Participants in this study were recruited by the Australasian Colorectal Cancer Family Registry (ACCFR), a large family cohort which is part of the Colon Cancer Family Registry, an international consortium funded by the National Cancer Institute (U.S.A.) (Newcomb et al. 2007 ). The ACCFR was established in 1997 and currently contains data from approximately 10,500 participants representing approximately 1500 colorectal cancer families. The ACCFR recruited family members via population-based probands (i.e., recently diagnosed CRC cases) from the Victorian Cancer Registry (Australia), and via clinic-based probands from multiple-case families referred to family cancer genetics clinics in Australia (Melbourne, Adelaide, Perth, Brisbane, Sydney) and New Zealand (Auckland).
At the time of recruitment for this study there were 1250 ACCFR participants from 188 mismatch repair gene mutation-carrying families. Deceased participants and those lost to followup were excluded. To be eligible for this study, participants had to be from families in which at least one person had been identified by genetic testing as carrying a deleterious mutation in a mismatch repair gene, had to be between 18 and 69 years old at recruitment into this study, had no previous diagnosis of CRC or any other cancer, and had to have declined an offer within the previous ten years by the ACCFR to attend a genetics service to receive their individual genetic test results (n = 134). Of these, 47 agreed to be contacted about the study; 21 of these were found to be ineligible because of having previous genetic testing or cancer, or they subsequently declined to be interviewed. The 26 participants included in the study represent 22 mismatch repair mutation-carrying families (two participants per family for four families). Screening for germline mutations in MLH1, MSH2, MSH6 and PMS2 was performed for all population-based probands who had a colorectal tumour displaying evidence of impaired mismatch repair function. Impaired mismatch repair was evidenced by either microsatellite instability (MSI), or by lack of mismatch repair protein expression by immunohistochemistry. Screening was performed also for the youngest onset CRC case from each clinic-based family regardless of MSI or mismatch repair protein expression status, and for their family members if they were found to have deleterious mismatch repair gene mutations (described in detail elsewhere) (Win et al. 2012 (link)). Participant characteristics including mutation status are summarised inTable 1 .
This study was approved by the Human Research Ethics Committee of the University of Melbourne and all participants gave informed consent.
At the time of recruitment for this study there were 1250 ACCFR participants from 188 mismatch repair gene mutation-carrying families. Deceased participants and those lost to followup were excluded. To be eligible for this study, participants had to be from families in which at least one person had been identified by genetic testing as carrying a deleterious mutation in a mismatch repair gene, had to be between 18 and 69 years old at recruitment into this study, had no previous diagnosis of CRC or any other cancer, and had to have declined an offer within the previous ten years by the ACCFR to attend a genetics service to receive their individual genetic test results (n = 134). Of these, 47 agreed to be contacted about the study; 21 of these were found to be ineligible because of having previous genetic testing or cancer, or they subsequently declined to be interviewed. The 26 participants included in the study represent 22 mismatch repair mutation-carrying families (two participants per family for four families). Screening for germline mutations in MLH1, MSH2, MSH6 and PMS2 was performed for all population-based probands who had a colorectal tumour displaying evidence of impaired mismatch repair function. Impaired mismatch repair was evidenced by either microsatellite instability (MSI), or by lack of mismatch repair protein expression by immunohistochemistry. Screening was performed also for the youngest onset CRC case from each clinic-based family regardless of MSI or mismatch repair protein expression status, and for their family members if they were found to have deleterious mismatch repair gene mutations (described in detail elsewhere) (Win et al. 2012 (link)). Participant characteristics including mutation status are summarised in
This study was approved by the Human Research Ethics Committee of the University of Melbourne and all participants gave informed consent.
