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Polymorphisms in telomere-associated genes, breast cancer susceptibility and prognosis

Varadi, Verena; Brendle, Annika; Brandt, Andreas; Johansson, Robert; Enquist, Kerstin; Henriksson, Roger; Svenson, Ulrika; Tavelin, Bjorn; Roos, Goran and Hemminki, Kari, et al. (2009) In European Journal of Cancer 45(17). p.3008-3016
Abstract
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, TERF21p, ACD, POT1, TNKS and TNKS2) in 782 incident... (More)
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, TERF21p, 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, 9S% 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. (C) 2009 Elsevier Ltd. All rights reserved. (Less)
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keywords
Single nucleotide, polymorphism, Telomere, Breast cancer, Case-control study
in
European Journal of Cancer
volume
45
issue
17
pages
3008 - 3016
publisher
IFAC & Elsevier Ltd.
external identifiers
  • wos:000272371100013
  • scopus:70350589292
ISSN
1879-0852
DOI
10.1016/j.ejca.2009.08.012
language
English
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yes
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049afbc2-c855-486a-974b-89d6d69e3c3d (old id 1533558)
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2010-01-27 16:04:32
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@article{049afbc2-c855-486a-974b-89d6d69e3c3d,
  abstract     = {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, TERF21p, 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, 9S% 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. (C) 2009 Elsevier Ltd. All rights reserved.},
  author       = {Varadi, Verena and Brendle, Annika and Brandt, Andreas and Johansson, Robert and Enquist, Kerstin and Henriksson, Roger and Svenson, Ulrika and Tavelin, Bjorn and Roos, Goran and Hemminki, Kari and Lenner, Per and Försti, Asta},
  issn         = {1879-0852},
  keyword      = {Single nucleotide,polymorphism,Telomere,Breast cancer,Case-control study},
  language     = {eng},
  number       = {17},
  pages        = {3008--3016},
  publisher    = {IFAC & Elsevier Ltd.},
  series       = {European Journal of Cancer},
  title        = {Polymorphisms in telomere-associated genes, breast cancer susceptibility and prognosis},
  url          = {http://dx.doi.org/10.1016/j.ejca.2009.08.012},
  volume       = {45},
  year         = {2009},
}