Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: An analysis of 12,082 prostate cancer cases.
Prostate Cancer Prostatic Dis
; 21(2): 228-237, 2018 06.
Article
in En
| MEDLINE
| ID: mdl-29298992
ABSTRACT
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.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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostatic Neoplasms
/
DNA Modification Methylases
/
Interleukin-4
/
Germ-Line Mutation
/
Polymorphism, Single Nucleotide
/
Tumor Suppressor Proteins
/
DNA Repair Enzymes
/
Proto-Oncogene Proteins c-akt
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Limits:
Adult
/
Aged
/
Aged80
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Prostate Cancer Prostatic Dis
Journal subject:
ENDOCRINOLOGIA
/
NEOPLASIAS
/
UROLOGIA
Year:
2018
Type:
Article
Affiliation country:
Australia