雄激素受体基因微卫星多态性与前列腺癌的生物学行为

The Polymorphism of CAG Microsatellite in the Androgen Receptor Gene and the Biological Behavior of Prostate Cancer

目的 探讨雄激素受体 (AR)基因CAG微卫星多态性与前列腺癌 (PC)生物学行为的关系。方法 采用聚合酶链反应 单链构象多态性分析法 (PCR SSCP) ,对 37例中国人、5 7例美国白人以及 1 9例美国黑人PC患者共 1 1 3例PC标本 ,行AR基因CAG微卫星数量测定 ,并进行不同病理期别、细胞分化级别以及种族间的比较。结果 PC病变C期和D期的AR基因CAG数量均少于B期 ,其均数分别为 :中国人 2 2 .1 4± 2 .6 4与 2 5 .0 4± 1 .88(P <0 .0 1 )、美国白人 2 1 .97± 3.31与 2 3.74± 2 .49(P <0 .0 5 )、美国黑人 1 9.46± 3.1 4与 2 1 .75± 1 .1 0 (P <0 .0 5 ) ,差异显著。短的AR基因CAG (数量 <2 2 )的分布分别是 :中国人B期病变占1 3.0 % (3/2 3)、C～D期 2 8.6 % (4/1 4) ,美国白人B期 1 4.8% (4/2 7)、C～D期 36 .7% (1 1 /30 ) ,美国黑人B期 2 5 .0 % (1 /4 )、C～D期 80 .0 % (1 2 /1 5 ) ;其长的AR基因CAG(数量≥ 2 2 )的分布比例与之相反 ,差异显著 (P <0 .0 5 )。AR基因CAG数量随着肿瘤细胞分化程度的降低而减少 ,在高、中、低分化PC中其均数分别为 :中国人 2 5 .6 0± 1 .6 7、2 4.2 9± 3.45、2 3.6 4± 2 .5 6 ;美国白人 2 3.81± 2 .81、2 3.1 1± 1 .79、2 1 .44± 4.0 3;美国黑人 2 1 .0 0± 0 .0

Objective To explore the relationship between the CAG microsatellite in androgen receptor(AR)gene and the biological behavior of prostate cancer(PC).Methods The number of CAG repeats in exon 1 of the AR gene was measured in 113 PC tissues by polymerase chain reaction single strand conformation polymophism(PCR SSCP)analysis.The number of CAG repeats was tested to determine its association with stages and grades of PC among the three races.Results The average number of CAG repeats was statistically different between stage B and stage C～D in Chinese 25.04±1.88 and 22.14±2.64( P <0.01),in the non Hispanic white 23.74±2.49 and 21.97±3.31( P <0.05),in African American patients 21.75±1.10 and 19.46±3.14( P <0.05).The short CAG(<22) was differently distributed to the stage B and stage C～D: 13.0%(3/23) and 28.6%(4/14) in Chinese( P <0.05), 14.8% (4/27)and 36.7%(11/30)in non Hispanic white( P <0.05),25.0%(1/4)and 80.0%(12/15)in African American patients( P <0.05).The averages CAG repeat number increase along with in low,middle and high differentiation of tumor tissues:23.64± 2.56 ,24.29±3.45,25.6±1.67 in Chinese;21.44±4.03,23.11±1.79,23.81±2.81 in non Hispanic Whit;19.57±2.56,21.33±0.47,21.00±0.00 in African American patients.The distributions of short CAG dropped with in low,middle and high differentiation of PC:60.0%(15/25),28.6%(2/7),0%(0/5)in Chinese;50.0%(9/18),22.2%(4/18),14.3%(3/21)in non Hispanic Whit;71.4%(10/14),33.3%(1/3),0%(0/2)in African American patients.The difference between in high and low differentiation of PC is significant among the three races( P <0.05).The stage C～D and low differentiation of PC were more in African American(78.9% and 73.7%)than in non Hispanic Whit patients(52.6% and 31.6%) and the averages of CAG repeat number were less in African American(19.89±2.95)than in non Hispanic Whit patients(22.95±2.97).Conclusion The number of CAG in AR gene may be a factor of the makeup feature of PC in biology and the PC that contains short CAG in AR presents high aggression.