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

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Lascorz, Jesus (author)

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

Article/chapterEnglish2012

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2012-04-30
Springer Science and Business Media LLC,2012
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LIBRIS-ID:oai:lup.lub.lu.se:ddb91c5c-a8e4-432c-8254-6795a081de01
https://lup.lub.lu.se/record/3157861URI
https://doi.org/10.1186/1471-2350-13-31DOI

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Language:English
Summary in:English

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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.

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Bevier, Melanie (author)
Schoenfels, Witigo V. (author)
Kalthoff, Holger (author)
Aselmann, Heiko (author)
Beckmann, Jan (author)
Egberts, Jan (author)
Buch, Stephan (author)
Becker, Thomas (author)
Schreiber, Stefan (author)
Hampe, Jochen (author)
Hemminki, KariLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups(Swepub:lu)med-khk (author)
Försti, AstaLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups(Swepub:lu)med-asf (author)
Schafmayer, Clemens (author)
Allmänmedicin och klinisk epidemiologiForskargrupper vid Lunds universitet (creator_code:org_t)

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In:BMC Medical Genetics: Springer Science and Business Media LLC131471-2350

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By the author/editor: Lascorz, Jesus; Bevier, Melanie; Schoenfels, Witi ...; Kalthoff, Holger; Aselmann, Heiko; Beckmann, Jan; show more...; Egberts, Jan; Buch, Stephan; Becker, Thomas; Schreiber, Stefa ...; Hampe, Jochen; Hemminki, Kari; Försti, Asta; Schafmayer, Clem ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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By the university: Lund University

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