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Prostate Cancer Mortality Associated with Aggregate Polymorphisms in Androgen-Regulating Genes: The Atherosclerosis Risk in the Communities (ARIC) Study.

Authors :
Prizment AE
McSweeney S
Pankratz N
Joshu CE
Hwang JH
Platz EA
Ryan CJ
Source :
Cancers [Cancers (Basel)] 2021 Apr 19; Vol. 13 (8). Date of Electronic Publication: 2021 Apr 19.
Publication Year :
2021

Abstract

Genetic variations in androgen metabolism may influence prostate cancer (PC) prognosis. Clinical studies consistently linked PC prognosis with four single nucleotide polymorphisms (SNPs) in the critical androgen-regulating genes: 3-beta-hydroxysteroid dehydrogenase ( HSD3B1 ) rs1047303, 5-alpha-reductase 2 ( SRD5A2 ) rs523349, and solute carrier organic ion ( SLCO2B1 ) rs1789693 and rs12422149. We tested the association of four androgen-regulating SNPs, individually and combined, with PC-specific mortality in the ARIC population-based prospective cohort. Men diagnosed with PC (N = 622; 79% White, 21% Black) were followed for death (N = 350) including PC death (N = 74). Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95%CI adjusting for center, age, stage, and grade at diagnosis using separate hazards for races. A priori genetic risk score (GRS) was created as the unweighted sum of risk alleles in the four pre-selected SNPs. The gain-of-function rs1047303C allele was associated PC-specific mortality among men with metastatic PC at diagnosis (HR = 4.89 per risk allele, p = 0.01). Higher GRS was associated with PC-specific mortality (per risk allele: HR = 1.26, p = 0.03). We confirmed that the gain-of-function allele in HSD3B1 rs1047303 is associated with greater PC mortality in men with metastatic disease. Additionally, our findings suggest a cumulative effect of androgen-regulating genes on PC-specific mortality; however, further validation is required.

Details

Language :
English
ISSN :
2072-6694
Volume :
13
Issue :
8
Database :
MEDLINE
Journal :
Cancers
Publication Type :
Academic Journal
Accession number :
33921650
Full Text :
https://doi.org/10.3390/cancers13081958