No association of CpG island methylator phenotype and colorectal cancer survival: population-based study.
BACKGROUND
Previous studies have shown adverse effects of CpG island methylator phenotype (CIMP) on colorectal cancer (CRC) prognosis. However, sample sizes were often limited and only few studies were able to adjust for relevant molecular features associated with CIMP. The aim of this study was to investigate the impact of CIMP on CRC survival in a large population-based study with comprehensive adjustment.


METHODS
The CIMP status and other molecular tumour features were analysed in 1385 CRC patients diagnosed between 2003 and 2010. Detailed information were obtained from standardised personal interviews and medical records. During follow-up (median: 4.9 years), we assessed vital status, cause of death and therapy details. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of survival after CRC.


RESULTS
The CIMP-H occurred more frequently in patients with older age, female gender, cancer in the proximal colon, BRAF mutation and microsatellite instability-high (MSI-H). However, CIMP status was not associated with CRC prognosis in CRC patients (HR=1.00; 95% CI=0.72-1.40 for overall survival; HR=0.96; 95% CI=0.65-1.41 for disease-specific survival) or in any of the subgroups. Although CIMP status was associated with the presence of MSI-H and BRAF mutation, the prognostic effects of MSI-H (HR=0.49; 95% CI=0.27-0.90) and BRAF mutation (HR=1.78; 95% CI=1.10-2.84) were independent of CIMP status. Similar benefit of chemotherapy was found for CRC outcomes in both the CIMP-low/negative group and the CIMP-high group.


CONCLUSIONS
CpG island methylator phenotype was not associated with CRC prognosis after adjusting for other important clinical factors and associated mutations.
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Min
M
Jia
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Lina
L
Jansen
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Viola
V
Walter
Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany.|Institute of Pathology, University Medical Center Mainz, 55131 Mainz, Germany.
Katrin
K
Tagscherer
Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany.|Institute of Pathology, University Medical Center Mainz, 55131 Mainz, Germany.
Wilfried
W
Roth
Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany.|NCT Tissue Bank, National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany.
Esther
E
Herpel
Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
Matthias
M
Kloor
Institute of Pathology, Charité University Medicine, 10117 Berlin, Germany.
Hendrik
H
Bläker
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Jenny
J
Chang-Claude
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.|Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany.|German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Hermann
H
Brenner
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Michael
M
Hoffmeister
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016019:Survival Analysis
D000970:Antineoplastic Agents