German Cancer Research Center-DKFZ, Heidelberg, Germany.
PLoS One. 2011;6(11):e27921. doi: 10.1371/journal.pone.0027921. Epub 2011 Nov 18.
Pancreatic cancer has one of the worst mortality rates of all cancers. Little is known about its etiology, particularly regarding inherited risk. The PanScan project, a genome-wide association study, identified several common polymorphisms affecting pancreatic cancer susceptibility. Single nucleotide polymorphisms (SNPs) in ABO, sonic hedgehog (SHH), telomerase reverse transcriptase (TERT), nuclear receptor subfamily 5, group A, member 2 (NR5A2) were found to be associated with pancreatic cancer risk. Moreover the scan identified loci on chromosomes 13q22.1 and 15q14, to which no known genes or other functional elements are mapped. We sought to replicate these observations in two additional, independent populations (from Germany and the UK), and also evaluate the possible impact of these SNPs on patient survival. We genotyped 15 SNPs in 690 cases of pancreatic ductal adenocarcinoma (PDAC) and in 1277 healthy controls. We replicated several associations between SNPs and PDAC risk. Furthermore we found that SNP rs8028529 was weakly associated with a better overall survival (OS) in both populations. We have also found that NR5A2 rs12029406_T allele was associated with a shorter survival in the German population. In conclusion, we found that rs8028529 could be, if these results are replicated, a promising marker for both risk and prognosis for this lethal disease.
胰腺癌的死亡率在所有癌症中是最高的之一。目前人们对其病因学知之甚少，尤其是遗传性风险。PanScan 项目是一项全基因组关联研究，确定了几个影响胰腺癌易感性的常见多态性。ABO、sonic hedgehog (SHH)、端粒酶逆转录酶 (TERT)、核受体亚家族 5 组 A 成员 2 (NR5A2) 的单核苷酸多态性 (SNP) 与胰腺癌风险相关。此外，该扫描还确定了染色体 13q22.1 和 15q14 上的基因座，这些基因座没有已知的基因或其他功能元件映射。我们试图在另外两个独立的人群（来自德国和英国）中复制这些观察结果，并评估这些 SNP 对患者生存的可能影响。我们对 690 例胰腺导管腺癌 (PDAC) 病例和 1277 例健康对照进行了 15 个 SNP 的基因分型。我们复制了几个 SNP 与 PDAC 风险之间的关联。此外，我们发现 SNP rs8028529 与两个群体的总生存 (OS) 呈弱相关。我们还发现 NR5A2 rs12029406_T 等位基因与德国人群的生存时间较短有关。总之，如果这些结果得到复制，我们发现 rs8028529 可能是这种致命疾病的风险和预后的有前途的标志物。
