Journal Article

Association between common mtDNA variants and all-cause or colorectal cancer mortality

Evropi Theodoratou, Farhat V.N. Din, Susan M. Farrington, Roseanne Cetnarskyj, Rebecca A. Barnetson, Mary E. Porteous, Malcolm G. Dunlop, Harry Campbell and Albert Tenesa

in Carcinogenesis

Volume 31, issue 2, pages 296-301
Published in print February 2010 | ISSN: 0143-3334
Published online November 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp237
Association between common mtDNA variants and all-cause or colorectal cancer mortality

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Mutations in the mitochondrial DNA (mtDNA) have been found to be present in several types of tumours including tumours of the large bowel. However, their role in cancer development and prognosis is still to be resolved. We used 2838 cases from a large Scottish colorectal cancer (CRC) case–control study to examine whether inherited genetic variation at the mtDNA influenced all-cause and CRC-specific mortality. We examined 140 tagging mtDNA variants including nine haplotypes commonly found in European populations. After applying three Cox proportional hazard models adjusted for American Joint Committee on Cancer (AJCC) stage, age and sex, three single nucleotide polymorphisms, two located in the 12S ribosomal RNA region (G752A and G1440A) and one in the nicotinamide adenine dinucleotide dehydrogenase subunit 2 region (ND2) region (G4770A), were statistically significantly associated with all-cause (Model I P-values: 0.0001, 0.002 and 0.002, respectively) and CRC-specific mortality (Model I P-values: 5 × 10−5, 0.0003 and 0.0006, respectively). The H and U haplogroups were associated with an increased and decreased CRC risk, respectively, but with P-values of borderline significance and only after AJCC stage adjustment. In conclusion, the findings of the current study suggest a link between three common mtDNA variants and CRC prognosis. These findings are interesting and consistent with other biological knowledge but need to be confirmed through replication in independent cohorts.

Journal Article.  4587 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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