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 1298 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% CI=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.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2022 May 05 [Epub ahead of print]
Xiaoyu Song, Meng Ru, Zoe Steinsnyder, Kaitlyn Tkachuk, Ryan P Kopp, John Sullivan, Zeynep H Gümüş, Kenneth Offit, Vijai Joseph, Robert J Klein
Icahn School of Medicine at Mount Sinai, New York, New York, United States., Icahn School of Medicine at Mount Sinai, New York, NY, United States., Memorial Sloan Kettering Cancer Center, New York, NY, United States., Oregon Health & Science University, Portland, OR, United States.