Genetic Linkage Analysis of Prostate Cancer Families to Xq27–28

Objectives: A recent linkage analysis of 360 families at high risk for prostate cancer identified the q27–28 region on chromosome X as the potential location of a gene involved in prostate cancer susceptibility. Here we report on linkage analysis at this putative HPCX locus in an independent set of 186 prostate cancer families participating in the Prostate Cancer Genetic Research Study (PROGRESS). Methods: DNA samples from these families were genotyped at 8 polymorphic markers spanning 14.3 cM of the HPCX region. Results: Two-point parametric analysis of the total data set resulted in positive lod scores at only two markers, DXS984 and DXS1193, with scores of 0.628 at a recombination fraction (θ) of 0.36 and 0.012 at θ = 0.48, respectively. The stratification of pedigrees according to the assumed mode of transmission increased the evidence of linkage at DXS984 in 81 families with no evidence of male-to-male transmission (lod = 1.062 at θ = 0.28). Conclusions: Although this analysis did not show statistically significant evidence for the linkage of prostate cancer susceptibility to Xq27–28, the results are consistent with a small percentage of families being linked to this region. The analysis further highlights difficulties in replicating linkage results in an etiologically heterogeneous, complexly inherited disease.