Skonieczna Katarzyna, Jawień Arkadiusz, Marszałek Andrzej, Grzybowski Tomasz
Division of Molecular and Forensic Genetics, Department of Forensic Medicine, Faculty of Medicine, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
Department of Vascular Surgery and Angiology, Faculty of Medicine, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
Arch Med Sci. 2019 Jan 16;16(2):366-373. doi: 10.5114/aoms.2018.80893. eCollection 2020.
To date, several nuclear DNA variants have been shown to be associated with increased risk of developing colorectal cancer. Despite the fact that mitochondria play an important role in carcinogenesis, little is known about inherited mitochondrial DNA mutations that could be involved in this disease. Thus, potential associations between inherited mutations in the entire mitochondrial genomes and colorectal cancer were analysed in this study.
Two hundred mitogenome sequences determined for colorectal cancer patients and healthy individuals from Poland were used to investigate the association between mtDNA alleles or haplogroups and colorectal cancer. Additional mtDNA control region haplotypes determined for 1353 individuals from the general Polish population were used for comparison of haplogroup and certain allele frequencies between case and control groups.
The non-R clades together with their diagnostic T alleles at positions 12705 and 16223 were observed with higher frequencies in healthy individuals than in colorectal cancer patients. Nevertheless, the differences of the R macrohaplogroup (as well as 12705 or 16223 alleles) frequencies between cases and controls were statistically insignificant after Bonferroni correction. Most of the non-R clades were of Asian and African origin, but none of them were prevalent in the control group. Moreover, neither mtDNA alleles nor haplogroups were associated with clinicopathological parameters of colorectal cancer patients.
Contrary to some previous reports, the findings of this study do not support the hypothesis that mitochondrial DNA variants contribute to inherited predisposition to colorectal cancer.
迄今为止，已发现几种核DNA变异与结直肠癌发病风险增加有关。尽管线粒体在致癌过程中发挥着重要作用，但对于可能参与该疾病的遗传性线粒体DNA突变却知之甚少。因此，本研究分析了整个线粒体基因组中的遗传性突变与结直肠癌之间的潜在关联。
利用为波兰结直肠癌患者和健康个体测定的200个有丝分裂基因组序列，研究线粒体DNA等位基因或单倍群与结直肠癌之间的关联。另外，为1353名波兰普通人群个体测定的线粒体DNA控制区单倍型，用于比较病例组和对照组之间的单倍群及某些等位基因频率。
在健康个体中观察到非R支系及其在12705和16223位点的诊断性T等位基因的频率高于结直肠癌患者。然而，经Bonferroni校正后，病例组和对照组之间R大分支（以及12705或16223等位基因）频率的差异无统计学意义。大多数非R支系起源于亚洲和非洲，但在对照组中均不常见。此外，线粒体DNA等位基因和单倍群均与结直肠癌患者的临床病理参数无关。
与之前的一些报道相反，本研究结果不支持线粒体DNA变异导致结直肠癌遗传性易感性的假说。
