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D T Bishop

Publications and source records attributed to D T Bishop.

At least 109 records · Page 6Linked to original sources
PubMed1994

Family studies in melanoma: identification of the atypical mole syndrome (AMS) phenotype.

Thirteen families have been studied clinically as the basis for a linkage study of susceptibility to cutaneous melanoma. Previous studies have shown that a number of families with predisposition to melanoma have abnormal naevi, now known as the atypical mole syndrome (AMS) phenotype. Many groups performing linkage studies using families selected from geographical areas with higher rates of melanoma have concentrated on the diagnosis of melanoma to identify presumptive gene carriers. In the UK, in the absence of extended families with multiple cases of melanoma, we have attempted to identify gene carriers through the presence of the AMS phenotype. Previously the AMS phenotype has been poorly defined and so we have developed a scoring system to define the AMS in an attempt to allow for variation in expression among gene carriers. In this report, we document the clinical characteristics of all 13 families and the use of our scoring system. The pattern of inheritance within these selected families of the AMS phenotype with or without melanoma is consistent with a dominant gene.

Analysis of Variance↗
PubMed1994

Genetic heterogeneity of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in families with familial adenomatous polyposis.

One hundred and eighteen subjects with familial adenomatous polyposis (FAP) and 80 of their relatives who were at low risk (< 0.01) of carrying the FAP gene were scored by one of us (BJ) or by colleagues to assess the frequency of congenital hypertrophy of the retinal pigment epithelium (CHRPE). A CHRPE is defined as an "oval pigmented lesion surrounded by depigmented halo". Seventy five (63.6%) of the FAP cases and one (1.2%) of their relatives had at least one CHRPE. There was no systematic difference in the number of CHRPEs in the left and right eyes so all analyses are based on total number of CHRPEs and the findings were highly correlated (p = 0.001 for a test of no correlation). There was also no evidence of any age effect in total number of CHRPEs in affected subjects. In 26 families there was more than one subject affected with FAP. There was a significant common family effect with respect to CHRPE expression for total number of CHRPEs with an F statistic of 1.73 (p = 0.02 for a test of no family aggregation) indicating that family members are more similar to each other than to affected subjects from other families. This may indicate that specific mutations play a role in determining the number of CHRPEs. Nine affected subjects had intra-abdominal desmoids, and in these the frequency of each of the types of CHRPE was no higher (in fact, slightly lower) than the average for affected subjects without desmoids, but this difference was not significant (p > 0.3).

Adenomatous Polyposis Coli↗
PubMed1994

Muir-Torre syndrome: a variant of the cancer family syndrome.

Muir-Torre syndrome is characterised by the association of sebaceous tumours of the skin with internal malignancy. In many instances there is a strong family history of cancer and the autosomal dominant mode of inheritance, tumour spectrum, and high incidence of synchronous and metachronous tumours show parallels with the cancer family syndrome or Lynch II syndrome. We report a five generation family with at least two persons displaying the Muir-Torre phenotype, while many other family members have had tumours consistent with cancer family syndrome. The majority of tumours are gastrointestinal, gynaecological, and urological, with several persons having multiple primaries. The prognosis appears to be better than would be expected. Sebaceous tumours are a marker for internal malignancy and should prompt a search for occult cancer in the individual person and family members. In documented Muir-Torre families, at risk persons should be entered into screening programmes similar to those used in the Lynch II syndrome.

Adult↗
PubMed1994

Colonic polyps in an unselected population: prevalence, characteristics, and associations.

OBJECTIVES: To provide a proctosigmoidoscopic review of a very large set of unselected control subjects, providing an unbiased view of colonic polyps in the general population. METHODS: Sigmoidoscopic data from 406 sequentially recruited subjects were analyzed. Participation rates were over 85%, and subjects were thus free of the usual selection bias. RESULTS: Thirty-eight percent of screened individuals were found to have distal colonic polyps. Adenomas were found in 12%, and hyperplastic polyps were found in 30% of screened individuals. Adenomas were more prevalent in males and in older individuals. Hyperplastic prevalence did not differ significantly by gender or age. Synchronous adenomatous and hyperplastic polyps occurred in 3% of screened individuals, but these lesions were not associated. CONCLUSIONS: Distal colonic adenomatous and hyperplastic polyps are very common in the general population and are not associated. The high frequency of these polyps raises questions about the feasibility of biopsy for all polyps, and suggests that further study is needed to determine the appropriate indications for subsequent colonoscopy.

