| Autor: |
FitzGerald, L. M., Zhao, S., Leonardson, A., Geybels, M. S., Kolb, S., Lin, D. W., Wright, J. L., Eeles, R., Kote-Jarai, Z., Govindasami, K., Giles, G. G., Southey, M. C., Schleutker, J., Tammela, T. L., Sipeky, C., Penney, K. L., Stampfer, M. J., Gronberg, H., Wiklund, F., Stattin, P., Hugosson, J., Karyadi, D. M., Ostrander, E. A., Feng, Z., Stanford, J. L. |
| Zdroj: |
Prostate Cancer and Prostatic Diseases; June 2018, Vol. 21 Issue: 2 p228-237, 10p |
| Abstrakt: |
Prostate cancer (PCa) is a leading cause of mortality and genetic factors can influence tumour aggressiveness. Several germline variants have been associated with PCa-specific mortality (PCSM), but further replication evidence is needed. Twenty-two previously identified PCSM-associated genetic variants were genotyped in seven PCa cohorts (12,082 patients; 1544 PCa deaths). For each cohort, Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for risk of PCSM associated with each variant. Data were then combined using a meta-analysis approach. Fifteen SNPs were associated with PCSM in at least one of the seven cohorts. In the meta-analysis, after adjustment for clinicopathological factors, variants in the MGMT(rs2308327; HR 0.90; p-value = 3.5 × 10−2) and IL4(rs2070874; HR 1.22; p-value = 1.1 × 10−3) genes were confirmed to be associated with risk of PCSM. In analyses limited to men diagnosed with local or regional stage disease, a variant in AKT1, rs2494750, was also confirmed to be associated with PCSM risk (HR 0.81; p-value = 3.6 × 10−2). This meta-analysis confirms the association of three genetic variants with risk of PCSM, providing further evidence that genetic background plays a role in PCa-specific survival. While these variants alone are not sufficient as prognostic biomarkers, these results may provide insights into the biological pathways modulating tumour aggressiveness. |
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