ELAC2/HPC2 involvement in hereditary and sporadic prostate cancer

The ELAC2/HPC2 gene at 17p11 is the first candidate gene identified for hum an prostate cancer (PRCA) based on linkage analysis and positional cloning (S. V. Tavtigian et at. Nat. Genet., 27:172-180, 2001). A truncating mutati on was found in one hereditary prostate cancer (HPC) family, whereas two mi ssense variants, Ser217Leu and Ala541Thr, were reported to be associated wi th increased PRCA risk in the general population. Here, we screened for mut ations of the ELAC2/HPC2 gene in 66 Finnish HPC families. Several sequence variants, including a new exonic variant (Glu622Val) were found, but none o f the mutations were truncating. We then analyzed the frequency of the thre e found missense variants in 1365 individuals, including hereditary (n = 10 7) and un;elected (n = 467) PRCA, benign prostatic hyperplasia (n = 223), a nd population controls (568 healthy male blood donors). Ser217Leu and Ala54 1Thr variants carried no significantly elevated risk for HPC or PRCA, altho ugh the latter variant was associated with benign prostatic hyperplasia. Th e previously undescribed Glu622Val variant had a 1.0% population prevalence , but a significantly higher frequency in PRCA cases (3.0% odds ratio, 2.94 ; 95% confidence interval, 1.05-8.23). We conclude that ELAC2/HPC2 truncati ng mutations are rare in HPC, but that rare variants of the ELAC2/HPC2 requ ire additional study as risk factors for PRCA in the general population.