Dataset Information

Linkage and association studies of prostate cancer susceptibility: evidence for linkage at 8p22-23.

ABSTRACT: 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.

SUBMITTER: Xu J

PROVIDER: S-EPMC1235306 | biostudies-other | 2001 Aug

REPOSITORIES: biostudies-other

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Linkage and association studies of prostate cancer susceptibility: evidence for linkage at 8p22-23.

Xu J J Zheng S L SL Hawkins G A GA Faith D A DA Kelly B B Isaacs S D SD Wiley K E KE Chang B B Ewing C M CM Bujnovszky P P Carpten J D JD Bleecker E R ER Walsh P C PC Trent J M JM Meyers D A DA Isaacs W B WB

American journal of human genetics 20010706 2

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 ...[more]

PMID: 11443539

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Project description:Exposure to environmental carcinogens can cause damages to DNA. If not properly repaired, the DNA damages may increase the risk of carcinogenesis. Xeroderma pigmentosum group G (XPG) gene is an essential gene in the nucleotide excision repair (NER) pathway. The association between XPG polymorphisms and cancer susceptibility has been the focus of attention in the molecular epidemiology of cancer. However, the conclusions have been divergent. Therefore, we conducted a comprehensive meta-analysis to precisely evaluate the association of 3 frequently investigated XPG polymorphisms (rs751402, rs873601, and rs2296147) with cancer risk.Pubmed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) were searched for relevant studies in English and Chinese. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the association between XPG polymorphisms (rs751402, rs873601, and rs2296147) and cancer risk.Twenty-three studies were included. Overall, there was no significant association between rs751402 polymorphism and overall cancer risk under the 5 gene models. However, we observed strong correlation between rs751402 polymorphism and gastric cancer (C vs T: OR=1.21, 95% CI?=?1.00-1.26, P?=?.045; TC vs CC: OR?=?1.12, 95% CI?=?1.00-1.24, P?=?.041; TC/TT vs CC: OR?=?1.13, 95% CI?=?1.02-1.26, P?=?.020). There was a significant correlation between rs873601 polymorphism and cancer risk under the homozygous model (GG vs AA: OR?=?1.16, 95% CI?=?1.07-1.26, P?=?.001). Moreover, significant association with breast cancer was detected for rs873601 polymorphism under the allele contrast model (G vs A: OR?=?1.10, 95% CI?=?1.02-1.20, P?=?.021). In the subgroup of Asian, rs873601 polymorphism was related to the susceptibility to cancer (G vs A: OR?=?1.07, 95% CI?=?1.03-1.12, P?=?.010; GG vs AA: OR?=?1.15, 95% CI?=?1.06-1.26, P?=?.001; AG/AA vs GG: OR?=?1.08, 95% CI?=?1.01-1.15, P?=?.031; AA vs AG/GG: OR?=?1.13, 95% CI?=?1.05-1.21, P?=?.001). Significant association between rs2296147 polymorphism and cancer risk were observed in Asian population (CT vs TT: OR?=?0.93, 95% CI?=?0.87-0.99, P?=?.036).Our meta-analysis suggested that the rs873601 polymorphism was significantly associated with overall cancer risk. The moderate effects of rs751402 and rs2296147 polymorphism on cancer susceptibility might be highly dependent on cancer type and ethnicity, respectively. Large studies are needed to validate our findings, especially in Caucasian and African population.

Dataset Information

Linkage and association studies of prostate cancer susceptibility: evidence for linkage at 8p22-23.

Publications

Linkage and association studies of prostate cancer susceptibility: evidence for linkage at 8p22-23.

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