雄激素受体基因第一外显子CAG重复序列长度多态性与男性膀胱癌的发生有关

Length of CAG repeat at exon 1 of androgen receptor gene is associated to development of bladder carcinoma in males

目的:探讨人雄激素受体(AR)基因第一外显子CAG串联短重复序列(STR)多态性与男性膀胱癌发生之间的关系. 方法: 石蜡包埋的男性膀胱癌标本进行基因组DNA提取,PCR扩增,变性聚丙烯酰胺凝胶电泳,经银染显示单股DNA链片段长度. 根据标本的泳动度推算CAG STR的n值;选取代表性的标本产物直接测序,验证上述检测的准确性. 以男性阑尾炎标本作为参照组. 结果: 95例膀胱癌标本中有6例(6.3%)出现微卫星不稳定(MSI)现象,其中1例因正常组织过少而无法确定其产物的正常泳动位置,不做以下分析. 94例膀胱癌及相同例数参照标本的CAG STR n值范围分别为8～26和14～30,均数分别为20.07±3.12和21.06±3.39,两者有统计学意义(P<0.05). 结论: AR基因第一外显子CAG STR与男性膀胱癌的发生或(和)发展有关,CAG STR较短的男性个体患膀胱癌的危险性可能增加.

AIM： To study the possible association between the length of the polymorphic CAG short tandem repeat （STR） at androgen receptor （AR） first exon and bladder cancer development. METHODS： Genomic DNA was extracted from the paraffin-embedded bladder carcinoma tissues from male patients and amplified by PCR and then the products were resolved by electrophoresis on denaturing polyacrylamide gels and visualized through silver staining. The CAG repeat numbers were assessed by the mobility of their products and direct sequencing for some representa- tive samples. The samples with appendicitis from 94 male patients were examined in a parallel way as a reference group. RESULTS： A total number of 95 of bladder cancer samples were examined. Six of them （6.3%） showed microsatellite instability, with one excluded from the following assessment due to the difficulty in determining precisely the normal position of its amplification product. The CAG repeat numbers for the 94 patients with bladder cancer and the reference patients with appendicitis were 8 -26 （20.07 ± 3.12） and 14 - 30 （21.06 ± 3.39）, respectively, with statistically significant difference. CONCLUSION： CAG STR at the first exon of AR gene is associated to the development and/or progression of bladder carcinoma in male patients. A shorter CAG STR at the locus may predispose the male individ-uals to the development of bladder cancer.