POPULATION-BASED RECRUITMENT
CFR Site
Ascertainment Source / Phase I
(1997 – 2002) / Phase II
(2002 - 2007)
U of Hawaii
SEER Registry for State of Hawaii / Case criteria: Diagnosed in the state of Hawaii 1997-2001 with an adenocarcinoma of the colon or rectumbetween 18-84 years of age.
Selection criteria: 100% multiple-case families (≥ 1first-degree relatives with CRC) (no single-case families) were recruited.
Relative recruitment: Living parents, siblings andchildren of probands and affected relatives were recruited. In families with ≥ 3 CRC cases, distant affected and unaffected relatives (2nd/3rddegree) were recruited.
Control recruitment: Living, unaffected spouse of CRC affected participant recruited as a control if 18 years or older. / Case-1 criteria: Diagnosed in the state of Hawaii between 2002-2007with an adenocarcinoma of the colon or rectumbetween 18-49 years of age.
Selection criteria: 100%.
Relative recruitment: All living first-degree relatives of cases were recruited.
Control recruitment: Case spouses unaffected with CRC.
Case-2 criteria: Japanese-Am. diagnosed in the state of Hawaii between 2002-2007 with an adenocarcinoma of colon or rectumbetween 50-84 years of age.
Selection criteria: 100%.
Relative recruitment: Living parents, affected siblings, at least 1 unaffected sibling, were recruited.
Control recruitment: Case spouses unaffected with CRC.
Mayo Clinic
Minnesota Cancer Surveillance System (MCSS) (split 50/50 with USC) / Case criteria: Diagnosed in the state of Minnesota 1997- 2000 with CRC at18-74 years of age.
Selection-1 criteria: 100% cases in multiple living-case families (case has ≥ 2 living CRC-affected family members) were recruited.
Relative recruitment: All living FDR (adult children w/ cancer, any relative w/CRC, along with spouses and parents. Second-degree relatives from cancer side of family (grandparents, aunts/uncles).
Selection-2 criteria: 100% cases diagnosed 50 years of age (no family history eligibility criteria).
Relative recruitment: Both parents, up to 4 siblings (same sex, older) any relative w/CRC along with living spouses and parents were recruited.
Selection-3 criteria: 33% random sample of all cases until 200 total probands ascertained in this way have been recruited.
Control recruitment: Living, unaffected spouse of CRC affected participant recruited as a control if 18 years or older / Case criteria: Diagnosed in the state of Minnesota 2002-2007 with CRC.
Selection-1 criteria: 100% of cases diagnosed 50 years (no family hx criteria)
Relative recruitment: Both parents, living sibs with cancer, 2 unaffected siblings were recruited.
Selection-2 criteria: 100% of cases diagnosed at 51-74 years of age in families with ≥3 CRC-affected cases (≥ 2 of which are living and ≥ 2 are 1st degree, or a living CRC-affected sibling-pair).
Relative recruitment: Both parents, grandparents & aunts/uncles from cancer side. Siblings with any cancer, up to 2 unaffected siblings, adult children with cancer, any relative with CRC.
Selection-3 criteria: 100% sib pair cases (no family history eligibility criteria)
Relative recruitment: Both parents, living sibs with cancer, 2 unaffected sibs were recruited.
Control recruitment: Controls were not recruited.
USC Consortium
LA County Cancer Surveillance Program
Cancer Registries in: Arizona, Colorado, Minnesota (split 50/50 with Mayo), New Hampshire, University of North Carolina / Case criteria: Diagnosed in either LA County or Arizona, Colorado, Minnesota, and New Hampshire states, or one of the 33 North Carolina counties 1997 (1996 in Colorado)-1999 with incident CRC at 21-75 years of age.
Selection criteria:
- Screened: 33% Caucasian whites >50 yrs, 66% Caucasian whites <50 yrs, 66% minorities between the ages of 21 and 75.
- Of cases screened, recruited 100% of multiple-case families, and 16% of single-case families. Selected CRC-affected and unaffected family members (to 3rd degree) were recruited.
