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J S Witte

Publications and source records attributed to J S Witte.

At least 37 records · Page 2Linked to original sources
PubMed1999

Model-based and model-free multipoint genome-wide linkage analysis of alcoholism.

We analyzed a subset of the Collaborative Study on the Genetics of Alcoholism (COGA) data set as provided by the 11th Genetic Analysis Workshop (GAW11). Linkage analyses were performed using each of the diagnostic criteria for alcoholism included in the data: the COGA criteria (DSM-III-R plus the Feighner criteria) and the narrower World Health Organization diagnosis ICD-10 criteria. Formal segregation analysis using these data was not attempted because only a subset of all the originally ascertained families was made available. Nevertheless, an attempt was made to estimate the best one-locus two-allele genetic model for these data. Model-based multipoint linkage analysis was performed using the results of our trait model fitting, and model-free multipoint linkage analysis was performed with an improved version of the Haseman and Elston linkage method for sib pairs.

Adolescent↗
PubMed1999

Family-based association studies.

We review case-control designs for studying gene associations in which relatives of case patients are used as control subjects. These designs have the advantage that they avoid the problem of population stratification that can lead to spurious associations with noncausal genes. We focus on designs that use sibling, cousin, or pseudosibling controls, the latter formed as the set of genotypes not transmitted to the case from his or her parents. We describe a common conditional likelihood framework for use in analyzing data from any of these designs and review what is known about the validity of the various design and analysis combinations for estimating the genetic relative risk. We also present comparisons of efficiency for each of the family-based designs relative to the standard population-control design in which unrelated controls are selected from the source population of cases. Because of overmatching on genotype, the use of sibling controls leads to estimates of genetic relative risk that are approximately half as efficient as those obtained with the use of population controls, while relative efficiency for cousin controls is approximately 90%. However, we find that, for a rare gene, the sibling-control design can lead to improved efficiency for estimating a G x E interaction effect. We also review some restricted designs that can substantially improve efficiency, e.g., restriction of the sample to case-sibling pairs with an affected parent. We conclude that family-based case-control studies are an attractive alternative to population-based case-control designs using unrelated control subjects.

Case-Control Studies↗
PubMed1999

The health effects of swimming in ocean water contaminated by storm drain runoff.

Waters adjacent to the County of Los Angeles (CA) receive untreated runoff from a series of storm drains year round. Many other coastal areas face a similar situation. To our knowledge, there has not been a large-scale epidemiologic study of persons who swim in marine waters subject to such runoff. We report here results of a cohort study conducted to investigate this issue. Measures of exposure included distance from the storm drain, selected bacterial indicators (total and fecal coliforms, enterococci, and Escherichia coli), and a direct measure of enteric viruses. We found higher risks of a broad range of symptoms, including both upper respiratory and gastrointestinal, for subjects swimming (a) closer to storm drains, (b) in water with high levels of single bacterial indicators and a low ratio of total to fecal coliforms, and (c) in water where enteric viruses were detected. The strength and consistency of the associations we observed across various measures of exposure imply that there may be an increased risk of adverse health outcomes associated with swimming in ocean water that is contaminated with untreated urban runoff.

California↗
PubMed1999

Association between a CYP3A4 genetic variant and clinical presentation in African-American prostate cancer patients.

Prostate cancer incidence, clinical presentation, and mortality rates vary among different ethnic groups. A genetic variant of CYP3A4, a gene involved in the oxidative deactivation of testosterone, has been associated recently with prostate cancer development in Caucasians. To further investigate this variant, we evaluated its genotype frequencies in different ethnic groups and its association with clinical presentation of prostate cancer in African Americans. CYP3A4 genotypes were assayed in healthy male Caucasian (n = 117), Hispanic (n = 121), African-American (n = 116), Chinese (n = 46), and Japanese (n = 34) volunteers using the TaqMan assay. The association between CYP3A4 genotype and prostate cancer presentation was determined in 174 affected African-American men. Genotype frequency of the CYP3A4 variant differed substantially across ethnic groups, with African Americans much more likely to carry one or two copies than any other group (two-sided P < 0.0001). Among African Americans, 46% (80 of 174) of men with prostate cancer were homozygous for the CYP3A4 variant, whereas only 28% (32 of 116) of African-American healthy volunteers were homozygous (two-sided P < 0.005). A consistent positive association was observed between being homozygous for the CYP3A4 variant in African-American prostate cancer patients and clinical characteristics. Men homozygous for the CYP3A4 variant were more likely to present with higher grade and stage of prostate cancer in a recessive model [odds ratio (OR), 1.7; 95% confidence interval (CI), 0.9-3.4]. This association was even stronger for men who were >65 years of age at diagnosis (n = 103; OR, 2.4; 95% CI, 1.1-5.4). In summary, the CYP3A4 genotype frequency in different ethnic groups broadly followed trends in prostate cancer incidence, presentation, and mortality in the United States. African-American prostate cancer patients had a higher frequency of being homozygous for the CYP3A4 variant than healthy African-American volunteers who were matched solely based on ethnicity. Among the patients, those who were homozygous for the CYP3A4 variant were more likely to present with clinically more advanced prostate cancer.

