title: Association of the colorectal CpG island methylator phenotype with molecular features, risk factors, and family history.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: USC Epigenome Center, University of Southern California, Los Angeles, CA.|Department of Biochemistry and Molecular Biology,University of Southern California, Los Angeles, CA, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisenberger
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: A Joan
authors.initials: AJ
authors.lastname: Levine
authors.affiliation: Department of Surgery, University of Southern California, Los Angeles, CA, USA.
authors.forename: Tiffany I
authors.initials: TI
authors.lastname: Long
authors.affiliation: Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology.|Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Buchanan
authors.affiliation: Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology.
authors.forename: Rhiannon
authors.initials: R
authors.lastname: Walters
authors.affiliation: Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology.
authors.forename: Mark
authors.initials: M
authors.lastname: Clendenning
authors.affiliation: Queensland Institute of Medical Research, Herston, QLD 4029, Australia.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rosty
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Amit D
authors.initials: AD
authors.lastname: Joshi
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Stern
authors.affiliation: Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI.
authors.forename: Loic
authors.initials: L
authors.lastname: LeMarchand
authors.affiliation: Department of Health Science Research, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.affiliation: Department of Pathology and Laboratory Medicine, Samuel Lunenfield Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Darshana
authors.initials: D
authors.lastname: Daftary
authors.affiliation: Department of Pathology and Laboratory Medicine, Samuel Lunenfield Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.affiliation: Department of Pathology and Laboratory Medicine, Samuel Lunenfield Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Teresa
authors.initials: T
authors.lastname: Selander
authors.affiliation: Department of Pathology and Laboratory Medicine, Samuel Lunenfield Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Bharati
authors.initials: B
authors.lastname: Bapat
authors.affiliation: Epidemiology Department, University of Washington and Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, GA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Campbell
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.affiliation: Division of Gastroenterology, University of Colorado School of Medicine, Denver, Colorado.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Ahnen
authors.affiliation: Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.affiliation: Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: Queensland Institute of Medical Research, Herston, QLD 4029, Australia.|The Queen Elizabeth Hospital, Woodville, SA 5011, Australia.
authors.forename: Joanne P
authors.initials: JP
authors.lastname: Young
authors.affiliation: USC Epigenome Center, University of Southern California, Los Angeles, CA.|Department of Biochemistry and Molecular Biology,University of Southern California, Los Angeles, CA, USA.|Department of Surgery, University of Southern California, Los Angeles, CA, USA.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Laird
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Siegmund
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors