OR14: The Colon Cancer Family Registry Cohort and genetic factors for colorectal cancer

Mark A. Jenkins1, Daniel D. Buchanan,1,2 Aung K. Win,1 Noralane M. Lindor,3 Steven Gallinger,4 Loic Le Marchand,5 Graham Casey,6 Polly A. Newcomb,7,8 Robert W. Haile,9 John A. Baron,10 John D. Potter,7,8,11 Finlay A. Macrae,12 Stephen N. Thibodeau,13 John L. Hopper,1 Allyson Templeton7 for the Colon Cancer Family Registry.

1. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia. 2. Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia. 3. Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, Arizona, USA. 4. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. 5. University of Hawaii Cancer Center, Honolulu, Hawaii, USA. 6. Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA. 7. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. 8. School of Public Health, University of Washington, Seattle, Washington, USA. 9. Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, California, USA. 10. Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA. 11. Centre for Public Health Research, Massey University, Wellington, New Zealand. 12. Colorectal Cancer Genetics, Royal Melbourne Hospital, Parkville, Victoria, Australia. 13. Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.


To investigate the genetic and environmental aetiology of colorectal cancer, the National Institutes of Health (USA) have funded (since 1997) the Colon Cancer Family Registry, which is a consortium of six institutions in Australia, Canada and the USA that have recruited approximately 13,000 population- and clinic-based colorectal cancer and control families comprising approximately 38,000 participants.  Participants have completed a baseline risk factor questionnaire, donated a blood sample, and given permission to access medical records, and every 5-years have completed a follow-up questionnaire.  Participants have undergone tumour testing for mismatch repair proficiency and germline testing for variants in mismatch repair (MMR) genes and MUTYH, as well as whole exome and whole genome sequencing and genome-wide SNP testing.


Cancer risks for carriers of germline mutations in MMR genes and MUTYH have been estimated using modified segregation analyses, conditioning on the ascertainment.  Modifiers of cancer risk for MMR gene and MUTYH carriers have been studied using lifestyle factors, personal characteristics and genetic factors. Risk of metachronous cancer in Lynch syndrome has been estimated. Studies on characterisation of MMR gene variants, methods of variant detection and psychological impact of testing have been conducted. Population prevalence of mutations in each of the four MMR genes and MUTYH have been estimated, as has the proportion of MMR gene mutation carriers that are de novo. Gene discovery for colorectal cancer has been conducted using sequencing utilising the family design and conducted using genome-wide association studies utilising the case-control design.


The Colon Cancer Family Registry comprises 2,103 confirmed carriers of a germline MMR mutation, 382 monoallelic carriers and 54 biallelic carriers in MUTYH.

Families 278 339 101 55 8 264 1045
Carriers 769 964 234 107 29 436* 2539

*includes 382 monoallelic and 54 biallelic carriers

Over 450 participants from 260 families have undergone whole exome or whole genome sequencing. Approximately 10,000 cases and controls have undergone genome-wide SNP testing. Over 120 studies on Lynch syndrome, 12 studies on MUTYH, and over 120 studies on other genetic factors for colorectal cancer have been published using the Colon Cancer Family Registry resource. https://coloncfr.org/publications. The resource is available, on application to investigators and has been utilised for over 300 projects (83 from investigators external to the Colon Cancer Family Registry).  Policies and instructions for application to collaborate and access data, DNA or other biospecimens have been developed and are available at http://coloncfr.org/collaboration


The Colon Cancer Family Registry is a large and well-characterised (in terms of genetic risk factors) prospective series of colorectal cancer cases and controls that includes detailed information on family history of cancer and recruitment of relatives.  The resource has been used for many research studies on genetic syndromes for colorectal cancer including Lynch syndrome and MUTYH.

Funding source: This work was supported by grant UM1 CA167551 from the National Cancer Institute, National Institutes of Health (NIH) and through cooperative agreements with members of the Colon Cancer Family Registry (CFR) and Principal Investigators. Collaborating centers include Australasian Colorectal Cancer Family Registry (U01/U24 CA097735), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01/U24 CA074800), Ontario Familial Colorectal Cancer Registry (U01/U24 CA074783), Seattle Colorectal Cancer Family Registry (U01/U24 CA074794), Stanford Consortium Colorectal Cancer Family Registry (U01/U24 CA074799), and University of Hawaii Colorectal Cancer Family Registry (U01/U24 CA074806).