A novel prostate cancer susceptibility locus at 19q13.
A novel prostate cancer susceptibility locus at 19q13.
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DOI：
10.1158/0008-5472.can-08-3347
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发表时间：
2009-04-01
期刊：
影响因子：
11.2
通讯作者：
Zheng SL
中科院分区：
文献类型：
--
作者：
Hsu FC;Sun J;Wiklund F;Isaacs SD;Wiley KE;Purcell LD;Gao Z;Stattin P;Zhu Y;Kim ST;Zhang Z;Liu W;Chang BL;Walsh PC;Duggan D;Carpten JD;Isaacs WB;Grönberg H;Xu J;Zheng SL
一项针对癌症易感性遗传标记(CGEMS)倡议的两阶段全基因组关联研究发现，基因组中150个区域的SNP可能与前列腺癌(PCa)风险相关。我们对这些结果进行了筛选，确定了43个独立的单核苷酸多态(SNPs)，其中在五个CGEMS研究人群中，病例组的风险等位基因频率始终高于对照组。这43个SNPs中有22个的基因信息是直接通过基因分型或间接归因于我们从瑞典人群为基础的病例对照研究(CAPS)中选择的500例病例和500名对照。这22个SNP中有两个与前列腺癌风险显著相关(P<；0.05)。然后我们对其余病例(N=2,393)和对照组(N=1,222)的这两个SNP进行了基因分型，发现19q13的rs887391与前列腺癌的风险高度相关(P=9.4×10−4)。在约翰霍普金斯医院的一项病例对照研究中也发现了这种SNP的相似关联趋势，尽管结果在统计学上并不显著。总体而言，在所研究的七个研究人群中，rs887391的风险等位基因的频率在病例中始终高于对照，综合等位基因测试的总体P=3.2x10−7。在19q13在CAPS和JHH研究人群中的110kb区域的精细定位研究表明，rs887391是该地区关联最强的SNP。有必要对这一地区进行更多的确认研究。
A two-stage genome-wide association study (GWAS) of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative identified SNPs in 150 regions across the genome that may be associated with prostate cancer (PCa) risk. We filtered these results to identify 43 independent single nucleotide polymorphisms (SNPs) where the frequency of the risk allele was consistently higher in cases than in controls in each of the five CGEMS study populations. Genotype information for 22 of these 43 SNPs was obtained either directly by genotyping or indirectly by imputation in our PCa GWAS of 500 cases and 500 controls selected from a population-based case-control study in Sweden (CAPS). Two of these 22 SNPs were significantly associated with PCa risk (P<0.05). We then genotyped these two SNPs in the remaining cases (N=2,393) and controls (N=1,222) from CAPS and found rs887391 at 19q13 was highly associated with PCa risk (P=9.4 × 10−4). A similar trend of association was found for this SNP in a case-control study from Johns Hopkins Hospital, albeit the result was not statistically significant. Altogether, the frequency of the risk allele of rs887391 was consistently higher in cases than controls among each of seven study populations examined, with an overall P=3.2 × 10−7 from a combined allelic test. A fine mapping study in a 110 Kb region at 19q13 among CAPS and JHH study populations revealed rs887391 was the most strongly associated SNP in the region. Additional confirmation studies of this region are warranted.