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

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dc.contributor.authorWeisenberger, D.
dc.contributor.authorLevine, A.
dc.contributor.authorLong, T.
dc.contributor.authorBuchanan, D.
dc.contributor.authorWalters, R.
dc.contributor.authorClendenning, M.
dc.contributor.authorRosty, C.
dc.contributor.authorJoshi, A.
dc.contributor.authorStern, M.
dc.contributor.authorLe Marchand, L.
dc.contributor.authorLindor, N.
dc.contributor.authorDaftary, D.
dc.contributor.authorGallinger, S.
dc.contributor.authorSelander, T.
dc.contributor.authorBapat, B.
dc.contributor.authorNewcomb, P.
dc.contributor.authorCampbell, P.
dc.contributor.authorCasey, G.
dc.contributor.authorAhnen, D.
dc.contributor.authorBaron, J.
dc.contributor.authoret al.
dc.date.issued2015
dc.description.abstractBackground: 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.
dc.description.statementofresponsibilityD.J. Weisenberger ... J.P. Young et al. (for the Colon Cancer Family Registry)
dc.identifier.citationCancer Epidemiology, Biomarkers and Prevention, 2015; 24(3):512-519
dc.identifier.doi10.1158/1055-9965.EPI-14-1161
dc.identifier.issn1055-9965
dc.identifier.issn1538-7755
dc.identifier.orcidYoung, J. [0000-0002-1514-1522]
dc.identifier.urihttp://hdl.handle.net/2440/102025
dc.language.isoen
dc.publisherAmerican Association for Cancer Research
dc.rights© 2015 American Association for Cancer Research
dc.source.urihttps://doi.org/10.1158/1055-9965.epi-14-1161
dc.subjectHumans
dc.subjectColorectal Neoplasms
dc.subjectGenetic Predisposition to Disease
dc.subjectRisk Factors
dc.subjectDNA Methylation
dc.subjectCpG Islands
dc.subjectPhenotype
dc.subjectMiddle Aged
dc.subjectFamily Health
dc.titleAssociation of the colorectal CpG island methylator phenotype with molecular features, risk factors, and family history
dc.typeJournal article
pubs.publication-statusPublished

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