Devall Matthew A, Sun Xiangqing, Eaton Stephen, Cooper Gregory S, Willis Joseph E, Weisenberger Daniel J, Casey Graham, Li Li
Department of Family Medicine, University of Virginia, Charlottesville, VA 22903, USA.
Department of Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH 44106, USA.
Cancers (Basel). 2022 Dec 22;15(1):45. doi: 10.3390/cancers15010045.
Approximately 90% of colorectal cancer (CRC) develop over the age of 50, highlighting the important role of aging in CRC risk. African Americans (AAs) shoulder a greater CRC burden than European Americans (EA) and are more likely to develop CRC at a younger age. The effects of aging in AA and EA normal rectal tissue have yet to be defined. Here, we performed epigenome-wide DNA methylation analysis in the first, large-scale biracial cohort of normal rectum ( = 140 samples). We identified increased epigenetic age acceleration in EA than AA rectum ( = 3.91 × 10) using linear regression. We also identified differentially methylated regions (DMRs) associated with chronological aging in AA and EA, separately using DMRcate. Next, a consensus set of regions associated with cancer was identified through DMR analysis of two rectal cancer cohorts. The vast majority of AA DMRs were present in our analysis of aging in rectum of EA subjects, though rates of epigenetic drift were significantly greater in AA ( = 1.94 × 10). However, 3.66-fold more DMRs were associated with aging in rectum of EA subjects, many of which were also associated with rectal cancer. Our findings reveal a novel relationship between race, age, DNA methylation and rectal cancer risk that warrants further investigation.
约90%的结直肠癌（CRC）在50岁以上发病，这凸显了衰老在CRC风险中的重要作用。非裔美国人（AAs）比欧裔美国人（EAs）承担着更大的CRC负担，且更有可能在年轻时患CRC。衰老对AAs和EAs正常直肠组织的影响尚未明确。在此，我们在首个大规模双种族正常直肠队列（n = 140个样本）中进行了全表观基因组DNA甲基化分析。通过线性回归，我们发现EAs直肠的表观遗传年龄加速比AAs更高（p = 3.91 × 10⁻⁴）。我们还分别使用DMRcate鉴定了与AAs和EAs按时间顺序衰老相关的差异甲基化区域（DMRs）。接下来，通过对两个直肠癌队列的DMR分析，确定了一组与癌症相关的共识区域。在我们对EAs受试者直肠衰老的分析中，绝大多数AAs的DMRs都存在，尽管AAs的表观遗传漂变率显著更高（p = 1.94 × 10⁻⁴）。然而，与EAs受试者直肠衰老相关的DMRs数量是AAs的3.66倍，其中许多也与直肠癌相关。我们的发现揭示了种族、年龄、DNA甲基化与直肠癌风险之间的一种新关系，值得进一步研究。
