Mitochondrial dysfunction and risk of cancer.
BACKGROUND
Mitochondrial mutations are commonly reported in tumours, but it is unclear whether impaired mitochondrial function per se is a cause or consequence of cancer. To elucidate this, we examined the risk of cancer in a nationwide cohort of patients with mitochondrial dysfunction.


METHODS
We used nationwide results on genetic testing for mitochondrial disease and the Danish Civil Registration System, to construct a cohort of 311 patients with mitochondrial dysfunction. A total of 177 cohort members were identified from genetic testing and 134 genetically untested cohort members were matrilineal relatives to a cohort member with a genetically confirmed maternally inherited mDNA mutation. Information on cancer was obtained by linkage to the Danish Cancer Register. Standardised incidence ratios (SIRs) were used to assess the relative risk of cancer.


RESULTS
During 7334 person-years of follow-up, 19 subjects developed a primary cancer. The corresponding SIR for any primary cancer was 1.06 (95% confidence interval 0.68-1.63). Subgroup analyses according to mutational subtype yielded similar results, for example, a SIR of 0.94 (95% CI 0.53 to 1.67) for the m.3243A>G maternally inherited mDNA mutation, cases=13.


CONCLUSIONS
Patients with mitochondrial dysfunction do not appear to be at increased risk of cancer compared with the general population.
Department of Epidemiology Research, National Health Surveillance and Research, Statens Serum Institut, 2300 Copenhagen S, Denmark.
M
M
Lund
1] Department of Epidemiology Research, National Health Surveillance and Research, Statens Serum Institut, 2300 Copenhagen S, Denmark [2] Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA [3] Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen N, Denmark.
M
M
Melbye
Department of Epidemiology Research, National Health Surveillance and Research, Statens Serum Institut, 2300 Copenhagen S, Denmark.
L J
LJ
Diaz
Department of Clinical Genetics, Molecular Genetic Laboratory, Rigshospitalet, University of Copenhagen, 2100 Copenhagen Ø, Denmark.
M
M
Duno
Department of Epidemiology Research, National Health Surveillance and Research, Statens Serum Institut, 2300 Copenhagen S, Denmark.
J
J
Wohlfahrt
Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen Ø, Denmark.
J
J
Vissing
D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology*; D009154:Mutation; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D012306:Risk; D012307:Risk Factors; D055815:Young Adult
D004272:DNA, Mitochondrial