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.