TY - JOUR
T1 - Linkage and association studies of prostate cancer susceptibility
T2 - Evidence for linkage at 8p22-23
AU - Xu, J.
AU - Zheng, S. L.
AU - Hawkins, G. A.
AU - Faith, D. A.
AU - Kelly, B.
AU - Isaacs, S. D.
AU - Wiley, K. E.
AU - Chang, B. L.
AU - Ewing, C. M.
AU - Bujnovszky, P.
AU - Carpten, J. D.
AU - Bleecker, E. R.
AU - Walsh, P. C.
AU - Trent, J. M.
AU - Meyers, D. A.
AU - Isaacs, W. B.
N1 - Funding Information:
The authors thank all the study subjects who participated in this study. This work was partially supported by National Cancer Institute SPORE grant CA58236 and by two grants from the Department of Defense (to W.B.I. and J.X.).
PY - 2001
Y1 - 2001
N2 - Multiple lines of evidence have implicated the short arm of chromosome 8 as harboring genes important in prostate carcinogenesis. Although most of this evidence comes from the identification of frequent somatic alterations of 8p loci in prostate cancer cells (e.g., loss of heterozygosity), studies have also suggested a role for 8p genes in mediation of inherited susceptibility to prostate cancer. To further examine this latter possibility, we performed linkage analyses, in 159 pedigrees affected by hereditary prostate cancer (HPC), using 24 markers on the short arm of chromosome 8. In the complete set of families, evidence for prostate cancer linkage was found at 8p22-23, with a peak HLOD of 1.84 (P = .004), and an estimate of the proportion of families linked (α) of 0.14, at D8S1130. In the 79 families with average age at diagnosis >65 years, an allele-sharing LOD score of 2.64 (P = .0005) was observed, and six markers spanning a distance of 10 cM had LOD scores >2.0. Interestingly, the small number of Ashkenazi Jewish pedigrees (n = 11) analyzed in this study contributed disproportionately to this linkage. Mutation screening in HPC probands and association analyses in case subjects (a group that includes HPC probands and unrelated case subjects) and unaffected control subjects were carried out for the putative prostate cancer - susceptibility gene, PG1, previously localized to the 8p22-23 region. No statistical differences in the allele, genotype, or haplotype frequencies of the SNPs or other sequence variants in the PG1 gene were observed between case and control subjects. However, case subjects demonstrated a trend toward higher homozygous rates of less-frequent alleles in all three PG1 SNPs, and overtransmission of a PG1 variant to case subjects was observed. In summary, these results provide evidence for the existence of a prostate cancer - susceptibility gene at 8p22-23. Evaluation of the PG1 gene and other candidate genes in this area appears warranted.
AB - Multiple lines of evidence have implicated the short arm of chromosome 8 as harboring genes important in prostate carcinogenesis. Although most of this evidence comes from the identification of frequent somatic alterations of 8p loci in prostate cancer cells (e.g., loss of heterozygosity), studies have also suggested a role for 8p genes in mediation of inherited susceptibility to prostate cancer. To further examine this latter possibility, we performed linkage analyses, in 159 pedigrees affected by hereditary prostate cancer (HPC), using 24 markers on the short arm of chromosome 8. In the complete set of families, evidence for prostate cancer linkage was found at 8p22-23, with a peak HLOD of 1.84 (P = .004), and an estimate of the proportion of families linked (α) of 0.14, at D8S1130. In the 79 families with average age at diagnosis >65 years, an allele-sharing LOD score of 2.64 (P = .0005) was observed, and six markers spanning a distance of 10 cM had LOD scores >2.0. Interestingly, the small number of Ashkenazi Jewish pedigrees (n = 11) analyzed in this study contributed disproportionately to this linkage. Mutation screening in HPC probands and association analyses in case subjects (a group that includes HPC probands and unrelated case subjects) and unaffected control subjects were carried out for the putative prostate cancer - susceptibility gene, PG1, previously localized to the 8p22-23 region. No statistical differences in the allele, genotype, or haplotype frequencies of the SNPs or other sequence variants in the PG1 gene were observed between case and control subjects. However, case subjects demonstrated a trend toward higher homozygous rates of less-frequent alleles in all three PG1 SNPs, and overtransmission of a PG1 variant to case subjects was observed. In summary, these results provide evidence for the existence of a prostate cancer - susceptibility gene at 8p22-23. Evaluation of the PG1 gene and other candidate genes in this area appears warranted.
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U2 - 10.1086/321967
DO - 10.1086/321967
M3 - Article
C2 - 11443539
AN - SCOPUS:0034918268
SN - 0002-9297
VL - 69
SP - 341
EP - 350
JO - American journal of human genetics
JF - American journal of human genetics
IS - 2
ER -