Linkage Analysis of Chromosome 1q Markers in 136 Prostate Cancer Families

Eeles, Rosalind; Durocher, Francine; Edwards, Steve; Teare, M. Dawn; Badzioch, Mike D.; Hamoudi, Rifat; Gill, Sandra; Biggs, Patrick J.; Dearnaley, David P.; Ardern‐Jones, Audrey; Dowe, Anna; Shearer, Robert; McLennan, Dawn L.; Norman, Reid L.; Ghadirian, Parviz; Aprikian, Armen; Ford, Deborah; Amos, Chris; King, Terri M.; Labrie, Fernand; Simard, Jacques; Narod, Steven A.; Easton, Douglas F.; Foulkes, William D.

doi:10.1086/301745

Cited by 107 publications

(35 citation statements)

References 16 publications

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“…7 Two other studies of 136 and 49 high-risk families have not con®rmed linkage at 1q24-25, although neither study included African ± Americans and the larger study contained fewer affected individuals per family on average than the other studies. 8,9 Together these studies suggest that HPC1 accounts for at least some cases of hereditary prostate cancer, especially in those families with four or more affected relatives. Estimation of the overall proportion of hereditary disease referable to HPC1 and the relative contribution of this locus in various ethnic groups must await further study.…”

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confidence: 82%

Does a family history of prostate cancer result in more aggressive disease?

Klein

Kupelian

Witte

1998

Prostate Cancer Prostatic Dis

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Current epidemiologic and genetic data suggest the hypothetical paradigm that prostate cancer occurs in three forms: sporadic, familial, and hereditary ( Figure 1). Sporadic cases are not associated with familial inheritance patterns, while familial cancer is de®ned as simple clustering of two or more cases within a family. The existence of hereditary prostate cancer, a subset of the familial form, is suggested by three epidemiologic observations enumerated by Carter et al 1 : (1) relatives of patients younger than 55 y are at higher risk of getting prostate cancer than those with older affected relatives; (2) there is stronger familial clustering in families with early onset of prostate cancer; and (3) the number of affected family members and their age at onset are the most important determinants of risk among relatives. 1 It has been estimated that the hereditary form of this disease accounts for 43% of early onset cancers (age 55 y or younger) but only 9% of all prostate cancer occurring by age 85 y. 2 Eeles et al 3 have summarized the published literature concerning familial clustering of prostate cancer. In casecontrol studies the relative risk of prostate cancer in ®rst-degree relatives of affected men ranges from 1.76 ± 11. In studies comparing the percentage of cases vs controls with a positive family history of prostate cancer, the relative risk ranges from 0.64 ± 7.5. Cohort studies in the United States 4 and Sweden 5 estimate relative risks of prostate cancer of 2.2 and 1.70, respectively, in men with affected relatives. Using segregation analysis in nuclear families Carter et al 1 estimated hazard ratios ranging from 1.4 ± 7

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confidence: 82%

Does a family history of prostate cancer result in more aggressive disease?

Klein

Kupelian

Witte

1998

Prostate Cancer Prostatic Dis

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“…[1][2][3] Although these associations are statistically significant, it remains unclear to what extent these high-risk genotypes are associated with aggressive forms of prostate cancer. 4,5 A primary goal of evaluating biomarkers for the early detection of prostate cancer is to distinguish patients who will eventually develop metastases from those with more indolent forms of cancer.…”

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confidence: 99%

New variants at 10q26 and 15q21 are associated with aggressive prostate cancer in a genome-wide association study from a prostate biopsy screening cohort

Nam

Zhang

Siminovitch

et al. 2011

Cancer Biology & Therapy

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; Toronto ON Canada Purpose: To identify and examine polymorphisms of genes associated with aggressive and clinical significant forms of prostate cancer among a screening cohort.Experimental Design: We conducted a genome-wide association study among patients with aggressive forms of prostate cancer and biopsy-proven normal controls ascertained from a prostate cancer screening program. We then examined significant associations of specific polymorphisms among a prostate cancer screened cohort to examine their predictive ability in detecting prostate cancer.Results: We found significant associations between aggressive prostate cancer and five single nucleotide polymorphisms (SNPs) in the 10q26 (rs10788165, rs10749408, and rs10788165, p value for association 1.3 ¾ 10 210 to 3.2 ¾ 10 211 ) and 15q21 (rs4775302 and rs1994198, p values for association 3.1 ¾ 10 28 to 8.2 ¾ 10 29 ) regions. Results of a replication study done in 3439 patients undergoing a prostate biopsy, revealed certain combinations of these SNPs to be significantly associated not only with prostate cancer but with aggressive forms of prostate cancer using an established classification criterion for prostate cancer progression (odds ratios for intermediate to high-risk disease 1.8-3.0, p value 0.003-0.001). These SNP combinations were also important clinical predictors for prostate cancer detection based on nomogram analysis that assesses prostate cancer risk.Conclusions: Five SNPs were found to be associated with aggressive forms of prostate cancer. We demonstrated potential clinical applications of these associations.

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“…A maximum multipoint logarithm of odds (LOD) score of 5.43 under the assumption of heterogeneity was observed, with 34% of families predicted to be linked. Several replication studies were published subsequently, with some confirming the initial findings (7)(8)(9), whereas others could not (10)(11)(12)(13)(14). A large metaanalysis of 772 families provided weak evidence overall, suggesting that about 6% of families could attribute their disease to HPC1 (15).…”

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confidence: 96%

Identification of a prostate cancer susceptibility locus on chromosome 7q11–21 in Jewish families

Friedrichsen

Stanford

Isaacs

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Results from over a dozen prostate cancer susceptibility genomewide scans, encompassing some 1,500 hereditary prostate cancer families, indicate that prostate cancer is an extremely heterogeneous disease with multiple loci contributing to overall susceptibility. In an attempt to reduce locus heterogeneity, we performed a genomewide linkage scan for prostate cancer susceptibility genes with 36 Jewish families, which represent a stratification of hereditary prostate cancer families with potentially increased locus homogeneity. The 36 Jewish families represent a combined dataset of 17 Jewish families from the Fred Hutchinson Cancer Research Center-based Prostate Cancer Genetic Research Study dataset and 19 Ashkenazi Jewish families collected at Johns Hopkins University. All available family members, including 94 affected men, were genotyped at markers distributed across the genome with an average interval of <10 centimorgans. Nonparametric multipoint linkage analyses were the primary approach, although parametric analyses were performed as well. Our strongest signal was a significant linkage peak at 7q11-21, with a nonparametric linkage (NPL) score of 3.01 (P ‫؍‬ 0.0013). Simulations indicated that this corresponds to a genomewide empirical P ‫؍‬ 0.006. All other regions had NPL P values >0.02. After genotyping additional markers within the 7q11-21 peak, the NPL score increased to 3.35 (P ‫؍‬ 0.0004) at D7S634 with an allele-sharing logarithm of odds of 3.12 (P ‫؍‬ 0.00007). These studies highlight the utility of analyzing defined sets of families with a common origin for reducing locus heterogeneity problems associated with studying complex traits.

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Linkage Analysis of Chromosome 1q Markers in 136 Prostate Cancer Families

Cited by 107 publications

References 16 publications

Does a family history of prostate cancer result in more aggressive disease?

Does a family history of prostate cancer result in more aggressive disease?

New variants at 10q26 and 15q21 are associated with aggressive prostate cancer in a genome-wide association study from a prostate biopsy screening cohort

Identification of a prostate cancer susceptibility locus on chromosome 7q11–21 in Jewish families

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