Luchini Claudio, Nottegar Alessia, Vaona Alberto, Stubbs Brendon, Demurtas Jacopo, Maggi Stefania, Veronese Nicola
Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Piazzale Scuro, 10, 37134 Verona, Italy.
Department of Surgery, Section of Anatomical Pathology, San Bortolo Hospital, Vicenza, Italy.
Cancer Genet. 2018 Aug;224-225:29-36. doi: 10.1016/j.cancergen.2018.04.003. Epub 2018 Apr 11.
Recent studies highlighted the role of mitochondrial dysregulation in cancer, suggesting that the different mitochondrial haplogroups might play a role in tumorigenesis and risk of cancer development. Our aim is to investigate whether any mitochondrial haplogroups carried a significant higher risk of cancer development in a large prospective cohort of North American people. The haplogroup assignment was performed by a combination of sequencing and PCR-RFLP techniques. Our specific outcome of interest was the incidence of any cancer during follow-up period. Overall, 3222 participants were included in the analysis. Women having I, J, K haplogroup reported a significant higher incidence of cancer compared to people with other haplogroups (p < 0.0001), whilst in men non association was found. In the multivariate analysis, women having I, J, K mitochondrial haplogroup reported a 50% increased risk of cancer (HR = 1.50; 95%CI: 1.04-2.16; p = 0.03). This gender-linked association may be partly explained by the role of mitochondrial function in female-specific (e.g. BRCA-driven) oncogenesis, but further studies are needed to better understand this potential correlation. Our findings may have important implications for cancer epidemiology and prevention.
最近的研究强调了线粒体功能失调在癌症中的作用，这表明不同的线粒体单倍群可能在肿瘤发生和癌症发展风险中发挥作用。我们的目的是在一个大型北美人群前瞻性队列中研究是否有任何线粒体单倍群具有显著更高的癌症发展风险。单倍群的确定是通过测序和PCR-RFLP技术相结合来进行的。我们感兴趣的具体结果是随访期间任何癌症的发病率。总体而言，3222名参与者被纳入分析。与其他单倍群的人相比，拥有I、J、K单倍群的女性报告的癌症发病率显著更高（p<0.0001），而在男性中未发现关联。在多变量分析中，拥有I、J、K线粒体单倍群的女性报告患癌风险增加了50%（HR=1.50；95%CI：1.04-2.16；p=0.03）。这种与性别相关的关联可能部分由线粒体功能在女性特异性（如BRCA驱动）肿瘤发生中的作用来解释，但需要进一步研究以更好地理解这种潜在的相关性。我们的发现可能对癌症流行病学和预防具有重要意义。
