Genetic variation in the upstream region of ERG and prostate cancer.
2009 (English)In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 20, no 7, 1173-1180 p.Article in journal (Refereed) Published
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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
2009. Vol. 20, no 7, 1173-1180 p.
Cancer and Oncology
IdentifiersURN: urn:nbn:se:umu:diva-25816DOI: 10.1007/s10552-009-9305-3PubMedID: 19205910OAI: oai:DiVA.org:umu-25816DiVA: diva2:233977