title: Association of susceptibility alleles in ELAC2/HPC2, RNASEL/HPC1, and MSR1 with prostate cancer severity in European American and African American men.
abstract: Reported associations of ELAC2/HPC2, RNASEL/HPC1, and MSR1 with prostate cancer have been inconsistent and understudied in African Americans. We evaluated the role of 16 sequence variants in these genes with prostate cancer using 888 European American and 131 African American cases, and 473 European American and 163 African American, controls. We observed significant differences in ELAC2, RNASEL, and MSR1 allele frequencies by race. However, we did not observe significant associations between prostate cancer and any variants examined for both races combined. Associations were observed when stratified by race, family history, or disease severity. European American men homozygous for MSR1 IVS7delTTA had an elevated risk for localized stage [odds ratio, (OR), 3.5; 95% confidence interval (95% CI), 1.4-6.9], low-grade (OR, 3.2; 95% CI, 1.4-7.3) disease overall, and with low-grade (OR, 2.9; 95% CI, 1.2-7.2) or late-stage disease (OR, 5.2; 95% CI, 1.1-25.7) in family history-negative African Americans. MSR1 Arg293X was associated with family history-negative high-grade disease (OR, 4.0; 95% CI, 1.1-14.1) in European Americans. RNASEL Arg462Gln was associated with low-grade (OR, 1.5; 95% CI, 1.04-2.2) and early-stage (OR, 1.5; 95% CI, 1.02-2.1) disease in family history-negative European Americans. In family history-positive individuals, Arg462Gln was inversely associated with low-grade (OR, 0.43; 95% CI, 0.21-0.88) and low-stage (OR, 0.46; 95% CI, 0.22-0.95) disease. In African Americans, Arg462Gln was associated with positive family history high-stage disease (OR, 14.8; 95% CI, 1.6-135.7). Meta-analyses revealed significant associations of prostate cancer with MSR1 IVS7delTTA, -14,742 A>G, and Arg293X in European Americans; Asp174Tyr in African Americans; RNASEL Arg462Gln in European American's overall and in family history-negative disease; and Glu265X in family history-positive European Americans. Therefore, MSR1 and RNASEL may play a role in prostate cancer progression and severity.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Health System, 7 Gates West, 3400 Spruce Street, Philadelphia, PA 19104, USA. hanna.rennert@uphs.upenn.edu
authors.forename: Hanna
authors.initials: H
authors.lastname: Rennert
authors.forename: Charnita M
authors.initials: CM
authors.lastname: Zeigler-Johnson
authors.forename: Kathakali
authors.initials: K
authors.lastname: Addya
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Finley
authors.forename: Amy H
authors.initials: AH
authors.lastname: Walker
authors.forename: Elaine
authors.initials: E
authors.lastname: Spangler
authors.forename: Debra G B
authors.initials: DG
authors.lastname: Leonard
authors.forename: Alan
authors.initials: A
authors.lastname: Wein
authors.forename: S Bruce
authors.initials: SB
authors.lastname: Malkowicz
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D004722:Endoribonucleases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D015143:Philadelphia / Q000453:epidemiology; D011471:Prostatic Neoplasms / Q000145:classification / Q000208:ethnology / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D012720:Severity of Illness Index; D044465:White People / Q000235:genetics
chemical_list: C421605:ELAC2 protein, human; C495139:MSR1 protein, human; D009363:Neoplasm Proteins; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease