Very high incidence of familial colorectal cancer in Newfoundland: a comparison with Ontario and 13 other population-based studies

Abstract

Newfoundland has the highest rate of colorectal cancer (CRC) of any Canadian province. In order to investigate the factors, especially genetic components, responsible for CRC we established the Newfoundland Colorectal Cancer Registry. In a 5-year period we examined every case of CRC diagnosed under the age of 75 years and obtained consent from 730 cases. Careful analysis of family history was used to assign a familial cancer risk, based on established criteria. We observed that 3.7% of CRC cases came from families meeting the Amsterdam II criteria and a further 0.9% of cases involved familial adenomatous polyposis (FAP). An additional 43% of cases met one or more of the revised Bethesda criteria and 31% of all cases had a first-degree relative affected with CRC. We compared the Newfoundland data with data from the province of Ontario, where the same recruitment and risk-assessment criteria were used. In all categories, the indicators of familial risk were significantly higher in Newfoundland. These data were also compared to results published from 13 other population-based studies worldwide. In every category the proportion of Newfoundland cases meeting the criteria was higher than in any other population. The mean differences were: 3.5-fold greater for FAP, 2.8-fold higher for Amsterdam criteria, 2.0-fold higher for Bethesda criteria and 1.9-fold higher for the number of affected first-degree relatives. We conclude that the high incidence of CRC in Newfoundland may be attributable to genetic, or at least familial, factors. In the high-risk families we provide evidence for the involvement of founder mutations in the APC and MSH2 genes.

Evaluation of a population‐based approach to familial colorectal cancer

“…This compares with 61% of incident cases who provided family histories to the NFCCR, a prior research project that required research consent 2. However these proportions contrast with the observation that in Australia only 1% of unaffected people at potentially high risk of CRC reported appropriate screening 24.…”

“…In all categories used to define family risk of CRC, the incidence was significantly higher in NL compared to Ontario, and NL had the highest rate of familial CRC worldwide when compared to other population‐based studies 2.…”

“…OFCCR included 20% of low familial risk cases whereas NFCCR included all low risk cases. Participant recruitment and details regarding data collection have been previously described 2, 30. Once consent was obtained, individuals provided demographic information, family history for CRC, and epidemiological data, and also consented to providing a DNA sample and access to tissue blocks.…”

Public attitudes towards genomic risk profiling as a component of routine population screening

“…Ottawa is a large, mostly urban population with CRC incidence reflecting the Canadian average and overall relatively high socio-economic status, whereas St John's is a smaller urban population with a high incidence of CRC (Green et al 2007;Woods et al 2005) and a broader socio-economic mix. Additionally, ON and NL have different newborn screening programs in terms of both organization and number of conditions included.…”

Cytochrome P450 17A1 and Catechol O-Methyltransferase Polymorphisms and Age at Lynch Syndrome Colon Cancer Onset in Newfoundland

“…The incidence and mortality rates for colorectal cancer in the Canadian province of Newfoundland and Labrador rank among the highest in the world (1), partly explained by a high prevalence of familial cancer (2). Lynch syndrome is an autosomal dominant genetic syndrome characterized by early age at colon cancer diagnosis and the common occurrence of tumors in the gastrointestinal, upper urologic, and female reproductive tracts (3).…”