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D T Bishop

Publications and source records attributed to D T Bishop.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Frequency of familial colorectal cancer.

Familial clustering of cancer is not uncommon. The frequency of familial colorectal cancer was estimated by taking family histories from 100 patients presenting with apparently sporadic colorectal cancer. Compared with controls, the relative risk of a positive family history for colorectal cancer was 4.6. Life-table methods were used to examine the observed to expected mortality from colorectal cancer. Overall there was a fourfold increase in mortality rate (P less than 0.0001), which was greatest in female relatives of patients with colonic cancer (P less than 0.001). Three families with dominant inheritance of colorectal cancer and one family with Lynch type II syndrome were identified. Nine per cent of patients had siblings who had developed colorectal cancer a median of 4 years before the diagnosis of the index patient (range 1-17 years). It is recommended that a careful family history should be obtained from all patients with colorectal cancer. Where a positive history is obtained a geneticist may determine empirical risks for the development of colorectal cancer and the appropriate method of surveillance may be selected.

Adult↗
PubMed1990

The genetics of colorectal cancer.

Two features of colorectal cancer have greatly aided the recent progress in understanding its genetics: firstly the majority of colorectal cancers arise from premalignant adenomatous polyps allowing the analysis of somatic genetic changes during tumorigenesis, and secondly there are several well defined inherited syndromes that predispose to colorectal cancer in an autosomal dominant manner. The familial polyposis gene has been mapped to chromosome 5q and loss of material on chromosome 5 shown in a large proportion of sporadic (non-familial) adenomas and carcinomas. Allele loss has also been found in a high proportion of colorectal cancers on chromosomes 17 and 18 and the respective genes involved identified as that coding for the oncoprotein p53 on 17p and the DCC ('deleted in colorectal carcinomas') gene on 18q. In addition activation of k-ras is found frequently in colorectal adenomas and carcinomas. The development of colorectal neoplasia is associated with the accumulation of genetic changes. Family studies of apparently sporadic colorectal cancer probands have shown an increased incidence of adenomas and carcinomas in first degree relatives. More recently pedigree studies have suggested that an inherited predisposition may be responsible for the majority of colorectal tumours.

Chromosome Aberrations↗
PubMed1990

Risk and surveillance of individuals with heritable factors for colorectal cancer. WHO Collaborating Centre for the Prevention of Colorectal Cancer.

Heritable and genetic factors pertinent to colon cancer can be divided into three categories: inherited syndromes, genetic epidemiology, and molecular genetics. Familial adenomatous polyposis (FAP) and Gardner syndrome (GS) are rare dominantly inherited syndromes characterized by hundreds to thousands of colonic adenomatous polyps. Colon cancer occurs at a young age in both diseases unless the colon is removed. Peutz-Jeghers syndrome and familial juvenile polyposis are inherited hamartomatous polyposis conditions with a less dramatic, but definite, increased risk for colon cancer. These four polyposis syndromes together account for less than 1% of cases of colon malignancy. Hereditary nonpolyposis colorectal cancer is a dominantly inherited form of colon cancer characterized by an early age of onset and a predilection for proximal colonic tumours. Multiple primary malignancies are frequently observed and one or several adenomatous polyps are often present in affected individuals; 4-6% of colon cancer cases occur in relationship to this syndrome. Genetic epidemiological studies have consistently shown that first-degree relatives of persons with colon cancer have a twofold to threefold increased risk of having colon malignancy. More recent studies have found a similar risk among relatives of those with adenomatous polyps. Studies of colon cancer and adenomatous polyps in pedigrees have further demonstrated that this familial clustering probably occurs on the basis of partially penetrant inherited susceptibilities. These inherited susceptibilities probably interact with environmental factors to give rise to polyp growth and finally colon cancer. Molecular studies have begun to elucidate the genetic mechanisms of colon cancer at the DNA level. The germinal mutation of FAP and GS has been localized to the long arm of chromosome 5. Tissue samples from "random" adenomatous polyps and colon cancers have shown frequent and specific acquired DNA sequence deletions on chromosomes 5, 17, and 18. Mutations and over-expression of the ras oncogene likewise have been observed in such tissues. The chromosome 5 defect in polyp and cancer tissues is probably at the same locus as the germinal mutation of FAP. There is evidence that this locus normally regulates expression of the c-myc oncogene, which in turn probably has a regulatory function in DNA replication. The chromosome 17 deletion is a mutation of the gene for the transformation-associated protein, p53. Appropriate screening starting at a relatively young age is necessary to prevent cancer in the inherited syndromes. Screening is also indicated in close relatives of those with nonsyndromic or common colon cancer in view of the moderately increased risk for colon cancer in this group.(ABSTRACT TRUNCATED AT 400 WORDS)

Colorectal Neoplasms↗
PubMed1990

The power of identity-by-state methods for linkage analysis.

The affected-sib-pair method has been widely utilized for mapping. This methodology is aimed at mapping complex traits which have been observed to be familial but for which Mendelian segregation, even after allowing for partial penetrance, is not apparent. Indications of linkage are based on the observation of nonrandom segregation at a marker locus in two affected siblings. We extend this methodology to more distant genetic relationships and examine the power of identity-by-state methods for mapping when marker information is only available on pairs of affected relatives. The power depends on the polymorphism of the marker, the probability of identity by descent at the trait locus, and the recombination fraction between the trait and the marker loci.

Female↗
PubMed1989

Characteristics of familial colon cancer in a large population data base.

Early age onset and proximal colonic location are two specific characteristics of colon cancer which have been used clinically to assess the risk that an individual case is of familial rather than sporadic origin. This practice derives from the observation that these characteristics are typical of the rare, nonpolyposis inherited colorectal cancer syndromes. This study examines these two characteristics in cases of common colon cancer to determine whether they actually distinguish individuals at increased risk for familial colorectal cancer. Familial clusters of colon cancer in the Utah Population Data Base were examined. Common colon cancers were found to cluster excessively in families; however, the measure of familial clustering for distal colonic cases was increased to the same degree as proximal colonic cases. Early age onset was likewise not a distinguishing factor of familial cases. These results suggest that factors other than those that predispose to the rare syndromes are important in determining familial risk for common colon cancers, and that the absence of these two clinical features should not suggest the absence of familial risk of colorectal cancer.

Adult↗
PubMed1989

Relationship between body mass index, cigarette smoking, and plasma sex steroids in normal male twins.

Smoking has been observed to affect plasma sex hormones and body mass index. The relationship between smoking, body mass index, and plasma concentration of sex hormones was studied in normal adult male twins. The analyses were performed for between 150 and 159 twin pairs for whom hormonal data were available on both twins. With bivariate analysis, neither body mass index nor smoking affected estrone, luteinizing hormone, follicle-stimulating hormone, ratio of testosterone to estradiol, or ratio of testosterone to dihydrotestosterone. Body mass index significantly (P less than 0.05) affected sex hormone binding globulin, whereas smoking had no effect. The plasma contents of testosterone and dihydrotestosterone and the luteinizing hormone/testosterone ratio were affected by both body mass index and smoking, although, after allowing for body mass, smoking was less significant (0.05 less than P less than 0.10). A path model was formulated to examine the relationship of body mass and sex steroid levels. Our results suggest that body mass index affects sex steroids, since common environmental factors do not account for the strength of the relationship. The bivariate analysis suggests that the smoking effect on sex hormones (except perhaps for dihydrotestosterone) is secondary to an effect on body mass index.

Adult↗