Adenomatous Polyps↗
PubMed1993

How common is the atypical mole syndrome phenotype in apparently sporadic melanoma?

BACKGROUND: Although patients from some families with the atypical mole syndrome (AMS) are predisposed to melanoma, it is not known how frequently this underlies the apparently sporadic presentation of melanoma. OBJECTIVE: This study was designed to estimate the frequency of the AMS (dysplastic nevus or FAMMM syndrome) phenotype in a population-based study of patients with melanoma in the United Kingdom and to determine the prevalence of the phenotype in the relatives of the patients with AMS. METHODS: The nevi of patients with melanoma and controls in a case-control study, and the nevi of some relatives of patients with AMS, were examined. An AMS scoring system was used to define the AMS phenotype. The familiarity of the AMS phenotype was then determined by screening first-degree relatives of persons with the AMS phenotype. RESULTS: Forty of 266 (15%) of patients with melanoma had the AMS phenotype compared with 7 of 305 (2%) of the controls (odds ratio 7.5, 95% confidence interval 3.4-16.8). Screening of relatives of patients with melanoma who had the AMS phenotype identified the same phenotype within the families, providing evidence that the AMS phenotype in patients with melanoma is predictive of the same phenotype in relatives, consistent with so-called type D1 AMS. CONCLUSION: The AMS phenotype is a potent risk factor for cutaneous melanoma and is present in 15% of patients. Melanoma in the United Kingdom is more common in women than in men, but the AMS phenotype was more frequent in men in this study. It is our hypothesis that the effects of the putative AMS gene are diluted by environmental factors in U.K. women. Screening of relatives of patients with melanoma who have the AMS phenotype may identify persons at increased risk of melanoma.

Adolescent↗
PubMed1993

Genetic analysis of the BRCA1 region in a large breast/ovarian family: refinement of the minimal region containing BRCA1.

We have analyzed a single multi-affected breast/ovarian cancer pedigree (BOV3) and have shown consistent inheritance of markers on chromosome 17q with the disease confirming that this family is due to the BRCA1 gene. Analysis of 17q haplotypes shows a recombination event in a bilateral breast cancer case which suggests that the BRCA1 gene lies distal to D17S857; D17S857 is thus the new proximal boundary for the region containing BRCA1. Combining this information with previously published mapping information suggests that BRCA1 is contained in a region estimated at 1-1.5 Mb in length. All seven breast tumour/blood pairs examined from this family show loss of heterozygosity in the tumours. The allel retained in each tumour was from the disease-bearing chromosome implicating BRCA1 as a tumour suppressor gene. We have sequenced the 17 beta-oestradiol dehydrogenase genes (EDH17B1 and EDH17B2) which have been suggested as candidate genes for BRCA1 in four members of this family. No germline mutations were detected.

Alleles↗
PubMed1993

Feasibility of family based screening for colorectal neoplasia: experience in one general surgical practice.

Relatives of patients with colorectal cancer have on average a two to threefold increased risk for developing bowel neoplasia although in some families the risk is much higher. This study examined the compliance for endoscopic screening and faecal occult blood testing among first degree relatives of patients with colorectal cancer to determine the feasibility of offering a screening service in a surgical practice. The endoscopic method (flexible sigmoidoscopy or colonoscopy) offered depended upon the extent of family history. Spouses of patients were offered flexible sigmoidoscopy as a group for comparison. Compliance in first degree relatives was significantly higher than in spouses (69% v 47%, p < 0.01) and among those relatives of patients who had died recently from colorectal cancer but time since diagnosis in the index case had no effect. Adenomas were found in 14 of 92 (15%) relatives and three of 30 (10%) spouses. It is estimated that, under our screening guidelines, every 100 patients with colorectal cancer would generate a list of 35-40 relatives who would be screened once by flexible sigmoidoscopy and perhaps 75, who because of their young age, might be screened twice in their lifetime. Also, from this same 100 patients, about 12-15 relatives would merit entry in a colonoscopic screening programme because of their more extensive family history. These results indicate that endoscopic screening of relatives of patients with colorectal cancer is feasible within a practice.

