TY - JOUR
T1 - Tumor long interspersed nucleotide element-1 (LINE-1) hypomethylation in relation to age of colorectal cancer diagnosis and prognosis
AU - Akimoto, Naohiko
AU - Zhao, Melissa
AU - Ugai, Tomotaka
AU - Zhong, Rong
AU - Lau, Mai Chan
AU - Fujiyoshi, Kenji
AU - Kishikawa, Junko
AU - Haruki, Koichiro
AU - Arima, Kota
AU - Twombly, Tyler S.
AU - Zhang, Xuehong
AU - Giovannucci, Edward L.
AU - Wu, Kana
AU - Song, Mingyang
AU - Chan, Andrew T.
AU - Cao, Yin
AU - Meyerhardt, Jeffrey A.
AU - Ng, Kimmie
AU - Giannakis, Marios
AU - Väyrynen, Juha P.
AU - Nowak, Jonathan A.
AU - Ogino, Shuji
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - 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-PCRpyrosequencing (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.
AB - 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-PCRpyrosequencing (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.
KW - Carcinogenesis
KW - Colorectal neoplasms
KW - Epigenomics
KW - Genomic instability
KW - Long interspersed nuclear element
KW - Molecular pathology
KW - Retrotransposon
KW - Screening
KW - Transposable element
KW - Youngonset cancer
UR - http://www.scopus.com/inward/record.url?scp=85104501489&partnerID=8YFLogxK
U2 - 10.3390/cancers13092016
DO - 10.3390/cancers13092016
M3 - Article
C2 - 33922024
AN - SCOPUS:85104501489
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 9
M1 - 2016
ER -