Prostate Cancer, Hereditary, X-Linked 1

For a general discussion of hereditary prostate cancer, see 176807.

Xu et al. (1998) presented evidence for the location of a prostate cancer susceptibility gene, which they symbolized HPCX, on Xq27-q28. Heterogeneity estimates suggested that the gene accounts for approximately 16% of hereditary prostate cancer cases. The finding was consistent with the results of a previous population-based study suggesting an X-linked mode of inheritance of prostate cancer. Linkage to Xq27-q28 was observed in a combined study population of 360 prostate cancer families collected at 4 independent sites in North America, Finland, and Sweden. A maximum 2-point lod score of 4.60 was observed with DXS1113 at theta = 0.26 in the combined data set. Parametric multipoint and nonparametric analyses provided results consistent with the 2-point analysis. The estimation of the proportion of X-linked families appeared to be the same in each family collection. A candidate prostate cancer susceptibility gene on the X chromosome is the androgen receptor gene (AR; 313700). AR, however, is located at Xq12, over 50 cM from the region implicated in the study of Xu et al. (1998).

Peters et al. (2001) reported on linkage analysis at the putative HPCX locus in an independent set of 186 prostate cancer families. In 81 families with no evidence of male-to-male transmission, they found a lod score of 1.062 at theta = 0.28 with DXS984. Although this analysis did not show statistically significant evidence for the linkage of prostate cancer susceptibility to Xq27-q28, the results were considered consistent with a small percentage of families being linked to this region.

Cancel-Tassin et al. (2001) examined evidence for linkage to the HPCX locus in 64 (37 previously reported and 27 newly identified) families from southern and western Europe with at least 3 affected individuals with prostate cancer and an average age at diagnosis of 66.4 years. Using both parametric and nonparametric linkage methods, no significant evidence of linkage was observed. A subset of 18 pedigrees without male-to-male transmission showed negative or low positive 2-point lod scores and negative multipoint lod scores across the entire region.

Farnham et al. (2005) performed linkage analysis on 143 Utah pedigrees for the HPCX prostate cancer susceptibility locus. In a dataset containing pedigrees having no more than 5 generations, a multipoint theta lod score of 2.74 (p = 0.0002) was observed, which was considered statistically significant after correction for multiple testing. Theta lod is a linkage statistic that is analogous to a 2-point lod score but utilizes full multipoint haplotype information. For both the full-structure pedigrees (up to 7 generations) and the smaller subpedigrees, the linkage evidence was much reduced.

By linkage disequilibrium and haplotype analysis of Finnish families with X-linked prostate cancer with no male-to-male transmission, Baffoe-Bonnie et al. (2005) refined the HPCX locus to a 150-kb region on Xq27-q28 between markers D3S2390 and bG82i1.0.