Adult↗
PubMed1993

p53 protein detected by immunohistochemical staining is not always mutant.

The expression of the tumour suppressor gene p53 was analyzed in a variety of human solid tumours by immunohistochemistry and direct DNA sequencing. Positive nuclear staining using a panel of anti-p53 antibodies was used to select tumours for further genetic analysis. Using PCR amplification followed by immobilization onto magnetic beads and direct sequencing, we sequenced exons 5-9 of the p53 gene from 9 melanomas, 8 nasopharyngeal carcinomas, 16 sporadic breast carcinomas and 11 patients from familial breast cancer families. No sequence alterations of the p53 gene were detected in either the melanoma or nasopharyngeal tumours and only 19% of the primary breast carcinomas showed a variant band indicative of a mutation. Our results indicate firstly that p53 mutations are not generally involved in the tumour types studied and secondly the data emphasize the disparity encountered when attempting to correlate p53 immunohistochemical positivity with mutations within the p53 gene.

Breast Neoplasms↗
PubMed1993

Distribution of lod scores under uncertain mode of inheritance.

We consider probability distributions of alternative lod statistics, differing in their treatment of segregation parameters when mode of inheritance is uncertain. A particular pedigree structure and a dominant genetic system displaying incomplete penetrance are analyzed. Lod scores calculated assuming an incorrect segregation model appear to conform quite well to the chi 2 distribution in the absence of linkage. In the presence of linkage, some power is lost. However, if lod scores are calculated under several different segregation models and the best one is accepted, opportunity for chance occurrence of high lod scores is enhanced. The distribution is still chi 2, but with extra degrees of freedom. These results hold over a wide range of sample sizes and segregation models, including small samples and low levels of penetrance.

Chi-Square Distribution↗
PubMed1993

Five cases of coexistent primary ocular and cutaneous melanoma.

BACKGROUND: Patients with the atypical mole syndrome are prone to cutaneous melanoma, but their risk of ocular melanoma has not been established. We studied the skin of 207 consecutive patients with eye melanoma referred to Moorfields Hospital in London, England, in an attempt to determine what percentage of these patients had the atypical mole syndrome phenotype. OBSERVATIONS: Five patients were seen who had primary melanomas of both the eye and the skin. In three of these patients, the cutaneous melanomas were discovered only as a result of this study. The number of cutaneous melanomas expected in this cohort of patients with eye melanomas was no more than 0.4 on the basis of the United Kingdom incidence of both tumors. This difference was highly significant. CONCLUSIONS: The occurrence of primary cutaneous melanoma in five patients from a cohort of 207 patients with eye melanoma (or the premalignant melanocytic lesion of the conjunctiva called "primary acquired melanosis") provides strong evidence of an association between cutaneous and ocular melanoma. Three of the five patients also had the atypical mole syndrome phenotype, suggesting that the atypical mole syndrome predisposes to both types of melanoma.

Adult↗
PubMed1993

Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium.

