Song Xiaoyu, Ru Meng, Steinsnyder Zoe, Tkachuk Kaitlyn, Kopp Ryan P, Sullivan John, Gümüş Zeynep H, Offit Kenneth, Joseph Vijai, Klein Robert J
Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Cancer Epidemiol Biomarkers Prev. 2022 Jul 1;31(7):1466-1472. doi: 10.1158/1055-9965.EPI-22-0053.
A previous genome-wide association study identified several loci with genetic variants associated with prostate cancer survival time in two cohorts from Sweden. Whether these variants have an effect in other populations or if their effect is homogenous across the course of disease is unknown.
These variants were genotyped in a cohort of 1,298 patients. Samples were linked with age, PSA level, Gleason score, cancer stage at surgery, and times from surgery to biochemical recurrence to death from prostate cancer. SNPs rs2702185 and rs73055188 were tested for association with prostate cancer-specific survival time using a multivariate Cox proportional hazard model. SNP rs2702185 was further tested for association with time to biochemical recurrence and time from biochemical recurrence to death with a multi-state model.
SNP rs2702185 at SMG7 was associated with prostate cancer-specific survival time, specifically the time from biochemical recurrence to prostate cancer death (HR, 2.5; 95% confidence interval, 1.4-4.5; P = 0.0014). Nine variants were in linkage disequilibrium (LD) with rs2702185; one, rs10737246, was found to be most likely to be functional based on LD patterns and overlap with open chromatin. Patterns of open chromatin and correlation with gene expression suggest that this SNP may affect expression of SMG7 in T cells.
The SNP rs2702185 at the SMG7 locus is associated with time from biochemical recurrence to prostate cancer death, and its LD partner rs10737246 is predicted to be functional.
These results suggest that future association studies of prostate cancer survival should consider various intervals over the course of disease.
之前的一项全基因组关联研究在来自瑞典的两个队列中确定了几个与前列腺癌生存时间相关的基因变异位点。这些变异在其他人群中是否有影响，或者它们在疾病过程中的影响是否一致尚不清楚。
在一个由1298名患者组成的队列中对这些变异进行基因分型。样本与年龄、前列腺特异性抗原（PSA）水平、 Gleason评分、手术时的癌症分期以及从手术到生化复发至前列腺癌死亡的时间相关联。使用多变量Cox比例风险模型测试单核苷酸多态性（SNP）rs2702185和rs73055188与前列腺癌特异性生存时间的相关性。使用多状态模型进一步测试SNP rs2702185与生化复发时间以及从生化复发到死亡时间的相关性。
SMG7基因上的SNP rs2702185与前列腺癌特异性生存时间相关，特别是从生化复发到前列腺癌死亡的时间（风险比，2.5；95%置信区间，1.4 - 4.5；P = 0.0014）。九个变异与rs2702185处于连锁不平衡（LD）状态；基于LD模式和与开放染色质的重叠，发现其中一个变异rs10737246最有可能具有功能。开放染色质模式和与基因表达的相关性表明，该SNP可能影响T细胞中SMG7的表达。
SMG7基因座上的SNP rs2702185与从生化复发到前列腺癌死亡的时间相关，并且其LD配对体rs10737246预计具有功能。
这些结果表明，未来前列腺癌生存的关联研究应考虑疾病过程中的不同时间间隔。
