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Type: Journal article
Title: Association of the colorectal CpG island methylator phenotype with molecular features, risk factors, and family history
Author: Weisenberger, D.
Levine, A.
Long, T.
Buchanan, D.
Walters, R.
Clendenning, M.
Rosty, C.
Joshi, A.
Stern, M.
Le Marchand, L.
Lindor, N.
Daftary, D.
Gallinger, S.
Selander, T.
Bapat, B.
Newcomb, P.
Campbell, P.
Casey, G.
Ahnen, D.
Baron, J.
et al.
Citation: Cancer Epidemiology, Biomarkers and Prevention, 2015; 24(3):512-519
Publisher: American Association for Cancer Research
Issue Date: 2015
ISSN: 1055-9965
Statement of
D.J. Weisenberger ... J.P. Young et al. (for the Colon Cancer Family Registry)
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.
Keywords: Humans
Colorectal Neoplasms
Genetic Predisposition to Disease
Risk Factors
DNA Methylation
CpG Islands
Middle Aged
Family Health
Rights: © 2015 American Association for Cancer Research
DOI: 10.1158/1055-9965.EPI-14-1161
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