Dataset Information

Genome-wide linkage scan for prostate cancer susceptibility from the University of Michigan Prostate Cancer Genetics Project: suggestive evidence for linkage at 16q23.

ABSTRACT: Prostate cancer linkage studies have been used to localize rare and presumably highly penetrant cancer susceptibility genes. Underlying genetic heterogeneity, as well as the high sporadic background of the disease, has resulted in many signals that are often not reproducible between research studies.We conducted a SNP-based genome wide linkage scan on 131 Caucasian prostate cancer families participating in the University of Michigan Prostate Cancer Genetics Project (PCGP).The strongest evidence for linkage was detected at 16q23 (LOD = 2.70 at rs1079635). Prostate cancer linkage to the same region of 16q23 has been observed by others and the region contains several strong candidate genes including the known prostate cancer tumor suppressor genes ATBF1 and WWOX. This linkage signal was not detected in our prior linkage study on 175 PCGP families, illustrating the genetic heterogeneity underlying prostate cancer susceptibility.Further linkage studies in combination with tumor analyses from linked families are in progress to identify the putative hereditary prostate cancer gene at 16q23.

SUBMITTER: Lange EM

PROVIDER: S-EPMC2712837 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Genome-wide linkage scan for prostate cancer susceptibility from the University of Michigan Prostate Cancer Genetics Project: suggestive evidence for linkage at 16q23.

Lange Ethan M EM Beebe-Dimmer Jennifer L JL Ray Anna M AM Zuhlke Kimberly A KA Ellis Jaclyn J Wang Yunfei Y Walters Sarah S Cooney Kathleen A KA

The Prostate 20090301 4

<h4>Background</h4>Prostate cancer linkage studies have been used to localize rare and presumably highly penetrant cancer susceptibility genes. Underlying genetic heterogeneity, as well as the high sporadic background of the disease, has resulted in many signals that are often not reproducible between research studies.<h4>Methods</h4>We conducted a SNP-based genome wide linkage scan on 131 Caucasian prostate cancer families participating in the University of Michigan Prostate Cancer Genetics Pro ...[more]

PMID: 19035517

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Project description: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 (alpha) 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.

Dataset Information

Genome-wide linkage scan for prostate cancer susceptibility from the University of Michigan Prostate Cancer Genetics Project: suggestive evidence for linkage at 16q23.

Publications

Genome-wide linkage scan for prostate cancer susceptibility from the University of Michigan Prostate Cancer Genetics Project: suggestive evidence for linkage at 16q23.

Similar Datasets

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