Control recruitment: Controls were not recruited / Case-1 criteria: African- or Japanese-American cases diagnosed in LA County (LA SEER) between 2002-2006 with incident CRC at 21-75 years of age.
Selection criteria: 100% of cases
Relative recruitment: Selected FDRs in families with 3 cases of CRC and all living FDRs in families with 3 cases of CRC
Case-2 criteria: African-American cases diagnosed in one of 38 North Carolina counties between 2002-2006 with incident CRC at 21-75 years of age.
Selection criteria: 100% of cases
Relative recruitment: Selected FDRs in families with 3 cases of CRC and all living FDRs in families with 3 cases of CRC
Case-3 criteria: Diagnosed in AZ (ASCR), CO (CSCR) MN (MSCC), or NH (NHCR) between 2002-2006 with incident CRC at 21-50 years of age.
Selection criteria: 100% cases
Relative recruitment: All FDRs were recruited.
Control recruitment: Controls were not recruited
FHCRC
Puget Sound SEER / Case criteria: Diagnosed in Washington’s King, Snohomish, or PierceCounties 1998-2002 with incident CRC at 20-74 years of age.
Selection criteria: 100% cases (no family history eligibility criteria).
Relative recruitment: All CRC-affected FDRs, and all living FDRs (affected and unaffected) in families with 3 or more cases of CRC, and all unaffected FDRs in approximately 50% of families with 3 cases of CRC were recruited.
Control recruitment: Non-CRC-affected individuals ascertained through the Washington State Department of Licensing were recruited as population-based controls. / Case criteria: Diagnosed in one of the 13 Western Washington SEER counties (containing 73% of the state’s population) 2002-2007 with incident CRC at 18-49 years of age.
Selection-1 criteria: 100% cases (no family history eligibility criteria).
Relative recruitment: All living FDRs were recruited.
Control recruitment: Non-CRC-affected individuals ascertained through the Washington State Department of Licensing were recruited as population-based controls.
Australasia
Victorian Cancer Registry / Case criteria: Diagnosed in Melbourne between 1997-2001 with 1st primary adenocarcinoma of colon/rectum at 18-59 years of age.
Selection-1 criteria: 100% of cases dx between the ages of 18 and 44.
Relative recruitment: All first- and second-degree relatives of the case, and all FDRs of additional CRC-affected family members.
Selection-2 criteria: 50% of cases diagnosed at 45-59 years of age (no family history eligibility criteria)
Relative recruitment: All first- and second-degree relatives of the case, and all FDRs of additional CRC-affected family members.
Control recruitment: Population-based controls federal electoral roll between the ages of 18 and 59. / Case criteria: Diagnosed in Melbourne between 2001-2006 with 1st primary adenocarcinoma of colon/rectum at 18-49 years of age.
Selection criteria: 100% of cases (no family history eligibility criteria)
Relative recruitment: All first- and second-degree relatives of the case, and all FDRs of additional CRC-affected family members.
Control recruitment: Controls were not recruited.
Cancer Care Ontario
Ontario Cancer Registry / Case criteria: Diagnosed in Ontario between 1997-2000 with incident CRC at 20-74 years of age (from 7/1/97 to 3/13/99) at 20-69 (after 3/15/99). CRC cases with a previous CRC dx and a new CRC dx in the recruitment period were considered “incident” cases and recruited
Selection-1 criteria: 100% of cases in Amsterdam-II and intermediate-risk families
Relative recruitment: 100% FDR, half-siblings on the at-risk side, and blood relatives with an HNPCC3 cancer on the at-risk side.
Selection-2 criteria: 100% cases in multiple-case families (proband with ≥ 2 FDRs or SDR <36 years with an HNPCC or other cancer
Relative recruitment: All FDRs, and half-siblings and blood relatives with HNPCC on at-risk side with their adult FDRs >17years.
Selection-3 criteria: 25% cases in single-case families
Relative recruitment: For 25% of these cases, all FDR, half siblings, and blood relatives with HNPCC with their adult FDR >17 years.
Control recruitment: Random digit dialing or Ministry of Finance file: 2000, resident of Ontario.
