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.
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ABSTRACT: Determine whether colorectal cancer (CRC) rates are disproportionately high in the French-Acadian region (population 1.2 million) of Louisiana, home of the Cajuns, a founder population.Clinical and translational gastroenterology. 10/2014; 5:e60.
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ABSTRACT: Including low penetrance genomic variants in population-based screening might enable personalization of screening intensity and follow up. The application of genomics in this way requires formal evaluation. Even if clinically beneficial, uptake would still depend on the attitudes of target populations. We developed a deliberative workshop on two hypothetical applications (in colorectal cancer and newborn screening) in which we applied stepped, neutrally-framed, information sets. Data were collected using nonparticipant observation, free-text comments by individual participants, and a structured survey. Qualitative data were transcribed and analyzed using thematic content analysis. Eight workshops were conducted with 170 individuals (120 colorectal cancer screening and 50 newborn screening for type 1 diabetes). The use of information sets promoted informed deliberation. In both contexts, attitudes appeared to be heavily informed by assessments of the likely validity of the test results and its personal and health care utility. Perceived benefits included the potential for early intervention, prevention, and closer monitoring while concerns related to costs, education needs regarding the probabilistic nature of risk, the potential for worry, and control of access to personal genomic information. Differences between the colorectal cancer and newborn screening groups appeared to reflect different assessments of potential personal utility, particularly regarding prevention.Genome 10/2013; 56(10):626-33. · 1.56 Impact Factor
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ABSTRACT: Colorectal cancer is a common malignancy. Identification of genetic prognostic markers may help prognostic estimations in colorectal cancer. Genes that regulate response to hypoxia and other genes that are regulated under the hypoxic conditions have been shown to play roles in cancer progression. In this study, we hypothesized that genetic variations in the hypoxia pathway genes were associated with the risk of outcome in colorectal cancer patients. This study was performed in two phases. In the first phase, 49 SNPs from six hypoxia pathway genes (HIF1A, HIF1B, HIF2A, LOX, MIF and CXCL12) in 272 colorectal cancer patients were analyzed. In the second phase, 77 SNPs from seven hypoxia pathway genes (HIF1A, HIF1B, HIF2A, HIF2B, HIF3A, LOX and CXCL12) were analyzed in an additional cohort of 535 patients. Kaplan Meier, Cox univariate and multivariable regression analyses were performed to analyze the relationship between the SNPs and overall survival (OS), disease free survival (DFS) or disease specific survival (DSS). Since this was a hypothesis-generating study, no correction for multiple testing was applied. In phase I, one SNP (HIF2A rs11125070) was found to be associated with DFS in multivariable analysis; yet association of a proxy polymorphism (HIF2A rs4953342) was not detected in the phase II patient cohort. In phase II, associations of two SNPs (HIF2A rs4953352 and HIF2B rs12593988) were significant in both OS and DFS multivariable analyses. However, association of HIF2A rs4953352 was not replicated in the phase I cohort using a proxy SNP (HIF2A rs6706003). Overall, our study did not find a convincing evidence of association of the investigated polymorphisms with the disease outcomes in colorectal cancer.PLoS ONE 11/2014; 9(11):e113513. · 3.53 Impact Factor