Polymorphisms in the prostate cancer susceptibility gene HPC2/ELAC2 in multiplex families and healthy controls

Two polymorphisms in the newly cloned prostate cancer susceptibility gene, HPC2/ELAC2, are suspected to be associated with an increased risk of develo ping the disease, These missense variants result in a serine (S) to leucine (L) substitution at amino acid residue 217 and an alanine (A) to threonine (T) substitution at residue 541, We genotyped these polymorphisms in 257 m ultiplex prostate cancer sibships and in 355 race-matched healthy unrelated controls, A significant increase in the frequency of the T allele is seen In the prostate cancer subjects compared with controls. There is, however, little evidence for excess clustering of the T allele within the multiplex families known to be segregating this allele, and there is no evidence for linkage of prostate cancer to the HPC2/ELAC2 region of chromosome 17p11.2 i n these families. The T allele shows no association with either Gleason sco re or age-of-onset in segregating families.