All cases with familial adenomatous polyposis (FAP) were excluded. / Case criteria: Diagnosed in the province of Ontario between 2003-2006 with incident CRC under 50 years of age. CRC cases with previous CRC diagnosis and a new CRC diagnosis in the recruitment period as described above were considered as “incident” cases and recruited
Selection criteria: 100% cases
Relative recruitment: All FDRs, half-siblings on at risk side (if no risk side than all half siblings), all SDRs on at-risk side only (include adult FDR if HNPCC3 affected), and all other blood relative with HNPCC3 on at risk side with their living adult FDR relatives are recruited.
Control recruitment: Controls were not recruited
All cases with familial adenomatous polyposis (FAP) are excluded.
CFR Eligibility Specifications by Center
CLINIC-BASED RECRUITMENT
CFR Site
Ascertainment Source / Phase I
(1997 – 2002) / Phase II
(2002 - 2007)
Mayo Clinic
Mayo Clinic Rochester;
North Central Cancer Treatment Group / Case criteria: Presented to clinic between 1997-2000 with CRC at 18-74 years of age.
Selection criteria: 100% cases in multiple living-case families (case has ≥ 2 living CRC-affected family members).
Relative recruitment: All living FDR (adult children with cancer, any relative with CRC along with spouses and parents. Second-degree relatives from cancer side of family (grandparents, aunts/uncles).
Selection criteria: 100% cases diagnosed under the age of 50 (no family history eligibility criteria).
Relative recruitment: Both parents, up to 4 siblings (same sex, older), any relative w/CRC along with living spouse and parents.
Control recruitment: Case spouse 18 years of age or older. / Case criteria: Presented to clinic between 2002-2007with CRC at 18-74 years.
Selection criteria: 100% cases diagnosed between 51-74 years of age in multiple-case families (must have ≥3 CRC-affected cases, at least 2 of which are living and at least 2 are 1st degree, or a living CRC-affected sibling-pair) Relative recruitment: Both parents, grandparents & aunts/uncles from cancer side. Siblings with any cancer, up to 2 unaffected siblings, adult children with cancer, any relative with CRC.
Selection criteria: 100% cases diagnosed 50 years of age (no family history eligibility criteria)
Relative recruitment: Both parents, living siblings with cancer, 2 unaffected siblings.
Selection criteria: 100% sibling pair cases (no family history eligibility criteria)Relative recruitment: Both parents, living siblings with cancer, 2 unaffected siblings.
Control recruitment: Controls were not recruited
USC Consortium
Cleveland Clinic Colorectal Cancer Registry / Case criteria: Presented to clinic with an HNPCC or HNPCC-like history (3 CRC, or 2 CRC & 1 uterine, or 2 CRC plus polyps (1 tubular villous/ villous adenoma, or one 1-cm adenoma, or ≥3 adenomas), 1 is <50 years of age and 1 is a FDR of the other two, and are in successive generations).
Selection criteria: Proband (first member of the family to contact clinic—may or not be affected) between the age of 21-75 at presentation.
Relative recruitment: All CRC-affected family members and selected unaffected family members (to 3rd degree) were recruited.
Control recruitment:Controls were not recruited / Case criteria: Presented to clinic with an HNPCC or HNPCC-like history (3 CRC, or 2 CRC & 1 uterine, or 2 CRC, plus polyps (1 tubular villous/ villous adenoma, or one 1-cm adenoma, or ≥ 3 adenomas), 1 is <50 years of age and 1 is a FDR of the other two in successive generations).
Selection criteria: Proband (first member of the family to contact clinic—may or not be affected) between the age of 21-75 at presentation.
Relative recruitment: All CRC-affected family members and selected unaffected family members (to 3rd degree to case) were recruited.
Control recruitment: Controls were not recruited
Australasia
Clinics (Brisbane, Melbourne, Adelaide, Sydney, Perth, AucklandNew Zealand) / Case criteria: Presented to a clinic with a family history of CRC or a surrogate cancer (adenoma of colorectum, endometrial, gastric, small intestinal, urinary tract, CNS) or with a strong family history of HNPCC (probands may be unaffected with CRC).
