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Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP
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2007 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 99, no 24, p. 1836-1844Article in journal (Refereed) Published
Abstract [en]

Background: The consistent finding of a genetic susceptibility to prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. These variants could be useful in screening and treatment. Methods: We performed an exploratory genome-wide association scan in 498 men with aggressive prostate cancer and 494 control subjects selected from a population-based case-control study in Sweden. We combined the results of this scan with those for aggressive prostate cancer from the publicly available Cancer Genetic Markers of Susceptibility (CGEMS) Study. Single-nucleotide polymorphisms (SNPs) that showed statistically significant associations with the risk of aggressive prostate cancer based on two-sided allele tests were tested for their association with aggressive prostate cancer in two independent study populations composed of individuals of European or African American descent using one-sided tests and the genetic model (dominant or additive) associated with the lowest value in the exploratory study. Results: Among the approximately 60000 SNPs that were common to our study and CGEMS, we identified seven that had a similar (positive or negative) and statistically significant (P<.01) association with the risk of aggressive prostate cancer in both studies. Analysis of the distribution of these SNPs among 1032 prostate cancer patients and 571 control subjects of European descent indicated that one, rs1571801, located in the DAB2IP gene, which encodes a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer (one-sided P value =. 004). The association was also statistically significant in an African American study population that included 210 prostate cancer patients and 346 control subjects (one-sided P value =. 02). Conclusion: A genetic variant in DAB2IP may be associated with the risk of aggressive prostate cancer and should be evaluated further.

Place, publisher, year, edition, pages
2007. Vol. 99, no 24, p. 1836-1844
Keywords [en]
guanosine triphosphatase activating protein, DAB2IP protein, human, tumor marker, unclassified drug, adult, African American, aged, allele, article, cancer risk, case control study, controlled study, dab2ip gene, gene, gene location, genetic association, genetic code, genetic marker, genetic model, genetic susceptibility, genetic variability, human, major clinical study, male, population research, priority journal, prostate cancer, single nucleotide polymorphism, statistical significance, suppressor gene, Sweden, Caucasian, genetic predisposition, genetics, genotype, middle aged, prostate tumor, risk, risk assessment, risk factor, tumor suppressor gene, African Americans, Case-Control Studies, European Continental Ancestry Group, Genes, Tumor Suppressor, Genetic Predisposition to Disease, Humans, Odds Ratio, Polymorphism, Single Nucleotide, Prostatic Neoplasms, ras GTPase-Activating Proteins, Risk Factors, Tumor Markers, Biological
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Health Sciences
Identifiers
URN: urn:nbn:se:mdh:diva-40791DOI: 10.1093/jnci/djm250Scopus ID: 2-s2.0-38449103390OAI: oai:DiVA.org:mdh-40791DiVA, id: diva2:1246161
Available from: 2018-09-06 Created: 2018-09-06 Last updated: 2018-09-06Bibliographically approved

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Bälter, Katarina

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