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Study Description

The Colon Cancer Family Registry Cohort (CCFRC www.coloncfr.org) is a cohort of families recruited through six study sites located in the USA, Canada, Australia, and New Zealand. The CCFRC was formed as a resource to support studies on the etiology, prevention, and clinical management of colorectal cancer. Recruitment protocols fall broadly into two main categories: population-based and clinic-based ascertainment. Between 1998 and 2013, the CCFR recruited and interviewed probands who were either recently diagnosed with colorectal cancer that was reported to state or regional population cancer registries in the United States (Washington, California, Arizona, Minnesota, Colorado, New Hampshire, North Carolina, and Hawaii), Australia (Victoria), and Canada (Ontario) or were from multiple-case families referred to family-cancer clinics in the United States (Mayo Clinic in Rochester, Minnesota, and Cleveland Clinic in Cleveland, Ohio), Australia (Melbourne, Adelaide, Perth, Brisbane, and Sydney), New Zealand (Auckland), and Canada. Cases with known familial adenomatous polyposis were excluded. Once recruited, probands were asked for permission to contact their relatives for recruitment. Collectively, we have enrolled 42,49874 participants in 15,048 families who participated in standardized protocols used to collect information regarding family cancer history and colorectal cancer risk factors and biospecimens. All participants of population-based case families (excluding control-families) and clinic-based families are asked to provide updates on their personal and family history of cancer as well as their history of surgery, cancer screening, and some risk factors every 4-5 years either by telephone interview or by self-completed questionnaire via mail or online (PMID: 17982118).

  • Study Weblinks:
  • Study Design:
    • Case-Control
  • Study Type:
    • Case-Control
    • Cohort
    • Collection
    • Epigenetics
    • Extended Pedigrees
    • Family
    • Genotype
    • Genotype/Expression
    • GWAS
    • Individual-Level Genomic Data
    • Multicenter
    • Multiplex Families
    • Observational
    • Probands
    • Prospective
    • Tissue Expression
    • Tumor
    • Tumor vs. Matched-Normal
  • Total number of consented subjects: 38362
  • Subject Sample Telemetry Report (SSTR)
Authorized Access
Publicly Available Data
  Link to other NCBI resources related to this study
Study Inclusion/Exclusion Criteria

In general, participant recruitment took place over three 5-year “phases” (Phase I: 1998-2003; Phase II: 2003-2008; Phase III: 2008-2013) using two ascertainment strategies: population-based and clinic-based.

Phase I Population-Based Recruitment: All six Colon CFR centers enrolled families with incident colorectal cancer identified through population-based cancer registries in defined geographic areas. Sampling probabilities differed according to age at diagnosis, race, and/or family history of colorectal cancer, depending on CCFR site.

Phase I Clinic-Based Recruitment: Three centers recruited families with multiple or early-onset cases of colorectal cancer through clinical settings: Mayo Clinic, USC (Cleveland Clinic), and Australia (seven family cancer clinics across Australia and New Zealand). Clinic-based probands, defined as the first family member enrolled in the CCFR, may or may not have had a personal history of colorectal cancer. Instead, eligibility was based on one or more of the following criteria: two or more relatives with a personal history of colorectal cancer or Lynch syndrome cancer, a proband diagnosed with colorectal cancer at a young age, or a proband presenting at a clinic with Lynch syndrome or Lynch-like syndrome.

Phase II Population-Based Recruitment: Recruitment targeted certain subgroups including: a) families with possible MMR mutations, including those cases with incident colorectal cancer diagnosed under the age of 50 years (all centers) and/or families with multiple cases of colorectal cancer (Mayo Clinic) or b) families from specific racial and ethnic groups. Enhanced recruitment of Japanese Americans (UHI and UCSF (subsite to UHI)) and African Americans (USC, UNC (subsite to USC) and UCSF) was funded under a separate R01 grant from 2004-2009.

Phase II Clinic-Based Recruitment: The Ontario site began recruiting clinic-based families from across Canada, while Mayo Clinic, USC (Cleveland Clinic), and Australasia continued clinic-based recruitment through cancer family clinics.

Phase III Clinic-Based Recruitment: All sites except Hawaii recruited additional families through family cancer and/or genetic clinics. Selection criteria were site-specific, but included specific high-risk criteria (e.g., family history meeting Amsterdam I criteria, known or suspected MYH or MMR mutation carriers). In addition, additional family members in existing high-risk families were recruited.

Study History

1998-2003: Phase I recruitment/enrollment. Data and specimen collection included: baseline epidemiologic/risk factor questionnaires, diet questionnaires, blood or buccal samples, baseline colorectal cancer tumor blocks (FFPE and limited fresh frozen). Testing: FFPE colorectal cancer tumors were tested for microsatellite instability (MSI) and MMR expression (via IHC). Germline testing was performed for MMR and MYH gene mutations as indicated.