Selection criteria:
Relative recruitment: All first- and second-degree relatives of the proband or, all first and second-degree relatives of the proband on the at risk side of family, along with additional affected relatives (with CRC or related cancers).
Control recruitment: Controls were not recruited / Case criteria: Presented with a family history of CRC or surrogate cancer.
Selection criteria: (1) Any family with a known mutation (has a pathogenic germline mutation in a MMR gene AND has ≥1 living carrier, or ≥2 living FDRs of a known carrier -or- (2) All known living carriers, their FDRs, and all other living blood relatives of known carriers reporting a previous cancer diagnosis are recruited -or- (3) Any family meeting the Amsterdam I or II criteria, and in which a CR tumour has been (a) identified as MSI-H, or absent for MMR protein -and- (b) has ≥1 living CRC-affected FDR -or-(4) All living individuals with a CRC or EC tumour that is MSI-H, or is absent for a MMR gene protein (probable carriers).
Relative recruitment: All living blood relatives of probable carriers reporting a previous cancer diagnosis and all living FDRs of probable carriers are recruited.
Control recruitment: Controls were not recruited
CFR Eligibility Specifications by Center
CLINIC-BASED RECRUITMENT (continued)
CFR Site
Ascertainment Source / Phase I
(1997 – 2002) / Phase II
(2002 - 2007)
Ontario / N/A / Case criteria: (1) Amsterdam I -or- Amsterdam II criteria families –or- (2) Proband is the first affected person presenting to the clinic and is alive at the time of Phase II recruitment
-or- his/her first degree relative (if the affected proband has died)has a MMR mutation identified in a family that does not meet Amsterdam I -or- Amsterdam II criteria-or- diagnosed >49 years of age and has fresh frozen tumour banked at biospecimen repository at Mount Sinai Hospital Toronto.
Selection criteria: Recruit 100%
Relative recruitment: All FDR and half-siblings on the at risk side (if no risk side than all half siblings), all SDRs on the at-risk side only (include adult FDR if HNPCC affected), and other blood relatives with HNPCC on the at risk side with their adult FDR-only living relatives >17years.
Control recruitment: Controls were not recruited
All cases with familial adenomatous polyposis (FAP) were excluded.
CFR Eligibility Specifications by Center
PHASE III HIGH-RISK CLINIC-BASED RECRUITMENT (2007-2012)
CFR Site
Ascertainment Source / INCLUDE FAMILY EXPANSION DESCRIPTION
University of Hawaii
Ascertainment Source / Hawaii was not funded to recruit subjects in Phase III and is not expanding any existing families.
Mayo Clinic
Mayo Clinic Rochester / Recruitment criteria-1: Presenting to clinic meeting Amsterdam II criteria without the age requirement with addition of sebaceous carcinomas: Proband with colorectal cancer -and- there are 2 or more relatives with an “HNPPC associated” tumor (colorectal carcinoma, endometrial carcinoma, small-bowel carcinoma or ureter or renal pelvis carcinoma, sebaceous carcinoma) -and- one of the three is a first degree relative of the other two -and- the three cancers involve at least two generations. There are no age requirements -and- the family does not have Familial Adenomatous Polyposis (FAP)
Recruitment criteria-2: Proband with colorectal cancer and known deleterious gene mutations--(1) biallelic (2 mutations in MYH gene) -or- deleterious mutation identified in MLH1,MSH2,MSH6 or PMS2 genes.
Selection criteria:
Relative recruitment:
FHCRC
Ascertainment Source / Recruitment criteria-1: Presenting to clinic as having themselves, or being part of a family with, one or more of the following characteristics:A known, documented deleterious MMR mutation in MLH1, MSH2, MSH6, PMS2 genes -or- a known documented MutYH mutation -or- being part of a family designated as Familial Colorectal Cancer Type X -or- having a VUS mutation.
