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印度南部男性雄激素受体基因中的GGN重复长度和GGN/CAG单倍型变异与前列腺癌风险

GGN repeat length and GGN/CAG haplotype variations in the androgen receptor gene and prostate cancer risk in south Indian men.

作者信息

Vijayalakshmi Krishnaswamy, Thangaraj Kumarasamy, Rajender Singh, Vettriselvi Venkatesan, Venkatesan Perumal, Shroff Sunil, Vishwanathan K N, Paul Solomon F D

机构信息

Department of Human Genetics, Sri Ramachandra Medical College and Research Institute (Deemed University), Porur, Chennai, 600116, Tamil Nadu, India.

Centre for Cellular and Molecular Biology, Hyderabad, India.

出版信息

J Hum Genet. 2006;51(11):998-1005. doi: 10.1007/s10038-006-0051-z. Epub 2006 Sep 13.

Abstract

The ethnic variation in the GGN and CAG microsatellites of the androgen receptor (AR) gene suggests their role in the substantial racial difference in prostate cancer risk. Hence, we performed a case-control study to assess whether GGN repeats independently or in combination with CAG repeats were associated with prostate cancer risk in South Indian men. The repeat lengths of the AR gene determined by Gene scan analysis, revealed that men with GGN repeats <or=21 had no significant risk compared to those with >21 repeats (OR 0.91 at 95% CI-0.52-1.58). However, when CAG repeats of our earlier study was combined with the GGN repeat data, the cases exhibited significantly higher frequency of the haplotypes CAG <or=19/GGN <or=21 (OR-5.2 at 95% CI-2.17-12.48, P < 0.001) and CAG <or=19/GGN > 21(OR-6.9 at 95%CI-2.85-17.01, P < 0.001) compared to the controls. No significant association was observed between GGN repeats and prostate-specific antigen levels and the age at diagnosis. Although a trend of short GGN repeats length in high-grade was observed, it was not significant (P = 0.09). Overall, our data reveals that specific GGN/CAG haplotypes (CAG <or=19/GGN <or=21 and CAG <or=19/GGN > 21) of AR gene increase the risk of prostate cancer and thus could serve as susceptibility marker for prostate cancer in South Indian men.

摘要

雄激素受体(AR)基因的GGN和CAG微卫星的种族差异表明它们在前列腺癌风险的显著种族差异中起作用。因此,我们进行了一项病例对照研究,以评估GGN重复单独或与CAG重复联合是否与南印度男性的前列腺癌风险相关。通过基因扫描分析确定的AR基因重复长度显示,与GGN重复数>21的男性相比,GGN重复数≤21的男性没有显著风险(95%置信区间为0.52-1.58时,比值比为0.91)。然而,当将我们早期研究中的CAG重复与GGN重复数据相结合时,与对照组相比,病例组中CAG≤19/GGN≤21(95%置信区间为2.17-12.48时,比值比为5.2,P<0.001)和CAG≤19/GGN>21(95%置信区间为2.85-17.01时,比值比为6.9,P<0.001)单倍型的频率显著更高。未观察到GGN重复与前列腺特异性抗原水平及诊断年龄之间存在显著关联。尽管在高级别病例中观察到GGN重复长度短的趋势,但不显著(P=0.09)。总体而言,我们的数据表明,AR基因的特定GGN/CAG单倍型(CAG≤19/GGN≤21和CAG≤19/GGN>21)会增加前列腺癌风险,因此可作为南印度男性前列腺癌的易感标志物。

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