Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence.
Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence.
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DOI：
10.1158/1078-0432.ccr-10-0881
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发表时间：
2011-03-01
期刊：
影响因子：
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通讯作者：
Hayes RB
中科院分区：
文献类型：
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作者：
Ahn J;Kibel AS;Park JY;Rebbeck TR;Rennert H;Stanford JL;Ostrander EA;Chanock S;Wang MH;Mittal RD;Isaacs WB;Platz EA;Hayes RB
全基因组关联研究（GWAS）已经确定了多个新的前列腺癌易感基因座。这些常见的遗传变异是否与偶发转移性前列腺癌或临床局限性前列腺癌手术治疗后复发相关尚不确定。根据癌症易感性遗传标记（CGEMS）中与前列腺癌的全基因组关联，选择12个SNP用于与前列腺转移癌和复发相关的研究。为了评估转移性疾病的风险，我们在3项病例对照研究中，通过逻辑回归对470例偶发转移性前列腺癌病例和1945例对照进行了12个SNP的基因型比较。为了评估这些SNPs与前列腺癌复发风险的关系，我们对1412名接受局限性前列腺癌治疗的男性进行了考克斯回归分析，其中包括328名复发患者，并在病例-病例研究中使用了逻辑回归分析，比较了450例复发和450例非复发前列腺癌病例。采用荟萃分析和逆方差权重总结了转移性疾病和复发风险的研究特异性RR。MSMB rs 10993994（每个变异等位基因汇总RR=1.24，95% CI=1.05-1.48）、8 q24 rs 4242382（RR=1.40，95% CI=1.13-1.75）和8 q24 rs6983267（RR=0.67，95% CI=0.50-0.89）与转移性前列腺癌风险相关。12个SNPs中没有一个与前列腺癌复发相关。MSMB和8 q24中的SNP总体上易患前列腺癌，与转移性前列腺癌的风险相关，转移性前列腺癌是这种疾病的最致命形式。在易感性SNP中，未发现预测前列腺癌复发的SNP。特异于这两种表型的GWAS可能会识别其他表型特异性遗传决定因素。
Genome-wide association studies (GWAS) have identified multiple novel prostate cancer predisposition loci. Whether these common genetic variants are associated with incident metastatic prostate cancer or with recurrence after surgical treatment for clinically localized prostate cancer is uncertain. Twelve SNPs were selected for study in relation to prostate metastatic cancer and recurrence, based on their genome-wide association with prostate cancer in the Cancer Genetic Markers of Susceptibility (CGEMS). To assess risk for metastatic disease, we compared genotypes for the 12 SNPs by logistic regression of 470 incident metastatic prostate cancer cases and 1945 controls in 3 case-control studies. To assess the relationship of these SNPs to risk for prostate cancer recurrence, we used Cox regression in a cohort of 1412 men treated for localized prostate cancer, including 328 recurrences, and used logistic regression in a case-case study, comparing 450 recurrent versus 450 nonrecurrent prostate cancer cases. Study-specific RRs for risk of metastatic disease and recurrence were summarized using meta-analysis, with inverse variance weights. MSMB rs10993994 (per variant allele summary RR=1.24, 95% CI=1.05-1.48), 8q24 rs4242382 (RR=1.40, 95% CI=1.13-1.75) and 8q24 rs6983267 (RR=0.67, 95% CI=0.50-0.89) were associated with risk for metastatic prostate cancer. None of the 12 SNPs was associated with prostate cancer recurrence. SNPs in MSMB and 8q24 which predispose to prostate cancer overall are associated with risk for metastatic prostate cancer, the most lethal form of this disease. SNPs predictive of prostate cancer recurrence were not identified, among the predisposition SNPs. GWAS specific to these two phenotypes may identify additional phenotype-specific genetic determinants.