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Cancer Epidemiol Biomarkers Prev. 2015 Mar;24(3):512-519. doi: 10.1158/1055-9965.EPI-14-1161. Epub 2015 Jan 13.

Association of the colorectal CpG island methylator phenotype with molecular features, risk factors, and family history.

Author information

1
USC Epigenome Center, University of Southern California, Los Angeles, CA.
2
Department of Biochemistry and Molecular Biology,University of Southern California, Los Angeles, CA, USA.
3
Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
4
Department of Surgery, University of Southern California, Los Angeles, CA, USA.
5
Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology.
6
Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, VIC, Australia.
7
Queensland Institute of Medical Research, Herston, QLD 4029, Australia.
8
Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI.
9
Department of Health Science Research, Mayo Clinic, Scottsdale, AZ, USA.
10
Department of Pathology and Laboratory Medicine, Samuel Lunenfield Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada.
11
Epidemiology Department, University of Washington and Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
12
Epidemiology Research Program, American Cancer Society, Atlanta, GA.
13
Division of Gastroenterology, University of Colorado School of Medicine, Denver, Colorado.
14
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
15
The Queen Elizabeth Hospital, Woodville, SA 5011, Australia.
#
Contributed equally

Abstract

BACKGROUND:

The CpG island methylator phenotype (CIMP) represents a subset of colorectal cancers characterized by widespread aberrant DNA hypermethylation at select CpG islands. The risk factors and environmental exposures contributing to etiologic heterogeneity between CIMP and non-CIMP tumors are not known.

METHODS:

We measured the CIMP status of 3,119 primary population-based colorectal cancer tumors from the multinational Colon Cancer Family Registry. Etiologic heterogeneity was assessed by a case-case study comparing risk factor frequency of colorectal cancer cases with CIMP and non-CIMP tumors using logistic regression to estimate the case-case odds ratio (ccOR).

RESULTS:

We found associations between tumor CIMP status and MSI-H (ccOR = 7.6), BRAF V600E mutation (ccOR = 59.8), proximal tumor site (ccOR = 9; all P < 0.0001), female sex [ccOR = 1.8; 95% confidence interval (CI), 1.5-2.1], older age (ccOR = 4.0 comparing over 70 years vs. under 50; 95% CI, 3.0-5.5), and family history of CRC (ccOR = 0.6; 95% CI, 0.5-0.7). While use of NSAIDs varied by tumor CIMP status for both males and females (P = 0.0001 and P = 0.02, respectively), use of multivitamin or calcium supplements did not. Only for female colorectal cancer was CIMP status associated with increased pack-years of smoking (Ptrend < 0.001) and body mass index (BMI; Ptrend = 0.03).

CONCLUSIONS:

The frequency of several colorectal cancer risk factors varied by CIMP status, and the associations of smoking and obesity with tumor subtype were evident only for females.

IMPACT:

Differences in the associations of a unique DNA methylation-based subgroup of colorectal cancer with important lifestyle and environmental exposures increase understanding of the molecular pathologic epidemiology of this heavily methylated subset of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 512-9. ©2015 AACR.

PMID:
25587051
PMCID:
PMC4355081
DOI:
10.1158/1055-9965.EPI-14-1161
[Indexed for MEDLINE]
Free PMC Article

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