Relative recruitment: Up to 2nd degree relatives
USC Consortium
Ascertainment Source / Recruitment criteria: Present to clinic meeting MMR deleterious mutation carrier -or- MMR VUS carrier -or- Familial CRC Type X -or- Other High Risk (Phase I and II inclusion criteria)
Selection criteria: Selected participants included those living and affected with CRC or HNPCC associated cancer having MMR mutation.
Relative recruitment: 1st degree unaffected relatives between ages of 18 and 75 years of age.
- Family expansion criteria: Phase I families with research MMR gene mutation carrier, including:living 1st degree relative of MMR positive participant, individual not previously consented to CFR and >18 years of age
Australia
Ascertainment Source / New recruitment criteria: Families meeting any of the following criteria: Deleterious Variant of unknown significance (VUS) mutation in MLH1, MSH2, MSH6 or PMS2 genes, MUTYH biallelic mutation, or meeting Type X criteria (Amsterdam 1: at least 3 relatives with CRC, one of who is less than 50 years and one is a first degree relative of other 2 AND with no MMR deficiency as determined by either gene mutation analysis or MMR defect in tumor (normal IHC and/or not MSI-high). Probands may or may not be affected with CRC or any other cancer.
Relative recruitment: All FDR, half siblings of probands or relatives with a revised Bethesda criteria associated cancer and meeting colorectal polyp criteria (any polyp with villous component/ in situ or severe dysplasia/ at least 1 cm in size or with at least 3 adenomatous polypi), first degree relatives of cancer or polyp in Eligible relatives must have completed a risk factor questionnaire, provided a blood sample and given consent for access to tumor material. All first degree relatives of cancer or polyp in (2) or if an unaffected relative has a first degree relative affected with CRC, then the affected relative and all his/her first degree relatives.
Ontario
Ascertainment Source / New Family Recruitment: (British Columbia Cancer Agency (BCCA), Medical Genetics Clinic (MGC), Edmonton, Alberta, Newfoundland Colorectal Cancer Registry (NFCCR) and Familial Gastrointestinal Cancer Registry (FGICR):Families presenting at one of the preceding clinics and meeting any of the following criteria were recruited: deleterious or variant of unknown significance (VUS) mutation in MLH1 or MSH2 or MSH6 or PMS2 genes, or a MUTYH biallelic mutation, -or- meeting Type X criteria (Amsterdam 1: at least 3 relatives with CRC, one of who is less than 50 years and one is a first degree relative of other 2 AND with IHC intact tumour AND are not in all of the above 3 categories). Probands may or may not be affected with CRC or any other cancer.
Relative recruitmentThe kin selection below meeting the following criteria were eligible for recruitment: living and over the age of 18 were eligible for recruitment, which required completion of a risk factor questionnaire and/or donation of blood/saliva and/or confirm cancer diagnosis and/or access archived tumour blocks. If a cancer affected relative was deceased, they were eligible for confirmation of cancer/tumour blocks through proxy consent.
- All FDR, half siblings of probands or relatives with a revised Bethesda criteria associated cancer and meeting colorectal polyp criteria (any polyp with villous component/ in situ or severe dysplasia/ at least 1 cm in size or with at least 3 adenomatous polypi), first degree relatives of cancer or polyp in Eligible relatives must have completed a risk factor questionnaire, provided a blood sample and given consent for access to tumor material. All first degree relatives of cancer or polyp in (2) or if an unaffected relative has a first degree relative affected with CRC, then the affected relative and all his/her first degree relatives.
All sites but Hawaii / Family Expansion Criteria:
Family criteria: Existing phase I and II families (population or clinic based ) meeting any of the above criteria (MLH1/MSH2/MSH6/PMS2 deleterious or VUS mutation or MUTYH biallelic mutation or type X) were selected for expansion.
Relative recruitment: Any relative who was alive and at least 18 years old AND meeting above expansion criteria (1-5) who was not yet recruited was eligible for recruitment through expansion activity (completing risk factor questionnaire, and /or donating blood/saliva and /or confirmation of cancer diagnosis). Only CRC blocks were collected for molecular characterization (IHC). Confirmation of cancer diagnosis and/or tumour block was sought even if the affected individual was deceased.
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