is the Association Between CAG and GGN Repeat Length Polymorphisms in the Androgen Receptor Gene and Prostate Cancer Risk?

¹ Department of Public Health and Epidemiology, School of Medicine, University of Birmingham, Birmingham, United Kingdom; ² Department of General Practice, Comprehensive Cancer Institute Limburg, Catholic University of Leuven, Leuven, Belgium; ³ Department of Epidemiology, Faculty of Health Sciences, Maastricht University, Maastricht, Netherlands; ⁴ Department of Urology and Epidemiology, University Medical Centre Nijmegen, Nijmegen, Netherlands; ⁵ Department of Urology, School of Medicine, University of Miami, Miami, Florida and ⁶ Human Genetics Program, School of Medicine, New York University, New York, New York

Requests for reprints: Maurice P. Zeegers, Department of Public Health and Epidemiology, School of Medicine, Public Health Building, University of Birmingham, Birmingham B15 2TT, United Kingdom. Phone: 44-121-414-6721; Fax: 44-121-414-7878. E-mail: M.P.Zeegers{at}bham.ac.uk

Objective: Although narrative reviews have suggested an association between (CAG)n and (GGN)n polymorphisms in the AR gene and prostate cancer, it has never been quantified systematically. The purpose of this meta-analysis was to provide relative and absolute quantitative summary estimates with sufficient power.

Method: Publications were identified through database searches for epidemiologic studies published until February 2004. For each study, mean differences in repeat length between cases and controls were calculated as well as continuous odds ratios (OR) per one CAG or GGN repeat decrement and discrete ORs to compare prostate cancer risk in men with short CAG repeats (21 repeats) versus long CAG repeats (>21 repeats) and short GGN repeats (16 repeats) versus long GGN repeats (>16 repeats). The study-specific estimates were combined by random effects metaregression analyses.

Results: Nineteen case-control studies were included in this review comprising a total of 4,274 cases and 5,275 controls. Prostate cancer cases had on average 0.26 fewer CAG repeats and 0.09 fewer GGN repeats than controls. The continuous ORs of prostate cancer per one repeat decrement were 1.02 and 1.01 for CAG and GGN repeats, respectively. The summary discrete OR (95% confidence interval) were 1.19 (1.07-1.31) and 1.31 (1.06-1.61) for CAG and GGN repeat polymorphisms, respectively.

Conclusion: Although the presence of shorter repeats seemed to be modestly associated with prostate cancer risk, the absolute difference in number of repeats between cases and controls is <1 repeat. We question whether such a small difference is enough to yield measurable biological impact in prostate carcinogenesis.

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