TY - JOUR
T1 - SNPs at SMG7 Associated with Time from Biochemical Recurrence to Prostate Cancer Death
AU - Song, Xiaoyu
AU - Ru, Meng
AU - Steinsnyder, Zoe
AU - Tkachuk, Kaitlyn
AU - Kopp, Ryan P.
AU - Sullivan, John
AU - Gümüş, Zeynep H.
AU - Offit, Kenneth
AU - Joseph, Vijai
AU - Klein, Robert J.
N1 - Publisher Copyright:
©2022 American Association for Cancer Research
PY - 2022/7
Y1 - 2022/7
N2 - Background: 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. Methods: 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. Results: 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 ¼ 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. Conclusions: 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. Impact: These results suggest that future association studies of prostate cancer survival should consider various intervals over the course of disease.
AB - Background: 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. Methods: 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. Results: 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 ¼ 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. Conclusions: 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. Impact: These results suggest that future association studies of prostate cancer survival should consider various intervals over the course of disease.
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U2 - 10.1158/1055-9965.EPI-22-0053
DO - 10.1158/1055-9965.EPI-22-0053
M3 - Article
C2 - 35511739
AN - SCOPUS:85133980632
SN - 1055-9965
VL - 31
SP - 1466
EP - 1472
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 7
ER -