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Genetic variation in the upstream region of ERG and prostate cancer
Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.;Umea Univ, Dept Radiat Sci, Umea, Sweden..
Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.;Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA..
Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden..ORCID iD: 0000-0003-2046-5641
Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC USA..
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2009 (English)In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 20, no 7, p. 1173-1180Article in journal (Refereed) Published
Abstract [en]

A considerable fraction of prostate cancers harbor a gene fusion between the androgen-regulated TMPRSS2 and ERG, one of the most frequently over-expressed proto-oncogenes in prostate cancer. Here, we investigated if inherited genetic variation upstream of ERG alters prostate cancer risk and survival. We genotyped 21 haplotype tagging SNPs (htSNPs) covering 123 kb of 5'UTR DNA including exon 3 of ERG in 2,760 incident prostate cancer cases and 1,647 controls from a population-based Swedish case-control study (CAPS). Individual SNPs and haplotypes were tested for association with prostate cancer risk and survival. One haplotype-'CTCGTATG' located 100 kb upstream of ERG-was associated with lethal prostate cancer (HR, 1.36; 95% CI, 1.2-1.9, p = 0.006). Carriers of the variant 'T' allele of rs2836626 were diagnosed with higher TNM-stage (p = 0.009) and had an increased risk of prostate cancer-specific death (HR = 1.3; 95% CI, 1.1-1.7, p = 0.009). However, this association did not remain statistically significant after adjusting for multiple testing. We found overall no association between ERG variation and prostate cancer risk. Genetic variation upstream of ERG may alter prostate cancer stage and ultimately prostate cancer-specific death but it is unlikely that it plays a role in prostate cancer development.

Place, publisher, year, edition, pages
SPRINGER , 2009. Vol. 20, no 7, p. 1173-1180
Keywords [en]
Prostate cancer, ERG, Haplotype, Polymorphism, Survival
National Category
Health Sciences
Identifiers
URN: urn:nbn:se:mdh:diva-40700DOI: 10.1007/s10552-009-9305-3ISI: 000268775300014PubMedID: 19205910OAI: oai:DiVA.org:mdh-40700DiVA, id: diva2:1246091
Available from: 2018-09-06 Created: 2018-09-06 Last updated: 2018-09-06Bibliographically approved

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