Genetic linkage analysis of prostate cancer families to Xq27-28

Objectives: A recent linkage analysis of 360 families at high risk for pros tate cancer identified the q27-28 region on chromosome X as the potential l ocation of a gene involved in prostate cancer susceptibility. Here we repor t on linkage analysis at this putative HPCX locus in an independent set of 186 prostate cancer families participating in the Prostate Cancer Genetic R esearch Study (PROGRESS). Methods: DNA samples from these families were gen otyped at 8 polymorphic markers spanning 14.3 cM of the HPCX region. Result s: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 (theta) of 0.36 and 0.012 at theta = 0.48, respec tively. The stratification of pedigrees according to the assumed mode of tr ansmission increased the evidence of linkage at DXS984 in 81 families with no evidence of male-to-male transmission (lod = 1.062 at theta = 0.28). Con clusions: Although this analysis did not show statistically significant evi dence for the linkage of prostate cancer susceptibility to Xq27-28, the res ults are consistent with a small percentage of families being linked to thi s region. The analysis further highlights difficulties in replicating linka ge results in an etiologically heterogeneous, complexly inherited disease. Copyright (C) 2000 S. Karger AG, Basel.