A Replication Study Examining Novel Common Single Nucleotide Polymorphisms Identified Through a Prostate Cancer Genome-wide Association Study in a Japanese Population
A Replication Study Examining Novel Common Single Nucleotide Polymorphisms Identified Through a Prostate Cancer Genome-wide Association Study in a Japanese Population
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DOI：
10.1093/aje/kwr271
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发表时间：
2011-12-15
影响因子：
5
通讯作者：
Spurdle, Amanda B.
中科院分区：
文献类型：
--
作者：
Batra, Jyotsna;Lose, Felicity;Spurdle, Amanda B.
在最近的日本人全基因组关联研究（GWAS）中鉴定了五个新的前列腺癌风险基因座（Takata et al.，纳特·吉内特2010; 42（9）：751 - 754）。这些作者提出，除了群体特异性连锁不平衡模式，GWAS单核苷酸多态性（SNP）优先级和/或研究设计的局限性可以解释以前在高加索人中进行的GWAS中缺乏这些位点的鉴定。因此，作者在1，357名前列腺癌患者和1，403名欧洲血统的健康澳大利亚男性中进行了重复研究（2004 - 2008）。发现5p15处的rs12653946 SNP与前列腺癌风险显著相关（比值比= 1.20，95%置信区间：1.07，1.34; P = 0.002）。根据连锁不平衡计算，rs12653946 SNP代表一个独立的基因座，与先前鉴定的TERT-CLPTM1L癌症关联区域不同。此外，AceView的分析（Thierry-Mieg和Thierry-Mieg，Genome Biol.2006; 7（增刊1）：S12）表明，rs 12653946位于睾丸表达基因的内含子内，强烈预测该基因将翻译一种名为tojy.aApr07的概念性8.1千道尔顿蛋白质。福尔斯。作者的研究结果表明，为了突出实验研究的风险相关位点，并纳入未来前列腺癌的风险预测模型，有必要对明显的种族特异性风险关联进行随访。
Five novel prostate cancer risk loci were identified in a recent genome-wide association study (GWAS) of Japanese persons (Takata et al., Nat Genet. 2010;42(9):751-754). Those authors proposed that apart from population-specific linkage disequilibrium patterns, limitations of GWAS single nucleotide polymorphism (SNP) prioritization and/or study design could explain the lack of identification of these loci in GWAS previously conducted among Caucasians. Thus, the authors undertook a replication study in 1,357 prostate cancer patients and 1,403 healthy Australian males of European descent (2004-2008). The rs12653946 SNP at 5p15 was found to be significantly associated with prostate cancer risk (odds ratio = 1.20, 95% confidence interval: 1.07, 1.34; P = 0.002). On the basis of linkage disequilibrium calculations, the rs12653946 SNP represents an independent locus, distinct from the previously identified TERT-CLPTM1L cancer nexus region. Further, analysis from AceView (Thierry-Mieg and Thierry-Mieg, Genome Biol. 2006;7(suppl 1):S12) indicated that rs12653946 falls within the intron of a testis-expressed gene strongly predicted to translate a conceptual 8.1-kilodalton protein named tojy.aApr07. The authors' findings suggest that follow-up of apparently ethnicity-specific risk associations are warranted in order to highlight risk-associated loci for experimental studies and for incorporation into future risk prediction models for prostate cancer.