title: Ser217Leu polymorphism of the HPC2/ELAC2 gene associated with prostatic cancer risk in Japanese men.
abstract: The HPC2/ELAC2 gene may be associated with hereditary/familial prostate cancer (PCa). Two common missense variants (Ser217Leu and Ala541Thr) have been reported in the gene. We performed mutational, allelotyping and expression analyses and a molecular epidemiological study to clarify the relations between this gene and prostatic diseases, including PCa and benign prostatic hyperplasia (BPH) in Japanese men. We screened for mutations in 109 patients with PCa including 11 patients from 1 hereditary and 9 familial PCa. Loss of heterozygosity and expression were analyzed. An epidemiological study was done in sporadic PCa (n=98) and BPH (n=143) using 1 novel (Ser627Leu) and 2 previously described polymorphisms of the HPC2/ELAC2 gene. Somatic or germline mutations were not confirmed in any cases of PCa. Loss of heterozygosity at 2 microsatellites, D17S1289 and D17S520, was detected in 1 of 38 and 1 of 35 cases, respectively. Expression analysis revealed decreased or absent mRNA expression in 6 of 38 tumors. Epidemiologic analysis showed that a Leu allele at codon 217 was significantly more frequent in patients with PCa than in controls (10.2% vs. 3.5%, odds ratio = 3.11; 95% confidence interval, 1.22-7.90). At codon 541, all patients with PCa or BPH and all control subjects had the Ala/Ala genotype. At codon 627, the incidence of the Leu variant was slightly, but not significantly, higher in patients with BPH than in controls (7.0% vs. 2.8%, odds ratio = 2.59, 95% confidence interval, 0.94-7.13, not statistically significant). We concluded that germline/somatic mutations of HPC2/ELAC2 are uncommon in PCa. Similarly, allelic imbalances at the gene locus and changes in expression are rare. Although no difference in allele frequency at Ser217Leu between patients with PCa and controls has been reported in a Western population, this polymorphism is a potential indicator of PCa risk in Japanese men and it should be examined in other ethnic groups.
authors.affiliation: Department of Pathology, Jikei University School of Medicine, Tokyo, Japan. toritaka@jikei.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Takahiko
authors.initials: T
authors.lastname: Katoh
authors.forename: Masakuni
authors.initials: M
authors.lastname: Furusato
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tsukino
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakao
authors.forename: Akemi
authors.initials: A
authors.lastname: Sudo
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Koichiro
authors.initials: K
authors.lastname: Akakura
authors.forename: Isao
authors.initials: I
authors.lastname: Ikemoto
authors.forename: Kouji
authors.initials: K
authors.lastname: Asano
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ito
authors.forename: Shin
authors.initials: S
authors.lastname: Wakui
authors.forename: Tomoko
authors.initials: T
authors.lastname: Muto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hano
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D006867:Hydrolases / Q000235:genetics; D007564:Japan / Q000453:epidemiology; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011470:Prostatic Hyperplasia / Q000453:epidemiology / Q000235:genetics; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C421605:ELAC2 protein, human; D009363:Neoplasm Proteins; D004247:DNA; D006867:Hydrolases