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ELAC2/HPC2 Involvement in Hereditary and Sporadic Prostate Cancer¹

Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, FIN-33101 Tampere, Finland [A. R., T. I., N. M., M. P. M., P. A. K., J. S.]; Tampere School of Public Health, University of Tampere, FIN-33014 Tampere, Finland [V. A.]; Department of Urology, Tampere University Hospital and Medical School, University of Tampere, FIN-33521 Tampere, Finland [M. P. M., T. L. J. T.]; Department of Clinical Genetics, Tampere University Hospital, FIN-33521 Tampere, Finland [P. A. K.]; Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892 [O-P. K.]

The ELAC2/HPC2 gene at 17p11 is the first candidate gene identified for human prostate cancer (PRCA) based on linkage analysis and positional cloning (S. V.Tavtigian et al. Nat. Genet., 27:172–180, 2001). A truncating mutation was found in one hereditary prostate cancer (HPC) family, whereas two missense variants, Ser217Leu and Ala541Thr, were reported to be associated with increased PRCA risk in the general population. Here, we screened for mutations of the ELAC2/HPC2 gene in 66 Finnish HPC families. Several sequence variants, including a new exonic variant (Glu622Val) were found, but none of the mutations were truncating. We then analyzed the frequency of the three found missense variants in 1365 individuals, including hereditary (n = 107) and unselected (n = 467) PRCA, benign prostatic hyperplasia (n = 223), and population controls (568 healthy male blood donors). Ser217Leu and Ala541Thr variants carried no significantly elevated risk for HPC or PRCA, although the latter variant was associated with benign prostatic hyperplasia. The 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 truncating mutations are rare in HPC, but that rare variants of the ELAC2/HPC2 require additional study as risk factors for PRCA in the general population.

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