Adult↗
PubMed1998

Evaluating the performance of a genetic test using information from previous studies in place of a gold standard.

OBJECTIVES: To evaluate the performance of a diagnostic test, a researcher usually must classify study subjects with respect to (1) whether the test result was positive or negative and (2) whether the test result should have been positive or negative. To classify the subjects in the second manner, the researcher needs to have access to a gold standard (ie, a test that classifies the subjects with 100% accuracy). The authors show here how to evaluate the performance of a diagnostic test that allows researchers to determine whether a disease that is occurring within a family is attributable to one of two newly discovered genes without the use of a gold standard. METHODS: By taking advantage of well-known genetic phenomena and their statistical implications, the behavior of the diagnostic test is mathematically modeled, and its performance with respect to various criteria is shown to be functions of genetic parameters. RESULTS: The performance of the test over a wide range of values of the genetic parameters was evaluated, and cutoff points that would allow the test to perform very well or well with respect to all criteria were found for almost all of the situations examined. CONCLUSIONS: This test can be used effectively under a wide range of conditions. In addition, because the genetic parameters have been estimated in previous studies, the effectiveness of the test for the specific conditions the researcher may need to run the study under can be evaluated before the study is performed.

Breast Neoplasms↗
PubMed1998

Glutathione transferase null genotype, broccoli, and lower prevalence of colorectal adenomas.

Cruciferous vegetables, especially broccoli, may prevent cancer through anticarcinogenic compounds. For example, broccoli contains isothiocyanates that induce carcinogen-detoxifying enzymes. Glutathione transferase enzymes conjugate isothiocyanates, leading to excretion. We hypothesized that broccoli consumption in combination with the glutathione transferase M1 (GSTM1) null genotype would be associated with a lower prevalence of colorectal adenomas because of higher isothiocyanate levels. We used a case-control study of mainly asymptomatic subjects aged 50-74 years who underwent a screening sigmoidoscopy at either of two Southern California Kaiser Permanente Medical Centers during 1991-1993. Cases (n = 459) had a first-time diagnosis of histologically confirmed adenomas detected by flexible sigmoidoscopy. Controls (n = 507) had no polyp detected. Subjects had a 45-min in-person interview for information on various risk factors and basic demographic data and completed a 126-item, semiquantitative food frequency questionnaire. Blood samples were used for GSTM1 genotyping. Subjects with the highest quartile of broccoli intake (an average of 3.7 servings per week) had an odds ratio of 0.47 (95% confidence interval, 0.30-0.73) for colorectal adenomas, compared with subjects who reportedly never ate broccoli. When stratified by GSTM1 genotype, a protective effect of broccoli was observed only among subjects with the GSTM1 null genotype (P for trend, 0.001; P for interaction, 0.01). The observed broccoli-GSTM1 interaction is compatible with an isothiocyanate mechanism.

Adenoma↗
PubMed1998

Software for hierarchical modeling of epidemiologic data.

Hierarchical models can provide more reasonable and stable parameter estimates than conventional analytical approaches. This technique also deals with problems of multiple comparisons and allows one to model multilevel data within a hierarchical framework. Hence, one would anticipate a surge in applying hierarchical models to epidemiologic data. Difficulties in fitting hierarchical models, however, seem to have limited their use. To help address this problem, we describe the existing software packages that one can use to fit hierarchical models. Since these packages have limited familiarity and applicability in epidemiology, we also present SAS code for analyzing epidemiologic data with hierarchical models. These results allow epidemiologists to fit hierarchical models with readily available software.

Breast Neoplasms↗
PubMed1997

A sigmoidoscopy-based case-control study of polyps: macronutrients, fiber and meat consumption.

