Tumor LINE-1 methylation level and colorectal cancer location in relation to patient survival
Metrics: PDF 2425 views | HTML 3273 views | ?
Kosuke Mima1,*, Jonathan A. Nowak2,*, Zhi Rong Qian1,*, Yin Cao3,4,5, Mingyang Song3,4,5, Yohei Masugi1, Yan Shi1, Annacarolina da Silva1, Mancang Gu1, Wanwan Li1, Tsuyoshi Hamada1, Xuehong Zhang6, Kana Wu5,6, Jeffrey A. Meyerhardt1, Hideo Baba7, Edward L. Giovannucci5,6,8, Andrew T. Chan3,4,6,*, Charles S. Fuchs1,6,*, Shuji Ogino1,2,8,*, Reiko Nishihara1,5,*
1Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
2Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
3Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
4Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
5Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
6Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
7Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
8Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
*These authors have contributed equally to this work
Shuji Ogino, email: [email protected]
Reiko Nishihara, email: [email protected]
Keywords: epigenetics, left-sided, molecular pathological epidemiology, prognosis, right-sided
Received: January 30, 2016 Accepted: June 17, 2016 Published: July 04, 2016
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.