Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
Department of Family Medicine, University of Virginia, Charlottesville, VA, USA.
J Natl Cancer Inst. 2021 Nov 29;113(12):1779-1782. doi: 10.1093/jnci/djaa206.
There are well-documented racial differences in age-of-onset and laterality of colorectal cancer. Epigenetic age acceleration is postulated to be an underlying factor. However, comparative studies of side-specific colonic tissue epigenetic aging are lacking. Here, we performed DNA methylation analysis of matched right and left biopsies of normal colon from 128 individuals. Among African Americans (n = 88), the right colon showed accelerated epigenetic aging as compared with individual-matched left colon (1.51 years; 95% confidence interval [CI] = 0.62 to 2.40 years; 2-sided P = .001). In contrast, among European Americans (n = 40), the right colon shows remarkable age deceleration (1.93 years; 95% CI = 0.65 to 3.21 years; 2-sided P = .004). Further, epigenome-wide analysis of DNA methylation identifies a unique pattern of hypermethylation in African American right colon. Our study is the first to report such race and side-specific differences in epigenetic aging of normal colon, providing novel insight into the observed younger age-of-onset and relative preponderance of right-side colon neoplasia in African Americans.
结直肠癌的发病年龄和侧别存在明显的种族差异，这一点已有充分的文献记载。据推测，表观遗传年龄加速是一个潜在的因素。然而，目前缺乏针对侧别特异性结肠组织表观遗传衰老的比较研究。在此，我们对 128 名个体的正常结肠配对的右、左侧活检进行了 DNA 甲基化分析。在非裔美国人（n=88）中，右半结肠的表观遗传衰老速度快于个体匹配的左半结肠（1.51 岁；95%置信区间[CI]：0.62 岁至 2.40 岁；双侧 P=0.001）。相比之下，在欧洲裔美国人（n=40）中，右半结肠表现出显著的年龄减速（1.93 岁；95%CI：0.65 岁至 3.21 岁；双侧 P=0.004）。此外，对 DNA 甲基化的全基因组分析鉴定出非裔美国人右半结肠存在独特的过度甲基化模式。本研究首次报道了正常结肠在表观遗传衰老方面的这种种族和侧别特异性差异，为观察到的非裔美国人结直肠癌发病年龄更小、右侧结肠肿瘤相对更为多见的现象提供了新的见解。
