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D T Bishop

Publications and source records attributed to D T Bishop.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1988

Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers.

We studied 670 persons in 34 kindreds by flexible proctosigmoidoscopic examination (60 cm) to determine how frequently colorectal adenomas and cancers result from an inherited susceptibility. Kindreds were selected through either a single person with an adenomatous polyp or a cluster of relatives with colonic cancer. The kindreds all had common colorectal cancers, not the rare inherited conditions familial polyposis coli and nonpolyposis inherited colorectal cancer. Likelihood analysis strongly supported the dominant inheritance of a susceptibility to colorectal adenomas and cancers, with a gene frequency of 19 percent. According to the most likely genetic model, adenomatous polyps and colorectal cancers occur only in genetically susceptible persons; however, the 95 percent confidence interval for this proportion was 53 to 100 percent. These results suggest that an inherited susceptibility to colonic adenomatous polyps and colorectal cancer is common and that it is responsible for the majority of colonic neoplasms observed clinically. The results also reinforce suggestions that first-degree relatives of patients with colorectal cancer should be screened for colonic tumors. This evidence of an inherited susceptibility to a cancer with well-recognized environmental risk factors supports the hypothesis that genetic and environmental factors interact in the formation and transformation of polyps.

Adenomatous Polyposis Coli↗
PubMed1988

The effect of nutritional factors on sex hormone levels in male twins.

Dietary intake has been hypothesized as being associated with several hormonally related cancers including prostate, breast, ovarian, and endometrial cancer. Because diet may affect hormones directly, it is logical to examine the effects of dietary factors on hormone production and levels. Therefore, a set of 72 male MZ and 83 male DZ twin pairs was ascertained from the Utah birth certificates. A quantitative food frequency questionnaire was administered and blood samples were drawn for hormonal assays. Heritability estimates for hormonal levels were calculated indicating a range from no heritability for sex hormone binding globulin (SHBG), estrone, and testosterone glucuronide to 70% for androstanediol glucuronide and luteinizing hormone. To examine nutritional factors, the difference in hormone and SHBG levels between each MZ twin and his co-twin were correlated with the difference in nutrient intake. Weight and obesity were significantly correlated with plasma testosterone and follicle stimulating hormone. Fat intake showed a significant association with testosterone. Androstanediol glucuronide, a steroid that reflects tissue formation of dihydrotestosterone, was inversely correlated with caloric intake, theobromine and caffeine. Testosterone glucuronide exhibited significant correlations with calories and vitamin A. This study suggests that dietary intake affects plasma sex-steroid levels in men.

Diet↗
PubMed1988

Linkage information and bias in the presence of interference.

Although interference is an important biological phenomenon, linkage analyses often ignore it for computational efficiency. In this paper we examine the effects of ignoring interference on estimates of recombination fraction, and the power of statistical tests to detect interference. We show that for gametes from phase-known triple heterozygotes, no bias in the recombination fraction for adjacent loci results from the assumption of lack of interference even if interference is present. However, for samples from pairwise informative samples, there is bias introduced. An analytical form for this bias is obtained.

Chromosome Mapping↗
PubMed1988

Segregation and linkage analysis of nine Utah breast cancer pedigrees.

The analysis of nine Utah families that were ascertained for clusters of breast cancer cases is reported. Segregation analysis of an inherited susceptibility to breast cancer shows two distinct maximum likelihood solutions that have almost equal likelihood. One model indicates that most females had zero risk for breast cancer, but 10% of the female population had risks much greater than the Utah age-specific incidence rates. The other model indicates that most females have a risk defined by the Utah rates for breast cancer, but a rare dominant gene is segregating for increased susceptibility to breast cancer. Our analysis shows that linkage results under the two models are consistent in sign but not in magnitude. No evidence for linkage was found with the 14 marker loci examined. In addition to demonstrating distortion of linkage results from ignoring sporadic cases, this analysis shows the inherent difficulty of obtaining parameter estimates for segregation analysis when families are ascertained from a cluster of cases.

Breast Neoplasms↗
PubMed1988

Lifestyle and blood pressure levels in male twins in Utah.

Healthy male monozygotic (MZ) and dizygotic (DZ) twin pairs (MZ pairs = 77; DZ pairs = 88) were studied to assess the effect of dietary intake, physical activity, physical fitness, body mass index (BMI), sum of the triceps and subscapular skinfold measurements, alcohol and caffeine consumption, and smoking patterns on blood pressure. Data on physical activity, detailed dietary intake, medical history, and demographics were obtained from a questionnaire. A bicycle ergometer was used to estimate level of fitness; other medical information was ascertained from physical examination. After normalizing the study variables, intraclass correlations for BMI and the sum of the triceps and subscapular skinfold measurements were higher in MZ than in DZ twin pairs (BMI: MZ r = 0.76, DZ r = 0.48; skinfolds: MZ r = 0.73, DZ r = 0.28), as were VO2max(MZ r = 0.63, DZ r = 0.25) and post-bike heart rate (MZ r = 0.69, DZ r = 0.19). Both systolic (SBP) and diastolic blood pressure (DBP) had high heritability estimates (SBP = 0.60, and DBP = 0.66). Using factor analysis, four major lifestyle factors were identified and categorized as: 1) dietary intake; 2) a factor heavily weighted by cigarette smoking, alcohol and caffeine consumption; 3) fatness; 4) physical activity and physical fitness. Adjustment for these factors did not alter heritability estimates for either SBP or DBP.

Blood Pressure↗
PubMed1988

Heritability of variation of plasma cortisol levels.

Heritability of the variation of the plasma concentrations of total and unbound cortisol, cortisol binding globulin (CBG), and dehydroepiandrosterone sulfate (DHEA-S) was investigated in 20 monozygotic (MZ) and 20 dizygotic (DZ) male twin pairs. Three plasma samples collected between 8 AM and 9:30 AM were pooled for the assays. Heritability was calculated from the intraclass correlation [2(rMZ - rDZ)]. The mean age, total and unbound cortisol, CBG, and DHEA-S were not significantly different between the MZ and DZ groups of twins. The heritability index for variability of the plasma content of steroids was 45.4% (p less than .05) for total cortisol, 50.6% (P less than .05) for unbound plasma cortisol, 57.8% (P less than .05) for DHEA-S, and 32.4% (P greater than .05) for CBG. The data were analyzed by factor analysis, and heritability estimates were corrected for factors including age, smoking, drinking, exercise, and degree of obesity. These factors did not account for the variation in hormone values in twin pairs. Factor analysis of the three quantitative measurements, cortisol, percent free cortisol, and DHEA-S, provides no evidence for shared factors. The correlation coefficients between age and CBG and total and unbound plasma cortisol concentrations were insignificant. The correlation coefficient between total plasma cortisol levels and CBG was 0.57, which indicates that CBG accounts for 32% of the variation of plasma cortisol concentrations. The results suggest that genetic factors have a decided influence on the variation of the concentration of cortisol of DHEA-S in normal adult men.

Age Factors↗