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Polymorphisms in telomere-associated genes, breast cancer susceptibility and prognosis
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
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2009 (Engelska)Ingår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 45, nr 17, s. 3008-3016Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Telomeres are essential structures for maintaining chromosomal stability and their length has been reported to correlate with cancer risk and clinical outcome. Single nucleotide polymorphisms (SNPs) in genes encoding telomere-associated proteins could affect telomere length and chromosomal stability by influencing gene expression or protein configuration in the telomeres. Here, we report the results of the first association study on genetic variation in telomere-associated genes and their effect on telomere length, breast cancer (BC) susceptibility and prognosis. We genotyped 14 potentially functional and most informative SNPs in nine telomere-associated genes (TERT, TEP1, TERF1, TERF2, TERF2IP, ACD, POT1, TNKS and TNKS2) in 782 incident BC cases and 1559 matched controls. Relative telomere length (RTL) varied statistically significantly between the genotypes of the SNPs rs446977 (TEP1, p=0.04), rs938886 (TEP1, p=0.04) and rs6990097 (TNKS, p=0.04). However, none of them was associated with BC susceptibility and only rs6990097 correlated with regional lymph node metastasis (odds ratio (OR) 1.38, 95% confidence interval (CI) 1.08-1.77). The strongest association with BC susceptibility was observed for rs3785074 (TERF2, OR 0.51, 95% CI 0.31-0.83) and rs10509637 (TNKS2, OR 1.33, 95% CI 1.08-1.62). Haplotype and diplotype analysis confirmed the association of the TNKS2 gene with BC susceptibility. rs3785074 (TERF2) was additionally associated with histologic grade (OR 1.44, 95% CI 1.08-1.92) and negative oestrogen receptor status (OR 2.93, 95% CI 1.13-7.58). None of the SNPs showed a significant correlation with survival of the breast cancer patients. With these results, none of the SNPs represents any valuable prognostic marker for BC.

Ort, förlag, år, upplaga, sidor
Oxford: Pergamon , 2009. Vol. 45, nr 17, s. 3008-3016
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URN: urn:nbn:se:umu:diva-30048DOI: 10.1016/j.ejca.2009.08.012PubMedID: 19766477OAI: oai:DiVA.org:umu-30048DiVA, id: diva2:279103
Tillgänglig från: 2009-12-01 Skapad: 2009-12-01 Senast uppdaterad: 2018-06-08Bibliografiskt granskad

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Johansson, RobertEnquist, KerstinHenriksson, RogerSvenson, UlrikaTavelin, BjörnRoos, GöranLenner, Per

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Johansson, RobertEnquist, KerstinHenriksson, RogerSvenson, UlrikaTavelin, BjörnRoos, GöranLenner, Per
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OnkologiNäringsforskningPatologi
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