Association of chromosomal locus 8q24 and risk of prostate cancer: A hospital-based study of German patients treated with brachytherapy

Abstract Background Genetic susceptibility contributes to the risk of prostate cancer but the underlying genes are largely unknown. Polymorphic loci on chromosome 8q24 have emerged as possible risk factors for breast and prostate cancer from genome-wide association studies. Objective We aimed to def...

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Veröffentlicht in:Urologic oncology 2009-07, Vol.27 (4), p.373-376
Hauptverfasser: Meyer, Andreas, M.D, Schürmann, Peter, Ghahremani, Maryam, Kocak, Ertan, Brinkhaus, Maria-Jantje, Bremer, Michael, M.D, Karstens, Johann H., M.D, Hagemann, Jörn, M.D, Machtens, Stefan, M.D, Dörk, Thilo, Ph.D
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container_end_page 376
container_issue 4
container_start_page 373
container_title Urologic oncology
container_volume 27
creator Meyer, Andreas, M.D
Schürmann, Peter
Ghahremani, Maryam
Kocak, Ertan
Brinkhaus, Maria-Jantje
Bremer, Michael, M.D
Karstens, Johann H., M.D
Hagemann, Jörn, M.D
Machtens, Stefan, M.D
Dörk, Thilo, Ph.D
description Abstract Background Genetic susceptibility contributes to the risk of prostate cancer but the underlying genes are largely unknown. Polymorphic loci on chromosome 8q24 have emerged as possible risk factors for breast and prostate cancer from genome-wide association studies. Objective We aimed to define the risks associated with two single nucleotide polymorphisms, rs1447295 and rs13281615, in a hospital-based series of prostate cancer patients treated with brachytherapy. Material and methods We analyzed genomic DNA samples of 488 prostate cancer cases undergoing brachytherapy at Hannover Medical School, and of 462 male controls from the same location. Genotyping was performed using 5′-exonuclease allelic discrimination assays, and results were evaluated with χ2 tests and logistic regression analyses. Results We investigated whether rs1447295 and rs13281615 are associated with disease risk in a hospital-based prostate cancer case-control series from Northern Germany. The rare allele of rs1447295 was observed at higher frequency among cases than among hospital-based controls (13.9% vs. 10.2%, P = 0.01), and there was a dose-dependent trend towards a higher prevalence of heterozygous and homozygous carriers among the prostate cancer patients (per allele OR 1.42, 95% CI 1.07; 1.87, P = 0.02). By contrast, the rare allele of rs13281615 did not predispose to prostate cancer (per allele OR 0.84, 95% CI 0.70; 1.00, P = 0.05). The distribution of combined 8q24 genotypes was significantly different between cases and controls ( P = 0.01). Conclusion Our results corroborate previous reports of 8q24 as a prostate cancer susceptibility locus and provide evidence for rs1447295 as a potentially important genetic marker. Further studies are required to confirm whether the adjacent breast cancer-associated variant rs13281615 may be inversely associated with prostate cancer risk.
