Balkan Journal of Medical Genetics

CAG REPEAT NUMBER IN THE ANDROGEN RECEPTOR GENE AND PROSTATE CANCER
Madjunkova S, Eftimov A, Georgiev V, Petrovski D, Dimovski AJ, Plaseska- Karanfi lska D,
*Corresponding Author: Professor Dr. Dijana Plaseska-Karanfi lska, Macedonian Academy of Sciences and Arts, Research Center for Genetic Engineering and Biotechnology “Georgi D. Efremov”, Av. Krste Misirkov 2, POB 428, 1000 Skopje, Republic of Macedonia; Tel.: +389-2-3235-410; Fax: +389-2-3115- 434; E-mail: dijana@manu.edu.mk
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DISCUSSION

The hypothesis that variation in transcriptional activity of the AR related to polymorphic CAG repeats [27] infl uences prostate carcinogenesis [28], has been tested in many studies. The results have not been in full agreement, some fi nding moderateto- signifi cant association of short CAG repeats with increased PC risk, others failing to confi rm this. Our results suggest that a shorter CAG repeat length (<19) is associated with an increased risk of PC. This agrees with previous reports that short CAG repeat lengths in the AR gene predisposes to PC [14,29,30]. However others, studying French- German populations [31] and North American populations [20,32], have reported no such association. The association between PC and increasing age is very strong [33]. In our study the same proportion of patients with PC and with BPH (about 2/3) was diagnosed at >65 years, and we found no association between short CAG repeat length and age at diagnosis. This supports the importance of age as an independent risk factor for PC and BPH [34]. To test if short CAG repeats may predispose to more aggressive forms of PC [14,35], we performed a case analysis according to Gleason score and found an association between repeat length <19 and low grade PC tumors (Gleason score <7). For advanced disease, we observed a suggestive lower risk with fewer CAG repeats, unlike in the Physicians’ Health Study [36], which showed a monotonically increasing risk with decreasing number of CAG repeats for advanced cases. The possible explanation is that androgens may infl uence the stage and grade of PC independently, and the increased androgenic stimulation in PC patients with lower CAG repeat length and subsequently higher AR activity, may prevent the dedifferentiation of the prostate epithelium in the nascent tumor [37]. This needs to be clarifi ed and further investigated to determine the infl uence of androgens on differentiation status in cases that are restricted to uniform stage. We found that CAG repeat length was not signifi cantly different in BPH patients than in controls (p = 0.9166) but was signifi cantly different between PC and BPH (p = 0.038). This agrees with previous studies and the Prostate Cancer Prevention Trial [38,39]. Our results suggest the possibility that the risk of malignancy is not higher in BPH patients than in controls, and that BPH is an independent entity and is not a precancerous state [40]. We conclude that short CAG repeats (<19) may be associated with increased PC risk in Macedonian men and that our results provide potential tools to assist in prediction strategies for this important disease.

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