Platz E A, Giovannucci E, Dahl D M, Krithivas K, Hennekens C H, Brown M, Stampfer M J, Kantoff P W
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Cancer Epidemiol Biomarkers Prev. 1998 May;7(5):379-84.
The androgen receptor (AR) gene contains a polymorphic GGN microsatellite in exon 1, which encodes polyglycine in the amino terminus of the AR. Previous work has shown that a polymorphic region of CAG repeats also in exon 1 is inversely related to the ability of the AR to transactivate other genes and to prostate cancer risk. We investigated whether AR gene GGN repeat length is related to prostate cancer in a nested study of 582 cases and 794 controls matched on age and smoking status in the Physicians' Health Study. DNA was prepared from archived blood. Using PCR, the region surrounding the GGN repeat was amplified. Fluorescence-labeled primers were used such that the fragment produced could be sized using polyacrylamide gels and Genescan software. We estimated odds ratios and 95% confidence intervals from logistic models controlling for the matching variables for the relation between GGN repeat length and total prostate cancer and by stage/grade and by age at diagnosis. Among controls, the most frequent GGN repeat lengths were 23 (53.5%) and 24 (34.0%), with a range of 10-29. There was no statistically significant difference in the mean GGN repeat length between cases (23.13) and controls (23.05). However, cases had a narrower spread of repeats lengths (parametric test, P = 0.03; nonparametric test, P = 0.07) than controls, with fewer extreme lengths in either direction. The risk of total prostate cancer was slightly increased for a GGN repeat length of 23 compared to all others (odds ratio, 1.20; 95% confidence interval 0.97-1.49); risk did not vary by tumor stage/grade. For every one repeat deviation in either direction from 23, the risk of prostate cancer decreased by 8% (P = 0.04). Although the AR gene GGN repeat probably plays only a modest role in prostate cancer, the observed relation of this repeat with prostate cancer risk supports the evaluation of the effect of GGN repeat length on AR transactivation.
雄激素受体（AR）基因的第1外显子含有一个多态性的GGN微卫星序列，该序列在AR的氨基末端编码多聚甘氨酸。先前的研究表明，同样位于第1外显子的CAG重复多态性区域与AR激活其他基因的能力以及前列腺癌风险呈负相关。在医师健康研究中，我们进行了一项巢式研究，纳入582例病例和794例年龄及吸烟状况相匹配的对照，调查AR基因GGN重复长度是否与前列腺癌相关。从存档血液中提取DNA。采用PCR扩增GGN重复序列周围区域。使用荧光标记引物，以便通过聚丙烯酰胺凝胶和基因扫描软件确定所产生片段的大小。我们通过逻辑模型估计优势比和95%置信区间，该模型控制了匹配变量，以研究GGN重复长度与总前列腺癌之间的关系，并按肿瘤分期/分级以及诊断时的年龄进行分析。在对照组中，最常见的GGN重复长度为23（53.5%）和24（34.0%），范围为10 - 29。病例组（23.13）和对照组（23.05）的平均GGN重复长度无统计学显著差异。然而，病例组重复长度的分布范围比对照组窄（参数检验，P = 0.03；非参数检验，P = 0.07），两端的极端长度较少。与其他所有长度相比，GGN重复长度为23时，总前列腺癌风险略有增加（优势比，1.20；95%置信区间0.97 - 1.49）；风险在肿瘤分期/分级上无差异。从23开始，每向任一方向偏离一个重复，前列腺癌风险降低8%（P = 0.04）。尽管AR基因GGN重复序列可能仅在前列腺癌中起适度作用，但观察到的该重复序列与前列腺癌风险的关系支持评估GGN重复长度对AR转录激活的影响。
