A1 Refereed original research article in a scientific journal
Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: An analysis of 12,082 prostate cancer cases
Authors: L. M. FitzGerald, S. Zhao, A. Leonardson, M. S. Geybels, S. Kolb, D. W. Lin, J. L. Wright, R. Eeles, Z. Kote-Jarai, K. Govindasami, G. G. Giles, M. C. Southey, J. Schleutker, T. L. Tammela, C. Sipeky, K. L. Penney, M. J. Stampfer, H. Gronberg, F. Wiklund, P. Stattin, J. Hugosson, D. M. Karyadi, E. A. Ostrander, Z. Feng, J. L. Stanford
Publisher: Nature Publishing Group
Publication year: 2018
Journal: Prostate Cancer and Prostatic Diseases
Journal name in source: Prostate Cancer and Prostatic Diseases
Volume: 21
Issue: 2
First page : 228
Last page: 237
Number of pages: 10
eISBN: 1476-5608
ISSN: 1365-7852
DOI: https://doi.org/10.1038/s41391-017-0029-2
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/30148009
Background
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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