We conducted a large, sigmoidoscopy-based case-control study to examine the relation of intake of macronutrients, meat, and fiber to occurrence of adenomas of the large bowel. Cases were subjects diagnosed for the first time with one or more histologically confirmed adenomas. Controls had no polyps of any type at sigmoidoscopy, had no history of polyps, and were individually matched to cases by gender, age, date of sigmoidoscopy, and Kaiser Center. The response rate was 84% for cases and 82% for controls. Complete dietary data for 488 matched pairs were available. All odds ratios are from matched analyses adjusted for energy. We observed positive associations with risk of adenomas for calories, animal fat, saturated fat, red meat, and the ratio of red meat to poultry and fish. Protective effects were observed for vegetable protein, carbohydrates, and dietary fiber. The fiber effects diminished after adjusting for fruits and vegetables. Results after mutually adjusting for the effects of saturated fat, fiber and the ratio of red meat to chicken and fish suggest that each of these variables has an effect on risk of adenomas that is independent of the other 2 exposures.

Aged↗
PubMed1997

Plasma carotenoids and the prevalence of adenomatous polyps of the distal colon and rectum.

In a case-control study, the authors investigated relations between plasma carotenoid concentrations and the prevalence of colorectal adenomatous polyps (precursors to colorectal cancer) in residents of Los Angeles County and Orange County, California, from 1991 through 1993. Plasma concentrations of six carotenoids were compared in 472 asymptomatic cases with a first-time diagnosis of at least one adenomatous polyp of the distal colon or rectum and 502 matched controls. Odds ratios adjusted for age, sex, smoking, alcohol intake, and energy, saturated fat, and fruit and vegetable intake revealed no associations between any of the individual carotenoids and polyp prevalence or between total carotenoids and polyp prevalence.

Adenomatous Polyps↗
PubMed1997

Genetic analysis with hierarchical models.

During the Genetic Analysis Workshop 9 presentations [Goldin et al., 1995] a brief discussion took place about the value of empirical-Bayes methods in genetic analysis. Due to the informal nature of this discussion, the improvements available for analyzing data with this approach--and with the broader class of hierarchical models--were not clearly presented. As a methodologic contribution, I further explore how one can use this potentially valuable technique in analysis of genetic data, including data similar to those given in GAW10.

Bayes Theorem↗
PubMed1997

Modeling age of onset and residual familial correlations for the linkage analysis of bipolar disorder.

We applied regressive modeling to the data described by Stine et al. [1995] and further explored the possible linkage of bipolar disorder to marker D18S41 on chromosome 18. We performed analyses to determine age-dependent penetrance functions that best fit the data and that allow for residual familial correlations. Specifically, we introduce here a simple method to allow for a sibling correlations. that is not due to segregation at the linked locus, and then extend the results of Stine et al. [1995] by using the best fitting "regressive" model of this kind as input into a lod score linkage analysis. Although a formal segregation analysis was not attempted, a surprising finding was that, except for doubtful linkage to D18S41, there is little evidence for genetic transmission of bipolar disorder in these families.

Age of Onset↗
PubMed1997

Familial prostate cancer: a different disease?

