Genetic prostate cancer risk assessment: common variants in 9 genomic regions are associated with cumulative risk.
Genetic prostate cancer risk assessment: common variants in 9 genomic regions are associated with cumulative risk.
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DOI：
10.1016/j.juro.2010.04.032
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发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Catalona WJ
中科院分区：
文献类型：
--
作者：
Helfand BT;Fought AJ;Loeb S;Meeks JJ;Kan D;Catalona WJ
染色体8q24和17q上的五个遗传变异先前被证明与前列腺癌(CAP)风险有累积关联。我们的研究小组之前已经证明了这些变异与临床病理特征之间的关联。最近，在染色体2p15、10q11、11q13和Xp11上又发现了4个CAP易感变异。我们的目标是检查包含所有9个遗传变异的累积风险评估，并确定新变异与临床病理肿瘤特征的关系。对687名接受根治性前列腺切除术(2002-2008)的欧洲血统男性和777名健康志愿者对照进行了所有9个变异体的基因检测。我们比较了CAP病例和对照组中这些变异的频率，并检验了累积模型。此外，我们还确定了4个新变异体的携带者状态与临床和病理肿瘤特征的关系。与对照组相比，CAP病例所有9个风险变量的出现频率都增加了。包括9个SNPs的累积模型比仅限于最初描述的5个SNPs的模型提供了更大的上限风险分层。具体地说，携带≥6基因变异的男性患CAP的风险增加了6倍。虽然2p15和11q13携带者更有可能具有侵袭性特征，但其他临床病理特征在携带者和非携带者之间相似。位于9个区域的遗传变异与CAP风险有累积关联。识别越来越多的SNP可能会更好地理解它们与CAP风险和疾病侵袭性的组合关系。
Five genetic variants along chromosomes 8q24 and 17q were previously shown to have a cumulative association with prostate cancer (CaP) risk. Our research group has previously demonstrated an association between these variants and clincopathologic characteristics. More recently, 4 additional CaP susceptibility variants were identified on chromosomes 2p15, 10q11, 11q13 and Xp11. Our objectives were to examine a cumulative risk assessment incorporating all 9 genetic variants, and to determine the relationship of the new variants with clincopathologic tumor features. The genotype for all 9 variants was determined in 687 men of European ancestry who underwent radical prostatectomy (2002-2008) and 777 healthy volunteer controls. We compared the frequencies of these variants between CaP cases and controls and examined a cumulative model. In addition, we determined the relationship between carrier status for the 4 new variants and clinical and pathology tumor features. CaP cases had an increased frequency of all 9 risk variants compared to controls. A cumulative model that included the 9 SNPs provided greater CaP risk stratification than a model restricted to the original 5 SNPs described. Specifically, men with ≥6 variants had a >6-fold increased risk of CaP. Although 2p15 and 11q13 carriers were more likely to have aggressive features, other clinical-pathology features were similar between carriers and non-carriers. Genetic variants located in 9 regions have a cumulative association with CaP risk. The identification of an increasing number of SNPs may provide a greater understanding of their combined relationship with CaP risk and disease aggressiveness.
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影响因子：
11.2
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
通讯作者：
Zheng SL
影响因子：
3.5
作者：
Chang, Bao-Li;Cramer, Scott D.;Xu, Jianfeng
通讯作者：
Xu, Jianfeng
影响因子：
2.8
作者：
Sun, Jielin;Chang, Bao-Li;Isaacs, Sarah D.;Wiley, Kathleen E.;Wiklund, Fredrik;Stattin, Par;Duggan, David;Carpten, John D.;Trock, Bruce J.;Partin, Alan W.;Walsh, Patrick C.;Gronberg, Henrik;Xu, Jianfeng;Isaacs, William B.;Zheng, S. Lilly
通讯作者：
Zheng, S. Lilly
影响因子：
30.8
作者：
Haiman, Christopher A.;Patterson, Nick;Reich, David
通讯作者：
Reich, David
DOI：
10.1073/pnas.0914061107
发表时间：
2010-02-02
影响因子：
11.1
作者：
Xu, Jianfeng;Zheng, Siqun Lilly;Isaacs, William B.
通讯作者：
Isaacs, William B.