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.

Atlantic Breast Cancer Information Project: formation of a "town-gown" partnership.

The Atlantic Breast Cancer Information Project (ABCIP) is one of 5 breast cancer information exchange projects funded by Health Canada. This article describes the development of ABCIP and thereby contributes to the limited knowledge on successful partnership formation in the face of restraints but with support from enabling factors. Partnership formation is presented in the context of alliances in management, coalitions in health promotion, and social movements. The restraining factors were the inertia of the status quo, provincial structures and concerns about empowering others. The enabling factors fell into 3 categories: timely logistics, roles of individuals who participated at critical points in the process, and the evolution of a supportive cultural environment. The article outlines ABCIP's achievements to date.

Effectiveness of a call/recall system in improving compliance with cervical cancer screening: a randomized controlled trial.

OBJECTIVE: To determine the effectiveness of a simple call/recall system in improving compliance with cervical cancer screening among women not screened in the previous 3 years. DESIGN: Prospective randomized controlled study. SETTING: Two family medicine clinics (1 urban, 1 rural) affiliated with Memorial University of Newfoundland, St. John's. PARTICIPANTS: A sample of women aged 18-69 years who were listed as patients of the clinics but who had not had a Papanicolaou test (Pap test) within the 3 years before the start of the study. Of 9071 women listed as patients 1360 (15.0%) had not undergone screening in the previous 3 years. A random sample of 650 were selected, 209 of whom were excluded because they had had a hysterectomy, had had a recent Pap test, had moved or had records containing clerical errors. This left 441 women for the study. INTERVENTION: The 221 women in the intervention group were sent a letter asking them to seek a Pap test and a reminder letter 4 weeks later. The 220 in the control group were sent no letters. MAIN OUTCOME MEASURES: Number of women who had a Pap test within 2 months and 6 months after the first letter was sent. RESULTS: Within 2 months, more women in the intervention group than in the control group had been screened (2.8% [5/178] and 1.9% (4/208] respectively). There was also a difference between the overall proportions at 6 months (10.7% [19/178] and 6.3% [13/208] respectively). None of the differences was statistically significant. CONCLUSION: A letter of invitation is not sufficient to encourage women who have never or have infrequently undergone a Pap test to come in for cervical cancer screening. The effectiveness of added recruitment methods such as opportunistic screening by physicians, follow-up by telephone and the offer of a specific appointment should be evaluated.

Lung cancer in Newfoundland, Canada.

In this study 1,466 cases of primary lung cancer diagnosed between 1974 and 1983 and reported to the Provincial Tumour Registry, were reviewed. The incidence of lung cancer in Newfoundland has been lower than that in Canada as a whole. The age-adjusted rates for Canadian males and females were 56 and 14 per 100,000 compared to 45 and 7 in Newfoundland. Census division rates showed no association with socioeconomic indicators. The rate in one census division was higher (63 vs 53) most probably because of the higher risk of men who worked in the St. Lawrence fluorspar mines. Although Newfoundland's current smoking rates (39% of men over 15 and 29% of women over 15) are high, this is not reflected in lung cancer rates. Smoking was not widely accepted in rural areas until the time of World War II, and Newfoundland's lower rates may be due to this delay in exposure.

Tuberculosis associated with HLA--B8, BfS in a Newfoundland community study.

In three adjacent Newfoundland communities comprising some 1500 people, 589 people have been HLA typed. Forty-six of the typed people gave a history of previous clinical tuberculosis which required treatment. Fifty-six percent of the TB patients carried HLA B8 compared with 20% of the remainder of the population. This is a highly significant difference (P less than 0.01). In each community the frequency of B8 as an epidemiological marker correlated with the incidence of tuberculosis. B8 is associated with TB in ths study with a relative risk of 5.2 which compares with combined relative risks in the literature for coeliac disease and Addison's disease of 9.5 and 6.4, respectively, and which is greater than the risks for all the other B8-related diseases. The factor B allele, Bf S, was found on all the B8 haplotypes, but the overall Bf gene frequencies in tuberculosis patients did not deviate from expected values.

Bf types of HLA haplotyped individuals in an isolated Newfoundland population.

Five hundred and fourteen individuals from an isolated NewFoundland population have been typed and haplotyped for HLA and Factor B (Bf locus). The Bf gene frequencies were: S0.704, F0.226, F1 0.052 and S1 0.018. Tracing the haplotypes backwards on the various pedigrees it was shown that 202 HLA/Bf haplotypes had been introduced into the study population. Some HLA alleles always appeared in association with particular Bf alleles and vice versa. Bf S1 had entered the population four times, always with HLA--A9, B12. Bf F1 had entered three times, always with HLA--B18. There were 17 entries of HLA--Al, B8 that had given rise to the 78 such haplotypes that were now present in the population; all were Bf S. There were 68 family units informative for Bf. They accounted for 240 children and 304 informative meioses. There were three recombinants in the HLA region but none could be shown to have occurred between the HLA-B and Bf loci.