doi_str_mv 10.1016/j.urolonc.2008.04.010
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Polymorphic loci on chromosome 8q24 have emerged as possible risk factors for breast and prostate cancer from genome-wide association studies. Objective We aimed to define the risks associated with two single nucleotide polymorphisms, rs1447295 and rs13281615, in a hospital-based series of prostate cancer patients treated with brachytherapy. Material and methods We analyzed genomic DNA samples of 488 prostate cancer cases undergoing brachytherapy at Hannover Medical School, and of 462 male controls from the same location. Genotyping was performed using 5′-exonuclease allelic discrimination assays, and results were evaluated with χ2 tests and logistic regression analyses. Results We investigated whether rs1447295 and rs13281615 are associated with disease risk in a hospital-based prostate cancer case-control series from Northern Germany. The rare allele of rs1447295 was observed at higher frequency among cases than among hospital-based controls (13.9% vs. 10.2%, P = 0.01), and there was a dose-dependent trend towards a higher prevalence of heterozygous and homozygous carriers among the prostate cancer patients (per allele OR 1.42, 95% CI 1.07; 1.87, P = 0.02). By contrast, the rare allele of rs13281615 did not predispose to prostate cancer (per allele OR 0.84, 95% CI 0.70; 1.00, P = 0.05). The distribution of combined 8q24 genotypes was significantly different between cases and controls ( P = 0.01). Conclusion Our results corroborate previous reports of 8q24 as a prostate cancer susceptibility locus and provide evidence for rs1447295 as a potentially important genetic marker. Further studies are required to confirm whether the adjacent breast cancer-associated variant rs13281615 may be inversely associated with prostate cancer risk.</description><identifier>ISSN: 1078-1439</identifier><identifier>EISSN: 1873-2496</identifier><identifier>DOI: 10.1016/j.urolonc.2008.04.010</identifier><identifier>PMID: 18625567</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adenocarcinoma - diagnosis ; Adenocarcinoma - genetics ; Adenocarcinoma - therapy ; Adult ; Aged ; Association study ; Biological and medical sciences ; Brachytherapy ; Brachytherapy - methods ; Chromosomes, Human, Pair 8 ; Genetic predisposition ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Germany ; Humans ; Male ; Medical sciences ; Middle Aged ; Nephrology. Urinary tract diseases ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Prostate cancer susceptibility ; Prostatic Neoplasms - diagnosis ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - therapy ; Risk ; Tumors ; Tumors of the urinary system ; Urinary tract. Prostate gland ; Urology</subject><ispartof>Urologic oncology, 2009-07, Vol.27 (4), p.373-376</ispartof><rights>Elsevier Inc.</rights><rights>2009 Elsevier Inc.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-e06a3bf145ff6aed31596c628d86ed3c2d907c1410c87dd80ead83da4d46eded3</citedby><cites>FETCH-LOGICAL-c448t-e06a3bf145ff6aed31596c628d86ed3c2d907c1410c87dd80ead83da4d46eded3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.urolonc.2008.04.010$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3538,27906,27907,45977</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=21723509$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18625567$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Meyer, Andreas, M.D</creatorcontrib><creatorcontrib>Schürmann, Peter</creatorcontrib><creatorcontrib>Ghahremani, Maryam</creatorcontrib><creatorcontrib>Kocak, Ertan</creatorcontrib><creatorcontrib>Brinkhaus, Maria-Jantje</creatorcontrib><creatorcontrib>Bremer, Michael, M.D</creatorcontrib><creatorcontrib>Karstens, Johann H., M.D</creatorcontrib><creatorcontrib>Hagemann, Jörn, M.D</creatorcontrib><creatorcontrib>Machtens, Stefan, M.D</creatorcontrib><creatorcontrib>Dörk, Thilo, Ph.D</creatorcontrib><title>Association of chromosomal locus 8q24 and risk of prostate cancer: A hospital-based study of German patients treated with brachytherapy</title><title>Urologic oncology</title><addtitle>Urol Oncol</addtitle><description>Abstract Background Genetic susceptibility contributes to the risk of prostate cancer but the underlying genes are largely unknown. Polymorphic loci on chromosome 8q24 have emerged as possible risk factors for breast and prostate cancer from genome-wide association studies. Objective We aimed to define the risks associated with two single nucleotide polymorphisms, rs1447295 and rs13281615, in a hospital-based series of prostate cancer patients treated with brachytherapy. Material