2003-2008: Phase II recruitment/enrollment and follow-up. Data and specimen collection included: baseline epidemiologic/risk factor questionnaires, diet questionnaires (UHI and UCSF (sub-site to UHI)), blood or buccal samples, baseline colorectal cancer tumor blocks (FFPE and limited fresh frozen). The first 5-year epidemiologic/risk factors follow-up questionnaires were administered to Phase I enrollees (excluding population-based controls). Testing: FFPE colorectal cancer tumors were tested for MMR expression (via IHC). Germline testing was performed for MMR and MYH gene mutations as indicated. Family members were tested for the family mutation for cases with a deleterious mutation in an MMR and/or MYH gene. SNP (Affymetrix Human Mapping 100k & 500k arrays) and CpG Methylation (HumanMethylation450 array) testing was performed on population-based case and control participants from the Ontario site (OFCCR). In addition, SNP genotyping (Illumina Human1M v1 and/or Illumina Human 1M-Duo) was performed on a subset of non-Hispanic White population-based case and control participants from the Australia, Ontario, and Seattle CCFR sites.

2008-2013: Phase III recruitment/enrollment and follow-up. Data and specimen collection included: baseline epidemiologic/risk factor questionnaires, blood or buccal samples, baseline colorectal cancer FFPE tumor blocks. The second 5-year epidemiologic/risk factors follow-up questionnaires were administered to Phase I enrollees and the first to Phase II enrollees. Testing: FFPE colorectal cancer tumors were tested for MMR expression (via IHC), BRAF and KRAS mutation, MLH1 promoter methylation as indicated. Germline testing for MMR and MYH gene mutations was performed as indicated. SNP genotyping (Illumina HumanOmni1-Quad) was performed on of non-Hispanic White population-based case and family control participants from all sites.

2013-2018: Phase IV follow-up. Follow-up included the third 5-year epidemiologic/risk factors follow-up questionnaire completion of Phase I enrollees, the second for Phase II enrollees, and the first for Phase III enrollees (excluding population-based spouse controls). Tumor molecular characterization for tumor MMR status, BRAF, and KRAS mutations was completed on all incident colorectal cancers, followed by germline MMR and MYH testing as indicated. Family members were tested for the family mutation for cases with a deleterious mutation in an MMR and/or MYH gene. SNP genotyping was performed on colorectal cancer case and control participants (not previously genotyped) of European descent on one of two platforms: 1) CORECT Affymetrix Axiom, or 2) CORECT OncoArray-500k_C array.

2018-present: Phase V follow-up: follow-up included the fourth 5-year epidemiologic/risk factors follow-up questionnaire completion of Phase I enrollees, the third for Phase II enrollees, and the second for Phase III enrollees. Tumor molecular characterization for tumor MMR status, BRAF, and KRAS mutations was completed on all incident colorectal cancers and tumor MLH1 methylation testing was completed as indicated via IHC. Germline MMR and MYH testing for incident colorectal cancer case participants as indicated. Family members were tested for the family mutation for case participants with a deleterious mutation in an MMR and/or MYH gene.


Selected Publications
Diseases/Traits Related to Study (MeSH terms)
Links to Related Genes
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See articles in PMC citing this study accession
Study Attribution
  • Principal Investigators
    • Jane A. Figueiredo. Cedars-Sinai Medical Center, Los Angeles, CA, USA.
    • Steven Gallinger. Cancer Care Ontario, Toronto, Ontario, Canada; Mount Sinai Hospital, Toronto, Ontario, Canada; University Health Network, Toronto, Ontario, Canada.
    • Robert W. Haile. University of Southern California, Los Angeles, CA, USA; Stanford University, Stanford, CA, USA; Cedars-Sinai Medical Center, Los Angeles, CA, USA.
    • John L. Hopper. University of Melbourne, Melbourne, Victoria, AS.
    • Jeremy R. Jass. Queensland University of Technology, Brisbane, Queensland, AS.
    • Mark A. Jenkins. University of Melbourne, Melbourne, Victoria, AS.
    • Loic Le Marchand. University Of Hawaii at Manoa, Honolulu, HI, USA.
    • Noralane M. Lindor. Mayo Clinic, Rochester, MN, USA; Mayo Clinic, Phoenix, AZ, USA.
    • Polly A. Newcomb. Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
    • Rish K. Pai. Mayo Clinic, Phoenix, AZ, USA.
    • Amanda I. Phipps. Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
    • John D. Potter. Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
    • Steven N. Thibodeau. Mayo Clinic, Rochester, MN, USA.
  • Funding Sources
    • U01 CA167551. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • UM1 CA167551. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • U01 CA044778. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • U01 CA074783. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • U24 CA074783. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • U01 CA074799. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • U24 CA074799. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • U01 CA097735. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • U24 CA097735. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • U01 CA074806. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • U24 CA074806. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • U01 CA074800. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • U24 CA074800. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • U01 CA074794. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • U24 CA074794. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • R01 CA104132. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • R01 CA118699. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    • R01 CA076366. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.