PURPOSE: We analyzed the outcome after radical prostatectomy of patients with familial prostate cancer versus patients with sporadic prostate cancer. MATERIALS AND METHODS: The study included 720 patients with prostate carcinoma who were treated with prostatectomy between 1987 and 1996. Patients were excluded from the study if they had received adjuvant or neoadjuvant treatment, or had no available pretreatment prostatic specific antigen (PSA) level, no available biopsy Gleason score, incomplete pathological information or no available followup PSA levels. The analysis was performed on 529 cases. Patients were considered to have a positive family history for prostate cancer when the index patient confirmed the diagnosis of prostate cancer in a first degree relative (brother or father). The outcomes of interest were biochemical relapse-free survival, local failure and distant metastases. Proportional hazards were used to analyze the effect of family history and confounding variables (that is age, stage, biopsy Gleason score, initial PSA levels, surgical specimen Gleason score, extracapsular extension, lymph node metastasis, seminal vesicle invasion and surgical margin involvement) on treatment outcome. RESULTS: Median followup was 30 months. Of all cases 12% had a positive family history. Younger age was the only factor associated with positive family history, with 18% of patients younger than 65 years having a positive family history versus 6% of older patients (chi-square p <0.001). The 5-year biochemical relapse-free survival rate for the entire group was 64%. The 5-year biochemical relapse-free survival rates for patients with negative family history versus positive history were 66% and 46%, respectively (p = 0.001). A multivariate time-to-failure analysis using the proportional hazards model was performed based on family history, age (less than 65 versus 65 to 69 versus 70 or greater, initial PSA (10 or less versus greater than 10), biopsy Gleason score (6 or less versus 7 or greater), clinical T stage (T1-T2A versus T2B-C), prostatectomy specimen Gleason score (6 or less versus 7 or greater), extracapsular extension, seminal vesicle involvement, surgical margin involvement and lymph node involvement. After adjusting for the potential confounding factors, positive family history remained strongly associated with biochemical failure. The clinical failure rate for the entire group was 14%. The 5-year local failure rate was 7%, with positive surgical margins being the only independent predictor of local failure. The 5-year distant metastasis rate was 8%, with family history and initial PSA levels being independent predictors of distant relapse. CONCLUSIONS: Our study suggests that patients with a familial prostate cancer have a higher likelihood of biochemical failure after radical prostatectomy than patients with sporadic cancer. This effect is independent of pretreatment or pathological factors. Our results suggest that the higher failure rates associated with familial prostate cancer are mainly secondary to higher distant relapse rates, and that familial prostate cancer may be more biologically aggressive than sporadic cancers.

Adenocarcinoma↗
PubMed1997

A nested approach to evaluating dose-response and trend.

PURPOSE: Conventional dose-response and trend analysis fits either a linear or categorical logistic model and tests the resulting coefficients. These analyses, however, are based on implausible assumptions. METHODS: We present an alternative approach that uses likelihood ratio tests to compare nested regression models and determine when a model is rich enough to capture the data trends. RESULTS: For illustration, we apply this approach to data on diet and colorectal polyps. CONCLUSIONS: Comparison of linear and quadratic spline logistic models indicates that the conventional approach of using only a linear logistic model would not appropriately describe the association between intake of fruits and vegetables and colorectal polyps in our data. Graphical checking further supports this conclusion.

Case-Control Studies↗
PubMed1997

Diet and premenopausal bilateral breast cancer: a case-control study.

We investigated associations between diet and premenopausal bilateral breast cancer in a familial matched case-control study. We studied 140 cases from population-based registries in Los Angeles County (California) and Connecticut, and from the major hospitals in the southern parts of the Province of Quebec. Unaffected sisters of the cases served as matched controls (222 total). Dietary intake were assessed with a food frequency questionnaire. Total fat, monounsaturated fat, polyunsaturated fat, oleic acid, and linoleic acid intake was inversely associated with premenopausal bilateral breast cancer risk. Consumption of carbohydrates (and sweetened beverages) was associated with an increased risk. We observed no associations for dietary fiber, antioxidants, or major food groupings, but we did observe inverse associations for intake of low fat dairy products and tofu. These findings suggest that monounsaturated and polyunsaturated fats, as well as soy foods, might reduce the risk of premenopausal bilateral breast cancer.

Adult↗
PubMed1997

Meat preparation and colorectal adenomas in a large sigmoidoscopy-based case-control study in California (United States).

The often observed association between red meat and colorectal cancer could be due in part to mutagens, such as heterocyclic amines (HCA), that are present in cooked meat. HCAs are highly mutagenic and cause intestinal tumors in animals. The hypothesis that HCAs are also carcinogenic to humans remains to be substantiated in epidemiologic studies. We determined the associations of meat preparation and frequency of intake (proxy variables for HCA exposure, since HCA concentration depends on the type of meat and the way it is cooked) with the prevalence of distal colorectal adenomas in a sigmoidoscopy-based case-control study of 488 matched pairs of subjects from two California (United States) Kaiser Permanente Medical Centers. A more than twofold difference in adenoma prevalence between subjects at extreme ends of estimated HCA intake was observed. For subjects who ate red meat more than once per week, fried it more than 10 percent of the time, and ate it with a darkly browned surface, compared with subjects who ate red meat one time or less per week, fried it 10 or less percent of the time, and ate it with a lightly browned surface, the odds ratio was 2.2 (95 percent confidence interval = 1.1-4.3). Adenoma prevalence also increased with frequency of frying red meat (P trend = 0.004). These results are consistent with a carcinogenic effect of HCA.

Adenoma↗