Tumor long interspersed nucleotide element-1 (LINE-1) hypomethylation in relation to age of colorectal cancer diagnosis and prognosis
Akimoto, Naohiko; Zhao, Melissa; Ugai, Tomotaka; Zhong, Rong; Lau, Mai Chan; Fujiyoshi, Kenji; Kishikawa, Junko; Haruki, Koichiro; Arima, Kota; Twombly, Tyler S.; Zhang, Xuehong; Giovannucci, Edward L.; Wu, Kana; Song, Mingyang; Chan, Andrew T.; Cao, Yin; Meyerhardt, Jeffrey A.; Ng, Kimmie; Giannakis, Marios; Väyrynen, Juha P.; Nowak, Jonathan A.; Ogino, Shuji (2021-04-22)
Akimoto, N.; Zhao, M.; Ugai, T.; Zhong, R.; Lau, M.C.; Fujiyoshi, K.; Kishikawa, J.; Haruki, K.; Arima, K.; Twombly, T.S.; Zhang, X.; Giovannucci, E.L.; Wu, K.; Song, M.; Chan, A.T.; Cao, Y.; Meyerhardt, J.A.; Ng, K.; Giannakis, M.; Väyrynen, J.P.; Nowak, J.A.; Ogino, S. Tumor Long Interspersed Nucleotide Element-1 (LINE-1) Hypomethylation in Relation to Age of Colorectal Cancer Diagnosis and Prognosis. Cancers 2021, 13, 2016. https://doi.org/10.3390/cancers13092016
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https://urn.fi/URN:NBN:fi-fe2021060935925
Tiivistelmä
Abstract
Evidence indicates the pathogenic role of epigenetic alterations in early-onset colorectal cancers diagnosed before age 50. However, features of colorectal cancers diagnosed at age 50–54 (hereafter referred to as “intermediate-onset”) remain less known. We hypothesized that tumor long interspersed nucleotide element-1 (LINE-1) hypomethylation might be increasingly more common with decreasing age of colorectal cancer diagnosis. In 1356 colorectal cancers, including 28 early-onset and 66 intermediate-onset cases, the tumor LINE-1 methylation level measured by bisulfite-PCR-pyrosequencing (scaled 0 to 100) showed a mean of 63.6 (standard deviation (SD) 10.1). The mean tumor LINE-1 methylation level decreased with decreasing age (mean 64.7 (SD 10.4) in age ≥70, 62.8 (SD 9.4) in age 55–69, 61.0 (SD 10.2) in age 50–54, and 58.9 (SD 12.0) in age <50; p < 0.0001). In linear regression analysis, the multivariable-adjusted β coefficient (95% confidence interval (CI)) (vs. age ≥70) was −1.38 (−2.47 to −0.30) for age 55–69, −2.82 (−5.29 to −0.34) for age 50–54, and −4.54 (−8.24 to −0.85) for age <50 (Ptrend = 0.0003). Multivariable-adjusted hazard ratios (95% CI) for LINE-1 methylation levels of ≤45, 45–55, and 55–65 (vs. >65) were 2.33 (1.49–3.64), 1.39 (1.05–1.85), and 1.29 (1.02–1.63), respectively (Ptrend = 0.0005). In conclusion, tumor LINE-1 hypomethylation is increasingly more common with decreasing age of colorectal cancer diagnosis, suggesting a role of global DNA hypomethylation in colorectal cancer arising in younger adults.
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