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Mitochondrial dysfunction and risk of cancer

机译:线粒体功能障碍和患癌症的风险

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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.
机译:背景:线粒体突变通常在肿瘤中报道,但不清楚线粒体功能受损本身是癌症的原因还是后果。为了阐明这一点,我们检查了全国线粒体功能障碍患者队列中的癌症风险。方法:我们利用全国范围的线粒体疾病基因检测结果和丹麦民事登记系统,建立了311名线粒体功能障碍患者队列。通过基因测试共鉴定出177名同龄人,其中134名未经基因测试的同龄人是母系的亲戚,而该同龄人具有经遗传学确认的母体遗传性mDNA突变。有关癌症的信息是通过与丹麦癌症登记处联系获得的。使用标准化的发病率(SIR)评估癌症的相对风险。结果:在7334人年的随访期间,有19名受试者患了原发性癌症。任何原发癌的相应SIR为1.06(95%置信区间0.68–1.63)。根据突变亚型进行的亚组分析得出了相似的结果,例如,m.3243A> G母系遗传的mDNA突变的SIR为0.94(95%CI为0.53至1.67),案例= 13。结论:与普通人群相比,线粒体功能障碍的患者似乎没有增加患癌症的风险。

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