title: Association between common mtDNA variants and all-cause or colorectal cancer mortality.
abstract: 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 x 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.
authors: Public Health Sciences, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK. e.theodoratou@ed.ac.uk
authors: Evropi
authors: E
authors: Theodoratou
authors: Farhat V N
authors: FV
authors: Din
authors: Susan M
authors: SM
authors: Farrington
authors: Roseanne
authors: R
authors: Cetnarskyj
authors: Rebecca A
authors: RA
authors: Barnetson
authors: Mary E
authors: ME
authors: Porteous
authors: Malcolm G
authors: MG
authors: Dunlop
authors: Harry
authors: H
authors: Campbell
authors: Albert
authors: A
authors: Tenesa
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D004272:DNA, Mitochondrial