HLA in familial Hodgkin's disease. Results and a new hypothesis;.

A familial aggregate of seven cases of Hodgkin's disease (HD) has been investigated by HLA typing. Over 600 people in the immediate population (i.e. about half) have been HLA typed and haplotypes have been obtained for 95% of them. It was expected that the cases would share a particular HLA haplotype or at least that they would have one or two HLA antigens of the same series in common. However, this was not the case so no simple idea of association of HLA with HD cases was upheld. When antigen frequencies were examined in the whole population, it was found that HLA B18 increased progressively in incidence from 0.08 to 0.4 in successive groups of individuals each one more closely related to the HD cases. Similarly the community with the highest incidence of HD also had the highest incidence of B18. Thus B18, which in the world figures carries the highest relative risk, emerged as important in this study. Of four proposed interpretations of the data, we are most interested in the idea that the important HLA association is at a population level rather than at the level of the individual patient. A hypothesis, based on the concept of a "healthy carrier" for the HD agent, explains how such an association might operate. It is possible that B18-linked complement deficiency could be the basis for such a carrier state.

HLA haplotypes in a genetic isolate in Newfoundland. A population showing 8% homozygosity and a familial aggregate of lymphoma and immunodeficiency cases.

HLA typing was performed on 384 individuals of an isolated population of 1,500 people with a familial aggregate of lymphoma and immunodeficiency cases. Eighty-five % of the total population were descendants of the founding couple. First cousin marriages were common. There was a three-fold or higher increase of the following haplotypes as compared to the frequencies in Sheffield: HLA-A28,Bw35, HLA-A28, B18, HLA-A10, B18, HLA-A2, B18,HLA-A11, Bw40 and HLA-A11, B7. The frequency of HLA-A1, B8 was low (5.4%). The most common genotype was HLA-A2, B12/A2, B12 followed by HLA-A2, B12/A28, Bw35. We found 20 HLA homozygous individuals, of these 15 were HLA-A2, b12/a2, b12. There were two possible HLA cross-overs which may be confirmed and three postulated cross-overs which can never be confirmed as one or both parents of the individuals in question are deceased. Some of the haplotypes could be traced back to the first, second and third generations, i.e. to the first half of the nineteenth century. No single haplotype or antigen was shared by the patients.

An immunoglobulin in Newfoundland with the genetic marker Glm/z) without Glm(a) in five siblings: a possible hybrid molecule.

Inheritance of Glm(z) without Glm(a) was found in five members of a Newfoundland family. The investigations were suggestive for the transmission of a Gm haplotype (z;n-;g) coding for Glm(z) and nGlm(a) at the Fd and Fc parts, respectively, of the IgGl heavy chain.

A comparison of the direct and indirect leukocyte migration tests in man.

In the Direct Leukocyte Migration Test, as few as 10% mononuclear cells are sufficient to produce antigen-specific inhibition of polymorphonuclear leukocyte migration in the presence of 100 mug of excipient-free PPD per ml. A clear distinction between tuberculin-positive and tuberculin-negative donors can be made. The inhibition of migration is blocked by the presence of actinomycin D. In the Indirect Test, significant inhibition of migration of pure polymorphs is produced by supernatants from stimulated tuberculin-sensitive lymphocyte cultures. Inhibition is maximal at 6 h and is of a similar degree to that obtained in the direct test.

Inflammatory factors produced by sensitized guinea-pig peripheral blood lymphocytes.

The supernatants obtained from stimulated tuberculin-sensitive guinea-pig peripheral blood lymphocytes contain factors that induce a cutaneous inflammatory response in normal guinea-pigs similar to the tuberculin reaction and inhibit the migration of normal guinea-pigs peritoneal exudate cells. There appears to be a correlation between the presence of in vitro migration inhibitory activity and inflammatory activity in vivo.

Inflammation-inducing factors from human lymphocytes. Correlation with polymorphonuclear leucocyte migration enhancement of inhibition.

Factors capable of inducing inflammatory reactions in the skin of normal guinea pigs have been demonstrated in culture supernatants from PPD-stimulated human mononuclear cells from tuberculin-positive donors. The reaction is characterised by erythema, induration and infiltration with mononuclear cells and some polymorphonuclear leucocytes. These supernatants either enhance or do not affect polymorph migration in the leucocyte migration test. Supernatants that inhibit migration in vitro produce a marked polymorph infiltration upon intradermal injection.

Common variable immunodeficiency, Hodgkin's disease, and other malignancies in a Newfoundland family.

A large inbred family is described in which there were seven cases of Hodgkin's disease, three of lymphosarcoma, two of thymoma, two of common variable immunodeficiency, and single cases of retinoblastoma, neuroblastoma, and rhabdomyosarcoma. There have been no other lymphoma cases in the community during the past decade. Further study of this family may help to define the genetic basis for development of Hodgkin's disease and other disorders.