TY - JOUR
T1 - Tumor LINE-1 methylation level and colorectal cancer location in relation to patient survival
AU - Mima, Kosuke
AU - Nowak, Jonathan A.
AU - Qian, Zhi Rong
AU - Cao, Yin
AU - Song, Mingyang
AU - Masugi, Yohei
AU - Shi, Yan
AU - da Silva, Annacarolina
AU - Gu, Mancang
AU - Li, Wanwan
AU - Hamada, Tsuyoshi
AU - Zhang, Xuehong
AU - Wu, Kana
AU - Meyerhardt, Jeffrey A.
AU - Baba, Hideo
AU - Giovannucci, Edward L.
AU - Chan, Andrew T.
AU - Fuchs, Charles S.
AU - Ogino, Shuji
AU - Nishihara, Reiko
PY - 2016
Y1 - 2016
N2 - Colorectal tumors arise with genomic and epigenomic alterations through interactions between neoplastic cells, immune cells, and microbiota that vary along the proximal to distal axis of colorectum. Long interspersed nucleotide element-1 (LINE-1) hypomethylation in colorectal cancer has been associated with worse clinical outcome. Utilizing 1,317 colon and rectal carcinoma cases in two U.S.-nationwide prospective cohort studies, we examined patient survival according to LINE-1 methylation level stratified by tumor location. Cox proportional hazards model was used to assess a statistical interaction between LINE-1 methylation level and tumor location in colorectal cancer-specific mortality analysis, controlling for potential confounders including microsatellite instability, CpG island methylator phenotype, and KRAS, BRAF, and PIK3CA mutations. A statistically significant interaction was found between LINE-1 methylation level and tumor location in colorectal cancer-specific mortality analysis (Pinteraction = 0.011). The association of LINE-1 hypomethylation with higher colorectal cancer-specific mortality was stronger in proximal colon cancers (multivariable hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.21 to 2.28) than in distal colon cancers (multivariable HR, 1.18; 95% CI, 0.81 to 1.72) or rectal cancers (multivariable HR, 0.87; 95% CI, 0.57 to 1.34). Our data suggest the interactive effect of LINE-1 methylation level and colorectal cancer location on clinical outcome.
AB - Colorectal tumors arise with genomic and epigenomic alterations through interactions between neoplastic cells, immune cells, and microbiota that vary along the proximal to distal axis of colorectum. Long interspersed nucleotide element-1 (LINE-1) hypomethylation in colorectal cancer has been associated with worse clinical outcome. Utilizing 1,317 colon and rectal carcinoma cases in two U.S.-nationwide prospective cohort studies, we examined patient survival according to LINE-1 methylation level stratified by tumor location. Cox proportional hazards model was used to assess a statistical interaction between LINE-1 methylation level and tumor location in colorectal cancer-specific mortality analysis, controlling for potential confounders including microsatellite instability, CpG island methylator phenotype, and KRAS, BRAF, and PIK3CA mutations. A statistically significant interaction was found between LINE-1 methylation level and tumor location in colorectal cancer-specific mortality analysis (Pinteraction = 0.011). The association of LINE-1 hypomethylation with higher colorectal cancer-specific mortality was stronger in proximal colon cancers (multivariable hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.21 to 2.28) than in distal colon cancers (multivariable HR, 1.18; 95% CI, 0.81 to 1.72) or rectal cancers (multivariable HR, 0.87; 95% CI, 0.57 to 1.34). Our data suggest the interactive effect of LINE-1 methylation level and colorectal cancer location on clinical outcome.
KW - Epigenetics
KW - Left-sided
KW - Molecular pathological epidemiology
KW - Prognosis
KW - Right-sided
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UR - http://www.scopus.com/inward/citedby.url?scp=84983479239&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.10398
DO - 10.18632/oncotarget.10398
M3 - Article
C2 - 27391152
AN - SCOPUS:84983479239
SN - 1949-2553
VL - 7
SP - 55098
EP - 55109
JO - Oncotarget
JF - Oncotarget
IS - 34
ER -
