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Open Access Research article

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

Jesus Lascorz1, Melanie Bevier1, Witigo V Schönfels2, Holger Kalthoff3, Heiko Aselmann2, Jan Beckmann2, Jan Egberts2, Stephan Buch45, Thomas Becker2, Stefan Schreiber5, Jochen Hampe5, Kari Hemminki16, Asta Försti16* and Clemens Schafmayer24

Author affiliations

1 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, Heidelberg, 69120, Germany

2 Department of General and Thoracic Surgery, Christian-Albrechts-University, Kiel, Germany

3 Division of Molecular Oncology, Institute for Experimental Cancer Research, Christian-Albrechts-University, Kiel, Germany

4 POPGEN Biobank Project, Christian-Albrechts-University, Kiel, Germany

5 Department of General Internal Medicine, Christian-Albrechts-University, Kiel, Germany

6 Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden

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Citation and License

BMC Medical Genetics 2012, 13:31  doi:10.1186/1471-2350-13-31

Published: 30 April 2012

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 ~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.