Sun Jielin, Purcell Lina, Gao Zhengrong, Isaacs Sarah D, Wiley Kathleen E, Hsu Fang-Chi, Liu Wennuan, Duggan David, Carpten John D, Grönberg Henrik, Xu Jianfeng, Chang Bao-Li, Partin Alan W, Walsh Patrick C, Isaacs William B, Zheng S Lilly
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Prostate. 2008 May 15;68(7):691-7. doi: 10.1002/pros.20754.
Three SNPs at 17q12 and four SNPs at 17q24.3 were recently identified to be associated with prostate cancer risk using a genome-wide association study.
We evaluated these 7 SNPs in two hospital-based case-control study populations, including European Americans (EA; 1,563 cases and 576 controls) and African Americans (AA; 364 cases and 353 controls).
Each of the reported risk alleles of these seven SNPs were more common in cases than in controls among EA and AA. The differences were highly significant in EA (P = 10(-4)) and marginally significant in AA (P = 0.04) for SNPs at 17q12. In contrast, the differences were not statistically significant in EA or AA for SNPs at 17q24.3, but were marginally significant for two SNPs (P = 0.04-0.06) when EA and AA subjects were combined. Similar results were obtained when genotype and haplotype frequencies between cases and controls were analyzed. These risk variants were not associated with more aggressive prostate cancer or other clinical variables such as TNM stage, pre-operative PSA, or age at diagnosis.
Results from our study provide the first confirmation of these 17q SNPs as novel prostate cancer susceptibility loci in EA and the first indication that these two loci may also play roles in prostate cancer risk among AA.
最近通过全基因组关联研究确定,17q12处的三个单核苷酸多态性(SNP)和17q24.3处的四个SNP与前列腺癌风险相关。
我们在两项基于医院的病例对照研究人群中评估了这7个SNP,包括欧裔美国人(EA;1563例病例和576例对照)和非裔美国人(AA;364例病例和353例对照)。
在EA和AA中,这七个SNP的每个已报道风险等位基因在病例中比在对照中更常见。对于17q12处的SNP,在EA中差异高度显著(P = 10⁻⁴),在AA中差异边缘显著(P = 0.04)。相比之下,对于17q24.3处的SNP,在EA或AA中差异无统计学意义,但在合并EA和AA受试者时,两个SNP差异边缘显著(P = 0.04 - 0.06)。分析病例和对照之间的基因型和单倍型频率时也获得了类似结果。这些风险变异与侵袭性更强的前列腺癌或其他临床变量如TNM分期、术前前列腺特异抗原(PSA)或诊断年龄无关。
我们的研究结果首次证实这些17q的SNP是EA中新的前列腺癌易感位点,并且首次表明这两个位点在AA的前列腺癌风险中也可能起作用。