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Polymorphisms in the mitochondrial oxidative phosphorylation chain genes as prognostic markers for colorectal cancer

Lascorz, Jesus; Bevier, Melanie; Schoenfels, Witigo V.; Kalthoff, Holger; Aselmann, Heiko; Beckmann, Jan; Egberts, Jan; Buch, Stephan; Becker, Thomas and Schreiber, Stefan, et al. (2012) In BMC Medical Genetics 13.
Abstract
Background: Currently, the TNM classification of malignant tumours based on clinicopathological staging remains the standard for colorectal cancer (CRC) prognostication. Recently, we identified the mitochondrial oxidative phosphorylation chain as a consistently overrepresented category in the published gene expression profiling (GEP) studies on CRC prognosis. Methods: We evaluated associations of putative regulatory single nucleotide polymorphisms (SNPs) in genes from the oxidative phosphorylation chain with survival and disease prognosis in 613 CRC patients from Northern Germany (PopGen cohort). Results: Two SNPs in the 3' untranslated region of UQCRB (complex III), rs7836698 and rs10504961, were associated with overall survival (HR =... (More)
Background: Currently, the TNM classification of malignant tumours based on clinicopathological staging remains the standard for colorectal cancer (CRC) prognostication. Recently, we identified the mitochondrial oxidative phosphorylation chain as a consistently overrepresented category in the published gene expression profiling (GEP) studies on CRC prognosis. Methods: We evaluated associations of putative regulatory single nucleotide polymorphisms (SNPs) in genes from the oxidative phosphorylation chain with survival and disease prognosis in 613 CRC patients from Northern Germany (PopGen cohort). Results: Two SNPs in the 3' untranslated region of UQCRB (complex III), rs7836698 and rs10504961, were associated with overall survival (HR = 0.52, 95% CI 0.32-0.85 and HR = 0.64, 95% CI 0.42-0.99, for TT carriers). These associations were restricted to the group of patients with cancer located in the colon (HR = 0.42, 95% CI 0.22-0.82 and HR = 0.46, 95% CI 0.25-0.83). Multivariate analysis indicated that both markers might act as independent prognostic markers. Additionally, the TT carriers were similar to 2 times more likely to develop tumours in the colon than in the rectum. Two SNPs in COX6B1 (complex IV) were associated with lymph node metastasis in a dominant model (rs6510502, OR = 1.75, 95% CI 1.20-2.57; rs10420252, OR = 1.68, 95% CI 1.11-2.53); rs6510502 was associated also with distant metastasis (OR = 1.67, 95% CI 1.09-2.56 in a dominant model). Conclusions: This is the first report suggesting that markers in genes from the mitochondrial oxidative chain might be prognostic factors for CRC. Additional studies replicating the presented findings are needed. (Less)
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BMC Medical Genetics
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13
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BioMed Central
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  • wos:000307961100001
  • scopus:84862232907
ISSN
1471-2350
DOI
10.1186/1471-2350-13-31
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English
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ddb91c5c-a8e4-432c-8254-6795a081de01 (old id 3157861)
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2012-11-01 09:36:38
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2017-09-10 04:01:45
@article{ddb91c5c-a8e4-432c-8254-6795a081de01,
  abstract     = {Background: Currently, the TNM classification of malignant tumours based on clinicopathological staging remains the standard for colorectal cancer (CRC) prognostication. Recently, we identified the mitochondrial oxidative phosphorylation chain as a consistently overrepresented category in the published gene expression profiling (GEP) studies on CRC prognosis. Methods: We evaluated associations of putative regulatory single nucleotide polymorphisms (SNPs) in genes from the oxidative phosphorylation chain with survival and disease prognosis in 613 CRC patients from Northern Germany (PopGen cohort). Results: Two SNPs in the 3' untranslated region of UQCRB (complex III), rs7836698 and rs10504961, were associated with overall survival (HR = 0.52, 95% CI 0.32-0.85 and HR = 0.64, 95% CI 0.42-0.99, for TT carriers). These associations were restricted to the group of patients with cancer located in the colon (HR = 0.42, 95% CI 0.22-0.82 and HR = 0.46, 95% CI 0.25-0.83). Multivariate analysis indicated that both markers might act as independent prognostic markers. Additionally, the TT carriers were similar to 2 times more likely to develop tumours in the colon than in the rectum. Two SNPs in COX6B1 (complex IV) were associated with lymph node metastasis in a dominant model (rs6510502, OR = 1.75, 95% CI 1.20-2.57; rs10420252, OR = 1.68, 95% CI 1.11-2.53); rs6510502 was associated also with distant metastasis (OR = 1.67, 95% CI 1.09-2.56 in a dominant model). Conclusions: This is the first report suggesting that markers in genes from the mitochondrial oxidative chain might be prognostic factors for CRC. Additional studies replicating the presented findings are needed.},
  author       = {Lascorz, Jesus and Bevier, Melanie and Schoenfels, Witigo V. and Kalthoff, Holger and Aselmann, Heiko and Beckmann, Jan and Egberts, Jan and Buch, Stephan and Becker, Thomas and Schreiber, Stefan and Hampe, Jochen and Hemminki, Kari and Försti, Asta and Schafmayer, Clemens},
  issn         = {1471-2350},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {BMC Medical Genetics},
  title        = {Polymorphisms in the mitochondrial oxidative phosphorylation chain genes as prognostic markers for colorectal cancer},
  url          = {http://dx.doi.org/10.1186/1471-2350-13-31},
  volume       = {13},
  year         = {2012},
}