and methods We analyzed genomic DNA samples of 488 prostate cancer cases undergoing brachytherapy at Hannover Medical School, and of 462 male controls from the same location. Genotyping was performed using 5′-exonuclease allelic discrimination assays, and results were evaluated with χ2 tests and logistic regression analyses. Results We investigated whether rs1447295 and rs13281615 are associated with disease risk in a hospital-based prostate cancer case-control series from Northern Germany. The rare allele of rs1447295 was observed at higher frequency among cases than among hospital-based controls (13.9% vs. 10.2%, P = 0.01), and there was a dose-dependent trend towards a higher prevalence of heterozygous and homozygous carriers among the prostate cancer patients (per allele OR 1.42, 95% CI 1.07; 1.87, P = 0.02). By contrast, the rare allele of rs13281615 did not predispose to prostate cancer (per allele OR 0.84, 95% CI 0.70; 1.00, P = 0.05). The distribution of combined 8q24 genotypes was significantly different between cases and controls ( P = 0.01). Conclusion Our results corroborate previous reports of 8q24 as a prostate cancer susceptibility locus and provide evidence for rs1447295 as a potentially important genetic marker. Further studies are required to confirm whether the adjacent breast cancer-associated variant rs13281615 may be inversely associated with prostate cancer risk.</description><subject>Adenocarcinoma - diagnosis</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - therapy</subject><subject>Adult</subject><subject>Aged</subject><subject>Association study</subject><subject>Biological and medical sciences</subject><subject>Brachytherapy</subject><subject>Brachytherapy - methods</subject><subject>Chromosomes, Human, Pair 8</subject><subject>Genetic predisposition</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-Wide Association Study</subject><subject>Germany</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Polymorphism, Genetic</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Prostate cancer susceptibility</subject><subject>Prostatic Neoplasms - diagnosis</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - therapy</subject><subject>Risk</subject><subject>Tumors</subject><subject>Tumors of the urinary system</subject><subject>Urinary tract. Prostate gland</subject><subject>Urology</subject><issn>1078-1439</issn><issn>1873-2496</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFksGO1SAUhhujccbRR9Cw0V0rtJRSF05uJjqaTOJCXRMunKbcaUuHQzV9Al9bmtto4sYVEL7zH87_k2UvGS0YZeLtqViCH_xkipJSWVBeUEYfZZdMNlVe8lY8TnvayJzxqr3IniGeKGVcMvY0u2BSlHUtmsvs1wHRG6ej8xPxHTF98KNHP-qBDN4sSORDyYmeLAkO7zdkDh6jjkCMngyEd-RAeo-zi3rIjxrBEoyLXTf0FsKoJzIneZgikhggFVry08WeHIM2_Rp7CHpen2dPOj0gvNjXq-z7xw_fbj7ld19uP98c7nLDuYw5UKGrY8d43XVCg61Y3QojSmmlSCdT2pY2hnFGjWyslRS0lZXV3PJ0n4ir7M1ZN03xsABGNTo0MAx6Ar-gEg3nbdXWCazPoEnjYoBOzcGNOqyKUbUloE5qT0BtCSjKVUog1b3aGyzHEezfqt3yBLzeAY1GD11ILjr8w5WsKauatom7PnOQ7PjhICg0yUUD1gUwUVnv_vuU9_8omMFNLjW9hxXw5JcwJa8VU1gqqr5u32X7LVTSpMKb6jeR_b79</recordid><startdate>20090701</startdate><enddate>20090701</enddate><creator>Meyer, Andreas, M.D</creator><creator>Schürmann, Peter</creator><creator>Ghahremani, Maryam</creator><creator>Kocak, Ertan</creator><creator>Brinkhaus, Maria-Jantje</creator><creator>Bremer, Michael, M.D</creator><creator>Karstens, Johann H., M.D</creator><creator>Hagemann, Jörn, M.D</creator><creator>Machtens, Stefan, M.D</creator><creator>Dörk, Thilo, Ph.D</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20090701</creationdate><title>Association of chromosomal locus 8q24 and risk of prostate cancer: A hospital-based study of German patients treated with brachytherapy</title><author>Meyer, Andreas, M.D ; Schürmann, Peter ; Ghahremani, Maryam ; Kocak, Ertan ; Brinkhaus, Maria-Jantje ; Bremer, Michael, M.D ; Karstens, Johann H., M.D ; Hagemann, Jörn, M.D ; Machtens, Stefan, M.D ; Dörk, Thilo, Ph.D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c448t-e06a3bf145ff6aed31596c628d86ed3c2d907c1410c87dd80ead83da4d46eded3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adenocarcinoma - diagnosis</topic><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - therapy</topic><topic>Adult</topic><topic>Aged</topic><topic>Association study</topic><topic>Biological and medical sciences</topic><topic>Brachytherapy</topic><topic>Brachytherapy - methods</topic><topic>Chromosomes, Human, Pair 8</topic><topic>Genetic predisposition</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-Wide Association Study</topic><topic>Germany</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Polymorphism, Genetic</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Prostate