Division of Integrated Cancer Genomics, Translational Genomics Research Institute, Phoenix, Arizona, United States of America.
PLoS One. 2011;6(5):e19494. doi: 10.1371/journal.pone.0019494. Epub 2011 May 16.
The EphB2 gene has been implicated as a tumor suppressor gene somatically altered in both prostate cancer (PC) and colorectal cancer. We have previously shown an association between an EphB2 germline nonsense variant and risk of familial prostate cancer among African American Men (AAM). Here we set out to test the hypothesis that common variation within the EphB2 locus is associated with increased risk of sporadic PC in AAM. We genotyped a set of 341 single nucleotide polymorphisms (SNPs) encompassing the EphB2 locus, including known and novel coding and noncoding variants, in 490 AA sporadic PC cases and 567 matched controls. Single marker-based logistical regression analyses revealed seven EphB2 SNPs showing statistically significant association with prostate cancer risk in our population. The most significant association was achieved for a novel synonymous coding SNP, TGen-624, (Odds Ratio (OR) = 0.22; 95% Confidence Interval (CI) 0.08-0.66, p = 1×10(-5)). Two other SNPs also show significant associations toward a protective effect rs10465543 and rs12090415 (p = 1×10(-4)), OR = 0.49 and 0.7, respectively. Two additional SNPs revealed trends towards an increase in risk of prostate cancer, rs4612601 and rs4263970 (p = 0.001), OR = 1.35 and 1.31, respectively. Furthermore, haplotype analysis revealed low levels of linkage disequilibrium within the region, with two blocks being associated with prostate cancer risk among our population. These data suggest that genetic variation at the EphB2 locus may increase risk of sporadic PC among AAM.
EphB2 基因已被证实是一种肿瘤抑制基因，在前列腺癌 (PC) 和结直肠癌中发生体细胞改变。我们之前已经证明 EphB2 种系无义变异与非裔美国男性 (AAM) 家族性前列腺癌的风险之间存在关联。在这里，我们着手检验 EphB2 基因座内常见变异是否与 AAM 中散发型 PC 风险增加相关的假设。我们在 490 例 AA 散发型 PC 病例和 567 例匹配对照中，对 EphB2 基因座内的一组 341 个单核苷酸多态性 (SNP) 进行了基因分型，包括已知和新的编码和非编码变异。基于单标记的逻辑回归分析显示，EphB2 中的 7 个 SNPs 与我们人群中的前列腺癌风险具有统计学意义的关联。最显著的关联是一个新的同义编码 SNP，TGen-624(rs10465543 和 rs12090415)，OR=0.49 和 0.7，分别为 0.22；95%置信区间 (CI) 0.08-0.66，p=1×10(-5))。另外两个 SNPs 也显示出向保护性作用 rs10465543 和 rs12090415 靠拢的显著关联 (p=1×10(-4))，OR=0.49 和 0.7。另外两个 SNPs 显示出增加前列腺癌风险的趋势，rs4612601 和 rs4263970(p=0.001)，OR=1.35 和 1.31。此外，单体型分析显示该区域内的连锁不平衡程度较低，两个块与我们人群中的前列腺癌风险相关。这些数据表明 EphB2 基因座的遗传变异可能会增加 AAM 中散发型 PC 的风险。
