title: Association of HPC2/ELAC2 polymorphisms with risk of prostate cancer in a population-based study.
abstract: Genetic polymorphism in HPC2/ELAC2 was recently associated with risk of sporadic prostate cancer. To determine the contribution of two HPC2/ELAC2 missense variants (Ser217Leu and Ala541Thr) to the risk of developing prostate cancer, we conducted a population-based case-control study of middle-aged men (40-64 years). Cases (n=591) were ascertained from the Seattle-Puget Sound Surveillance, Epidemiology, and End Results Cancer Registry and Controls (n=538) from the same general population were identified through random-digit dialing. Subjects were residents of King County, Washington, and were frequency matched on age. Cases (32%) had a slightly higher frequency of the Leu217 variant compared with controls (29%), but there were no differences in the frequency of the Thr541 allele (4%). When considering joint genotypes, white men homozygous for the Leu217 variant on an Ala541/Ala541 background had an increased risk of prostate cancer [odds ratio (OR)=1.84; 95% confidence interval (CI), 1.11-3.06]. Different risk profiles were also observed when cases were stratified by disease aggressiveness. Men with at least one Leu217 allele had an elevated risk (OR=1.34; 95% CI, 1.02-1.76) of less aggressive prostate cancer (localized stage and Gleason score < or = 7), with a stronger association among men with two Leu217 alleles (OR=1.73; 95% CI, 1.08-2.77). The Ala541Thr polymorphism was not associated with risk, and neither variant was associated with more aggressive prostate cancer phenotypes. We estimate that the Ser217Leu genotype may account for approximately 14% of less aggressive prostate cancer cases and 9% of all sporadic cases in the general United States population of white men <age 65 years.
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005787:Gene Frequency; D014644:Genetic Variation; D006720:Homozygote; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D044465:White People
chemical_list: C421605:ELAC2 protein, human; D009363:Neoplasm Proteins; D007930:Leucine