cancer susceptibility</topic><topic>Prostatic Neoplasms - diagnosis</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - therapy</topic><topic>Risk</topic><topic>Tumors</topic><topic>Tumors of the urinary system</topic><topic>Urinary tract. Prostate gland</topic><topic>Urology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Meyer, Andreas, M.D</creatorcontrib><creatorcontrib>Schürmann, Peter</creatorcontrib><creatorcontrib>Ghahremani, Maryam</creatorcontrib><creatorcontrib>Kocak, Ertan</creatorcontrib><creatorcontrib>Brinkhaus, Maria-Jantje</creatorcontrib><creatorcontrib>Bremer, Michael, M.D</creatorcontrib><creatorcontrib>Karstens, Johann H., M.D</creatorcontrib><creatorcontrib>Hagemann, Jörn, M.D</creatorcontrib><creatorcontrib>Machtens, Stefan, M.D</creatorcontrib><creatorcontrib>Dörk, Thilo, Ph.D</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Urologic oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Meyer, Andreas, M.D</au><au>Schürmann, Peter</au><au>Ghahremani, Maryam</au><au>Kocak, Ertan</au><au>Brinkhaus, Maria-Jantje</au><au>Bremer, Michael, M.D</au><au>Karstens, Johann H., M.D</au><au>Hagemann, Jörn, M.D</au><au>Machtens, Stefan, M.D</au><au>Dörk, Thilo, Ph.D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of chromosomal locus 8q24 and risk of prostate cancer: A hospital-based study of German patients treated with brachytherapy</atitle><jtitle>Urologic oncology</jtitle><addtitle>Urol Oncol</addtitle><date>2009-07-01</date><risdate>2009</risdate><volume>27</volume><issue>4</issue><spage>373</spage><epage>376</epage><pages>373-376</pages><issn>1078-1439</issn><eissn>1873-2496</eissn><abstract>Abstract Background Genetic susceptibility contributes to the risk of prostate cancer but the underlying genes are largely unknown. Polymorphic loci on chromosome 8q24 have emerged as possible risk factors for breast and prostate cancer from genome-wide association studies. Objective We aimed to define the risks associated with two single nucleotide polymorphisms, rs1447295 and rs13281615, in a hospital-based series of prostate cancer patients treated with brachytherapy. Material and methods We analyzed genomic DNA samples of 488 prostate cancer cases undergoing brachytherapy at Hannover Medical School, and of 462 male controls from the same location. Genotyping was performed using 5′-exonuclease allelic discrimination assays, and results were evaluated with χ2 tests and logistic regression analyses. Results We investigated whether rs1447295 and rs13281615 are associated with disease risk in a hospital-based prostate cancer case-control series from Northern Germany. The rare allele of rs1447295 was observed at higher frequency among cases than among hospital-based controls (13.9% vs. 10.2%, P = 0.01), and there was a dose-dependent trend towards a higher prevalence of heterozygous and homozygous carriers among the prostate cancer patients (per allele OR 1.42, 95% CI 1.07; 1.87, P = 0.02). By contrast, the rare allele of rs13281615 did not predispose to prostate cancer (per allele OR 0.84, 95% CI 0.70; 1.00, P = 0.05). The distribution of combined 8q24 genotypes was significantly different between cases and controls ( P = 0.01). Conclusion Our results corroborate previous reports of 8q24 as a prostate cancer susceptibility locus and provide evidence for rs1447295 as a potentially important genetic marker. Further studies are required to confirm whether the adjacent breast cancer-associated variant rs13281615 may be inversely associated with prostate cancer risk.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>18625567</pmid><doi>10.1016/j.urolonc.2008.04.010</doi><tpages>4</tpages></addata></record>
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subjects Adenocarcinoma - diagnosis
Adenocarcinoma - genetics
Adenocarcinoma - therapy
Adult
Aged
Association study
Biological and medical sciences
Brachytherapy
Brachytherapy - methods
Chromosomes, Human, Pair 8
Genetic predisposition
Genetic Predisposition to Disease
Genome-Wide Association Study
Germany
Humans
Male
Medical sciences
Middle Aged
Nephrology. Urinary tract diseases
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Prostate cancer susceptibility
Prostatic Neoplasms - diagnosis
Prostatic Neoplasms - genetics
Prostatic Neoplasms - therapy
Risk
Tumors
Tumors of the urinary system
Urinary tract. Prostate gland
Urology
title Association of chromosomal locus 8q24 and risk of prostate cancer: A hospital-based study of German patients treated with brachytherapy
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