Prostate cancer (PCa) risk variants and risk of fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.
Prostate cancer (PCa) risk variants and risk of fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.
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DOI：
10.1016/j.eururo.2013.12.058
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发表时间：
2014-06
期刊：
影响因子：
23.4
通讯作者：
Kraft, Peter
中科院分区：
文献类型：
--
作者：
Shui, Irene M.;Lindstroem, Sara;Kibel, Adam S.;Berndt, Sonja I.;Campa, Daniele;Gerke, Travis;Penney, Kathryn L.;Albanes, Demetrius;Berg, Christine;Bueno-de-Mesquita, H. Bas;Chanock, Stephen;Crawford, E. David;Diver, W. Ryan;Gapstur, Susan M.;Gaziano, J. Michael;Giles, Graham G.;Henderson, Brian;Hoover, Robert;Johansson, Mattias;Le Marchand, Loic;Ma, Jing;Navarro, Carmen;Overvad, Kim;Schumacher, Fredrick R.;Severi, Gianluca;Siddiq, Afshan;Stampfer, Meir;Stevens, Victoria L.;Travis, Ruth C.;Trichopoulos, Dimitrios;Vineis, Paolo;Mucci, Lorelei A.;Yeager, Meredith;Giovannucci, Edward;Kraft, Peter
关键词：
前列腺癌（PCa）的筛查和诊断受到无法预测谁有可能发展为致命疾病以及谁患有惰性癌症的阻碍。研究已经确定了PCa发病率的多个遗传风险位点，但尚不清楚它们是否可用作PCa特异性死亡率（PCSM）的生物标志物。研究47个已确定的PCa风险单核苷酸多态性（SNPs）与PCSM的关联。我们纳入了10487名前列腺癌患者和11024名对照者，中位随访时间为8.3年，在此期间发生了1053例前列腺癌死亡。主要结局为PCSM。在文献中，风险等位基因被定义为与PCa风险增加相关的等位基因。我们使用考克斯比例风险回归来计算每个SNP的风险比与诊断后进展到PCSM的时间。我们还使用逻辑回归来计算每个风险SNP的比值比，将致命的PCa病例与对照进行比较。在这些病例中，我们发现47个SNPs中的8个与PCSM的时间显著相关（p < 0.05）。rs11672691的危险等位基因（基因间）与PCSM风险增加相关，而7个SNPs的风险等位基因与PCSM风险呈负相关。（rs13385191 [C2orf43]，rs17021918 [PDLIM5]，rs10486567 [JAZF 1]，rs6465657 [LMTK2]，rs7127900（基因间），rs2735839 [KLK 3]，rs10993994 [MSMB]，rs13385191 [C2orf43]）。在病例对照分析中，22个SNP与致命性PCa的风险相关（p < 0.05），但大多数不能区分致命性和非致命性PCa。Rs11672691和rs10993994与致死性和非致死性PCa均相关，而rs6465657、rs7127900、rs2735839和rs13385191仅与非致死性PCa相关。8个已确定的风险位点与诊断后进展为PCSM相关。22个SNP与致死性PCa发生率相关，但大多数不能区分致死性和非致死性PCa。相对较小的关联程度并不能很好地转化为风险预测，但这些发现值得进一步随访，因为它们可能会产生有关致命PCa复杂生物学的重要线索。患者总结：在本报告中，我们评估了已确定的PCa风险变异是否可以预测PCSM。我们发现了八个与PCSM相关的风险变量：一个预测PCSM风险增加，而七个与风险降低相关。需要更大规模的研究，重点是致命的PCa，以确定更多的标志物，可以帮助预测。
Screening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM). To examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM. We included 10 487 men who had PCa and 11 024 controls, with a median follow-up of 8.3 yr, during which 1053 PCa deaths occurred. The main outcome was PCSM. The risk allele was defined as the allele associated with an increased risk for PCa in the literature. We used Cox proportional hazards regression to calculate the hazard ratios of each SNP with time to progression to PCSM after diagnosis. We also used logistic regression to calculate odds ratios for each risk SNP, comparing fatal PCa cases to controls. Among the cases, we found that 8 of the 47 SNPs were significantly associated (p < 0.05) with time to PCSM. The risk allele of rs11672691 (intergenic) was associated with an increased risk for PCSM, while 7 SNPs had risk alleles inversely associated (rs13385191 [C2orf43], rs17021918 [PDLIM5], rs10486567 [JAZF1], rs6465657 [LMTK2], rs7127900 (intergenic), rs2735839 [KLK3], rs10993994 [MSMB], rs13385191 [C2orf43]). In the case-control analysis, 22 SNPs were associated (p < 0.05) with the risk of fatal PCa, but most did not differentiate between fatal and nonfatal PCa. Rs11672691 and rs10993994 were associated with both fatal and nonfatal PCa, while rs6465657, rs7127900, rs2735839, and rs13385191 were associated with nonfatal PCa only. Eight established risk loci were associated with progression to PCSM after diagnosis. Twenty-two SNPs were associated with fatal PCa incidence, but most did not differentiate between fatal and nonfatal PCa. The relatively small magnitudes of the associations do not translate well into risk prediction, but these findings merit further follow-up, because they may yield important clues about the complex biology of fatal PCa. Patient summary: In this report, we assessed whether established PCa risk variants could predict PCSM. We found eight risk variants associated with PCSM: One predicted an increased risk of PCSM, while seven were associated with decreased risk. Larger studies that focus on fatal PCa are needed to identify more markers that could aid prediction.
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通讯作者：
Easton, Douglas F.
影响因子：
3.7
作者：
Lindstrom S;Schumacher F;Siddiq A;Travis RC;Campa D;Berndt SI;Diver WR;Severi G;Allen N;Andriole G;Bueno-de-Mesquita B;Chanock SJ;Crawford D;Gaziano JM;Giles GG;Giovannucci E;Guo C;Haiman CA;Hayes RB;Halkjaer J;Hunter DJ;Johansson M;Kaaks R;Kolonel LN;Navarro C;Riboli E;Sacerdote C;Stampfer M;Stram DO;Thun MJ;Trichopoulos D;Virtamo J;Weinstein SJ;Yeager M;Henderson B;Ma J;Le Marchand L;Albanes D;Kraft P
通讯作者：
Kraft P