FitzGerald, LM and Zhao, S and Leonardson, A and Geybels, MS and Kolb, S and Lin, DW and Wright, JL and Eeles, R and Kote-Jarai, Z and Govindasami, K and Giles, GG and Southey, MC and Schleutker, J and Tammela, TL and Sipeky, C and Penney, KL and Stampfer, MJ and Gronberg, H and Wiklund, F and Stattin, P and Hugosson, J and Karyadi, DM and Ostrander, EA and Feng, Z and Stanford, JL, Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: an analysis of 12,082 prostate cancer cases, Prostate Cancer and Prostatic Diseases, 21, (2) pp. 228-237. ISSN 1365-7852 (2018) [Refereed Article]
Copyright 2017 The Authors. Licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) https://creativecommons.org/licenses/by-nc-sa/4.0/
Methods: 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.
Results: 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).
Conclusions: 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.
|Item Type:||Refereed Article|
|Keywords:||prostate cancer, mortality, association study, meta-analysis|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Oncology and carcinogenesis|
|Research Field:||Cancer genetics|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||FitzGerald, LM (Dr Liesel Fitzgerald)|
|Deposited By:||Menzies Institute for Medical Research|
|Downloads:||78 View Download Statistics|
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