Breast cancer is known to have an inherited component, consistent in some families with autosomal dominant inheritance; in such families the disease often occurs in association with ovarian cancer. Previous genetic linkage studies have established that in some such families disease occurrence is linked to markers on chromosome 17q. This paper reports the results of a collaborative linkage study involving 214 breast cancer families, including 57 breast-ovarian cancer families; this represents almost all the known families with 17q linkage data. Six markers on 17q, spanning approximately 30 cM, were typed in the families. The aims of the study were to define more precisely the localization of the disease gene, the extent of genetic heterogeneity and the characteristics of linked families and to estimate the penetrance of the 17q gene. Under the assumption of no genetic heterogeneity, the strongest linkage evidence was obtained with D17S588 (maximum LOD score [Zmax] = 21.68 at female recombination fraction [theta f] = .13) and D17S579 (Zmax = 13.02 at theta f = .16). Multipoint linkage analysis allowing for genetic heterogeneity provided evidence that the predisposing gene lies between the markers D17S588 and D17S250, an interval whose genetic length is estimated to be 8.3 cM in males and 18.0 cM in females. This position was supported over other intervals by odds of 66:1. The location of the gene with respect to D17S579 could not be determined unequivocally. Under the genetic model used in the analysis, the best estimate of the proportion of linked breast-ovarian cancer families was 1.0 (lower LOD-1 limit 0.79). In contrast, there was significant evidence of genetic heterogeneity among the families without ovarian cancer, with an estimated 45% being linked. These results suggest that a gene(s) on chromosome 17q accounts for the majority of families in which both early-onset breast cancer and ovarian cancer occur but that other genes predisposing to breast cancer exist. By examining the fit of the linkage data to different penetrance functions, the cumulative risk associated with the 17q gene was estimated to be 59% by age 50 years and 82% by age 70 years. The corresponding estimates for the breast-ovary families were 67% and 76%, and those for the families without ovarian cancer were 49% and 90%; these penetrance functions did not differ significantly from one another.

Adult↗
PubMed1993

Linkage analysis of early-onset breast and ovarian cancer families, with markers on the long arm of chromosome 17.

We have conducted linkage analysis in 16 breast cancer families, 13 of which are classified as site-specific breast cancer families and 3 of which are classified as breast-ovary families. Linkage analysis has largely focused on a single extended breast-ovary family. Analysis of all families combined shows significant evidence for linkage to 17q (LOD = 3.63 at theta = .0, for linkage to NME1), confirming the observations of Hall et al. and Narod et al. Many families were consistent with linkage, but their limited size and informativeness precluded confirmation of linkage. A putative recombinant in a breast-ovary family suggests that BRCA1 is distal to D17S250.

Adult↗
PubMed1992

Population genetics of colonic cancer.

BACKGROUND: There are several well known but rare syndromes of inherited colonic cancer. Genetic epidemiologic studies also have demonstrated that relatives of individuals with colonic cancer in general exhibit an excess risk for this malignancy. METHODS: This report reviews the literature pertinent to genetic and familial risk for colonic cancer with emphasis on the recent work that suggests that inherited susceptibility to colonic neoplasms is common. RESULTS: The adenomatous polyposis syndromes are rare inherited colonic cancer conditions caused by a mutant gene which recently has been characterized. Hereditary nonpolyposis colorectal cancer is likewise inherited and may account for up to 5% of cases. The molecular genetics of this disease remain to be clarified. The majority of colonic cancer cases are considered sporadic but are known to often cluster in families. Recent work suggests that inherited susceptibility may be the basis of this familial occurrence. Screening strategies based on inherited and familial risk are suggested. CONCLUSIONS: Knowledge of the familial and inherited risk for colonic cancer is leading to a better understanding of this disease and is suggesting more directed preventive strategies.

Adenomatous Polyposis Coli↗
PubMed1992

Hereditary aspects of colorectal adenomas.

BACKGROUND: Inheritance is important to the development of colonic adenomatous polyps and colon cancer. Current knowledge of inherited susceptibility to colonic neoplasms suggests that colon cancer screening strategies should consider familial and genetic risk. METHODS: This report reviews the literature pertinent to adenomatous polyp and colon cancer inheritance and suggests polyp-cancer screening procedures based on inherited or familial risk. RESULTS: Colorectal adenomas and cancer occur in several rare inherited syndromes and more commonly as sporadic cases. Intensive screening protocols have been suggested for the inherited syndromes because of the high associated cancer risk. Recent evidence suggests that inherited susceptibility also may be important in a large fraction of the so-called sporadic cases. Preliminary screening guidelines are suggested for this category based on the number of first-degree relatives affected with colon cancer. CONCLUSIONS: Inherited susceptibility appears to be more important to the pathogenesis of colorectal adenomas and cancer than previously recognized. Screening strategies which consider inherited risk may increase the effectiveness of cancer detection and prevention.

Adenoma↗