Very high incidence of familial colorectal cancer in Newfoundland: a comparison with Ontario and 13 other population-based studies.
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.
Green
R C
RC
Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada. rcgreen@mun.ca
Green
J S
JS
Buehler
S K
SK
Robb
J D
JD
Daftary
D
D
Gallinger
S
S
McLaughlin
J R
JR
Parfrey
P S
PS
Younghusband
H B
HB
D011125:Adenomatous Polyposis Coli / Q000453:epidemiology / Q000235:genetics; D017668:Age of Onset; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000601:surgery; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology / Q000235:genetics; D005191:Family Characteristics; D005260:Female; D017491:Genes, APC / Q000502:physiology; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D015994:Incidence; D008297:Male; D051718:MutS Homolog 2 Protein / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000235:genetics*; D009523:Newfoundland and Labrador / Q000453:epidemiology; D009864:Ontario / Q000453:epidemiology; D010375:Pedigree; D011159:Population Surveillance; D011230:Precancerous Conditions / Q000175:diagnosis / Q000453:epidemiology / Q000601:surgery; D012042:Registries; D018570:Risk Assessment / Q000706:statistics & numerical data
D051718:MutS Homolog 2 Protein