Hereditary nonpolyposis colon cancer: analysis of linkage to 2p15-16 places the COCA1 locus telomeric to D2S123 and reveals genetic heterogeneity in seven Canadian families.

Hereditary nonpolyposis colon cancer (HNPCC) is an autosomal dominant trait responsible for approximately 6% of colorectal cancers. Linkage of the HNPCC trait to the D2S123 locus on 2p15-16 has previously been reported in two families. This HNPCC locus is now designated "COCA1." We have tested seven Canadian HNPCC families, who have a variety of clinical presentations, for linkage to a panel of microsatellite polymorphisms in the vicinity of D2S123. One family was clearly linked to the COCA1 locus (LOD = 4.21), and a second family is likely to be linked (LOD = 0.92). In three families linkage was excluded. In the remaining two families the data were inconclusive. In the linked family, individuals with cancer of the endometrium or ureter share a common haplotype with 12 family members with colorectal cancer. This supports the suspected association between these extracolonic neoplasms and the HNPCC syndrome. In addition, five of the six individuals with adenomatous polyps (but no colorectal cancer) have the same haplotype as the affected individuals, while the sixth carries a recombination. One individual with colorectal cancer carries a recombination that places the COCA1 locus telomeric to D2S123. This study localizes the COCA1 gene to an 8-cM region that is consistent with the location of the hMSH2 gene. We also confirm that families presently classified as HNPCC are genetically heterogeneous.

Hereditary site-specific colon cancer in a Canadian kindred.

In summary, we have presented a large Canadian kindred exhibiting hereditary large bowel cancer, without polyposis coli, transmitted in an autosomal dominant fashion (Hereditary Site-Specific Colon Cancer). This series serves to emphasize the heritable nature of this and other malignant conditions and the importance of so fundamental a concept as the taking of a complete family history in the identification and management of these conditions. Looking to the future, the reduction of morbidity and mortality from Hereditary Site-Specific Colon Cancer lies in the education of the family and genetic counselling, both commencing in the mid teens the education of physicians and surgeons in the very considerable risk of malignancy in this condition the surveillance of asymptomatic family members including such measures as stool testing for occult blood six monthly augmented by air contrast barium enema and/or colonoscopy at two yearly intervals, commencing at age 25 the creation of national and international registries the identification of reliable biomarkers. We are indeed fortunate to live in a age when technology holds promise for the identification of the oncogenes operative in this and other heritable malignancies. This is the subject of ongoing collaboration between us and our molecular biology colleagues at Memorial University in St. John's and exemplifies, I believe, the very best in the cooperative spirit which may exist between a community hospital and a larger teaching centre.

Pancreatitis in northern Newfoundland and Labrador: a 20-year review of the Grenfell Regional Health Services experience.

A retrospective review of the Grenfell Regional Health Services experience with pancreatitis over a 20-year period (1968-1987) has been presented. The small number of cases in this series precludes meaningful statistical analysis, however, in general, one can state that native peoples are represented in this study in roughly the same proportion as they are represented in the population served. We have demonstrated that pancreatitis in its chronic form does occur in the Inuit of Northern Labrador. Given the prominent role that alcohol abuse plays in the social and behavioral ills of Labrador's native peoples as reflected in the high incidence of family violence, accidental deaths, and suicides, one might anticipate a disproportionately high incidence of pancreatitis and its chronic sequelae among the Inuit. The answer to this seeming paradox may be found through future study of the nature of the alcohol consumed, its pattern of consumption or of genetically-determined differences in the metabolism of alcohol and its toxic effects within the body, of differences in the composition of pancreatic secretions, or of environmental and dietary factors.

Gastric torsion.

We report a seven-week-old baby girl with a one-day history of vomiting and respiratory distress. The radiological findings were those of intrathoracic mesenteroaxial torsion of the stomach complicating a large hiatus hernia which included part of the small bowel and colon with partial colonic obstruction. This is a rare but important cause of alimentary tract obstruction and respiratory distress in infants. Prompt diagnosis and correction are vital.

Hereditary site-specific colon cancer in a Canadian kindred.

A large kindred with colorectal cancer unaccompanied by polyposis coli and characterized by autosomal dominant inheritance has been identified in eastern Canada. Ten family members from three successive generations have presented 17 documented colorectal cancers. The clinical features of the kindred are characteristic of hereditary site-specific colon cancer (HSSCC) (Lynch syndrome I): absence of multiple polyposis, autosomal dominant inheritance, onset of colorectal cancer at an early age and a high incidence of synchronous and metachronous colorectal cancers. A unique feature of this family is the high incidence of sporadic adenomatous polyps in affected members and their relatives. Patients with HSSCC have been managed by means of segmental colectomy followed by annual colonoscopic surveillance. All five patients with localized (Dukes' stage A or B) cancer at initial diagnosis were alive and free of disease after 2 to 12 years of follow-up, although three had required further colonic resection for metachronous carcinomas. Five young family members without cancer have had sporadic adenomatous polyps removed and are being followed with annual colonoscopy. It is not known whether polypectomy will alter the subsequent incidence of colon cancer. Subtotal colectomy is recommended for patients with HSSCC because of the high incidence of multiple lesions. An aggressive screening protocol, including colonoscopy, is recommended for all adult first- and second-degree relatives of patients with HSSCC. Identification of a biomarker, which is currently being sought in this kindred, would help identify those at greatest risk of development of cancer and allow earlier intervention.

Snowmobile injuries in northern Newfoundland and Labrador: an 18-year review.

The charts of 310 consecutive patients with snowmobile injuries admitted to Charles S. Curtis Memorial Hospital, St. Anthony, Newfoundland, during the years 1969 through 1986 were reviewed in order to determine the causes and possible ways of prevention of these injuries. There were 237 males and 73 females. Most patients were less than 30 years of age (73%). Drivers represented 57% of the injured. Falling off the machine and collisions were responsible for 60% of the injuries; 3.0% were due to mechanical failure of the snowmobile. The lower limbs and head and neck regions were most commonly affected (42.6 and 27.6%, respectively); less than 10% of the patients were wearing helmets at the time of the accident. We conclude that the human factor was responsible for the majority of the injuries. We recommend enforcement of legislation, intensification of public education about the hazards of driving snowmobiles, and modifications in the design of the engine, especially to provide increased protection for the lower limbs.