Relationship of obesity, androgen receptor genotypes and biochemical failure after radical prostatectomy

Obesity and androgen metabolism have been implicated in the progression of prostate cancer. Obesity has been associated with increased risk for advanced disease and biochemical failure after treatment. This association may be the result of changes in androgen metabolism that occur with obesity and are mediated by the androgen receptor (AR).

To evaluate the effects of obesity and AR polymorphisms on biochemical failure, we conducted a study of 536 Caucasian prostate cancer cases. We determined the relationship between time to biochemical failure and obesity stratified by short and long AR-CAG and AR-GGN repeat sequence. The AR repeat groups were dichotomized at the median number of repeats for each polymorphism.

An association was found for obesity in the short CAG group (HR = 3.45, 95% CI = 1.00-11.96). Among obese patients diagnosed with localized disease (T1/T2), the risk of biochemical failure was significantly higher (HR = 7.05, 95% CI = 1.55-32.06). No difference was observed for high stage (T3/T4) obese patients. Additionally, no differences in biochemical failure were observed in obese and non-obese men grouped by number of AR-GGN repeats.

Obesity is significantly associated with increased risk of biochemical failure in men with the high-risk short CAG sequence on the AR gene. This effect is not observed in men with long CAG repeats. Therefore, it appears that the relationship between biochemical failure and obesity may be modified by the AR-CAG repeat pattern. The short AR-CAG genotype may be more responsive to an altered hormonal milieu created by obesity.