Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease

FitzGerald, Liesel M.; Patterson, Briony; Thomson, Russell; Polanowski, Andrea M.; Quinn, Stephen; Brohede, Jesper; Thornton, Timothy A.; Challis, David; Mackey, David A.; Dwyer, Terence; Foote, Simon J.; Hannan, Garry N.; Stankovich, Jim; McKay, James; Dickinson, Joanne L.

doi:10.1038/ejhg.2008.171

Cited by 27 publications

(18 citation statements)

References 37 publications

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“…With the completion of the human genome project, high‐throughput genomic analysis platforms now permit identification of candidate cancer risk genes in large population studies 1‐3. This technology may be particularly helpful in diseases such as prostate cancer, where no dominant singular oncogenes have emerged.…”

Section: Introductionmentioning

confidence: 99%

“…With the completion of the human genome project, high-throughput genomic analysis platforms now permit identification of candidate cancer risk genes in large population studies. [1][2][3] This technology may be particularly helpful in diseases such as prostate cancer, where no dominant singular oncogenes have emerged. A recent genome-wide association study identified 5 genetic variants in chromosomal regions (8q24, 3 regions; 17q12; 17q24.3) that independently or cumulatively confer susceptibility to prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

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Successful recruitment of healthy African American men to genomic studies from high‐volume community health fairs

Patel¹,

Carr²,

Magjuka³

et al. 2011

Cancer

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BACKGROUND: Study of genomic data obtained from patient biospecimens is frequent in research of subjects with prostate and other epithelial malignancies. Understanding of the characteristics of healthy men who participate in genomic research is limited. METHODS: Patients were identified through the Prostate Cancer Genetic Risk Evaluation of SNPs Study and the Indiana University Cancer Biomarker Study, 2 population-based biomarker and cohort studies. Between 2006 and 2010, healthy Caucasian (n ¼ 774) and healthy African American (n ¼ 381) men were recruited and enrolled at high-volume free community health fairs. Each participant completed a demographic questionnaire and provided a blood sample for genomic research investigations. Frequency differences between demographic features of healthy African American and Caucasian men were compared and analyzed by 2-sample t test and multivariate logistic regression after adjusting potential confounding variables with significance at the P <.05 level. Features examined included: age, body mass index (BMI), income, education, marital status, tobacco, alcohol, family history, prostate-specific antigen (PSA) level, and prior prostate cancer screening history. RESULTS: Significant differences between healthy Caucasian and African American men participating in genomic research included: marital status (married, 69% Caucasian vs 46% African American, P< <.001), mean age (years, 58 Caucasian vs 54 African American, P <.001), mean BMI (kg/m 2 , 30.9 Caucasian vs 32.3 African American, P ¼.004), annual income (P ¼.038), education (P ¼.002), and mean PSA (ng/mL, 1.2 Caucasian vs 2.0 African American, P ¼.005). CONCLUSIONS: Significant demographic differences exist between healthy Caucasian and African American men choosing to participate in genomic research. These differences may be important in designing genomic research study recruitment strategies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Successful recruitment of healthy African American men to genomic studies from high‐volume community health fairs

Patel¹,

Carr²,

Magjuka³

et al. 2011

Cancer

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“…However, deletion of the α 2 integrin gene in cancer has not been reported. Genetic polymorphisms in the α 2 gene that potentially alter expression have been associated with prostate cancer susceptibility (46). Epigenetic modification of the α 2 gene promoter and regulation by microRNA are possibilities, since there is a progressive loss of expression in humans as tumor cells become less differentiated.…”

Section: Figurementioning

confidence: 99%

The α2β1 integrin is a metastasis suppressor in mouse models and human cancer

Ramirez¹,

Zhang²,

Madamanchi³

et al. 2011

J. Clin. Invest.

191

148

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Integrins regulate cell-cell and cell-matrix adhesion and thereby play critical roles in tumor progression and metastasis. Although work in preclinical models suggests that β 1 integrins may stimulate metastasis of a number of cancers, expression of the β 1 subunit alone has not been shown to be a useful prognostic indicator in human cancer patients. Here we have demonstrated that the α 2 β 1 integrin suppresses metastasis in a clinically relevant spontaneous mouse model of breast cancer. These data are consistent with previous studies indicating high expression of α 2 β 1 integrin in normal breast epithelium and loss of α 2 β 1 in poorly differentiated breast cancer. They are also consistent with our systematic analysis of microarray databases of human breast and prostate cancer, which revealed that decreased expression of the gene encoding α 2 integrin, but not genes encoding α 1 , α 3 , or β 1 integrin, was predictive of metastatic dissemination and decreased survival. The predictive value of α 2 expression persisted within both good-risk and poor-risk cohorts defined by estrogen receptor and lymph node status. Thus, the α 2 β 1 integrin functionally inhibits breast tumor metastasis, and α 2 expression may serve as an important biomarker of metastatic potential and patient survival.

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“…FitzGerald et al. [119] have selected a large prostate cancer pedigree for a genome‐wide linkage analysis from a population that is genetically homogeneous. They found a 14Mb haplotype at chromosome 5p13–q12.…”

Section: Chromosomal Locimentioning

confidence: 99%

Gene polymorphisms and prostate cancer: the evidence

et al. 2009

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OBJECTIVE Prostate cancer is still the most frequent noncutaneous male malignancy and is the second most common cause of cancer death. Genetic factors have been extensively studied in different countries. In addition, numerous genome–wide association studies have been performed in developed countries. Genetic tests will be applied in the near future for diagnosis, therapeutic, and prognostic significance. Therefore, we reviewed the association of several important pathways and genes with critical functions in prostate cancer development or progression. MATERIALS AND METHODS We performed a PubMed® search using several key words such as prostate cancer, names of important genes with critical function, and polymorphisms. Then, we reviewed retrieved articles as well as relevant articles from 1997 to 2009. RESULTS There are conflicting results of studies on some gene polymorphisms in association with prostate cancer. Most of the inconsistent results have been reported in studies investigating the vitamin D receptor gene polymorphism in association with prostate cancer. Genes related to angiogenesis and cell adhesion genes are more promising. Following results of future studies, the use of antibodies blocking over‐expressed genes or proteins may be supported in patients with prostate cancer. CONCLUSIONS The difference between the results of studies on gene polymorphisms in prostate cancer may be explained partly by ethnic differences, limited sample size, and other risk or protective factors modifying these effects. Genome‐wide studies are currently performed in developed countries and extensive use of this type of analysis may merit consideration in other countries. Furthermore, future studies are needed to further investigate environmental and diet factors interactions with genetic factors.

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Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease

Cited by 27 publications

References 37 publications

Successful recruitment of healthy African American men to genomic studies from high‐volume community health fairs

Successful recruitment of healthy African American men to genomic studies from high‐volume community health fairs

The α2β1 integrin is a metastasis suppressor in mouse models and human cancer

Gene polymorphisms and prostate cancer: the evidence

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