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Biomedical subjects

P Greenwald

Publications and source records attributed to P Greenwald.

At least 19 recordsLinked to original sources
PubMed1992

The study of markers of biological effect in cancer prevention research trials.

Biological markers may provide a valuable tool for the development of cancer prevention agents, for monitoring patient compliance to a selected intervention, or for further defining the carcinogenic process. This discussion focuses on markers of biological effect and the rationale for their use in cancer prevention trials. Recent studies with biological markers are investigating their incorporation into phase-I, -II, and -III chemoprevention clinical trial designs. Their use in clinical studies is expected to increase the number of agents that may be evaluated and to provide valuable information on the biological effectiveness of agents, doses, and schedules. Markers may also provide information to help in selecting high-risk groups for prevention research, and to indicate the pathways inhibited and the stage of carcinogenesis affected. Such information may prove of crucial importance in strengthening the rationale for long-term trials and other ancillary research. Biomarker research for colon carcinogenesis is discussed, including examples of a number of recent trials that may influence future progress in this area of prevention research. A crucial step in this process is marker validation as an aspect of major prospective observational and intervention studies where cancer incidence is the endpoint. We cannot be fully confident of markers as intermediate endpoints until the evidence from clinical trials is sufficiently strong to support major public health initiatives for prevention.

Antineoplastic Agents↗
PubMed1992

Colon cancer overview.

The scope of current prevention research support by the National Cancer Institute includes the clinical assessment of dietary modifications and cancer screening trials, epidemiologic studies, development of new chemopreventive therapies, and the use of advanced molecular biologic technologies to probe the genetic determinants of colorectal adenomas. Colorectal cancer frequently has been associated with high-fat low-fiber diets in epidemiologic and experimental studies. A recently initiated Phase III Dietary Intervention Study of Recurrence of Large Bowel Adenomatous Polyps will investigate the potential benefits of a low-fat high-fiber fruit-and-vegetable-enriched eating pattern to decrease the polyp recurrence rate. The Chemoprevention Program currently is supporting four Phase III controlled clinical intervention trials investigating the cancer-inhibiting effects on colorectal cancer of beta-carotene, piroxicam, calcium, and calcium plus fiber in persons with previous adenomas. A proposed early detection trial will screen for colorectal, prostate, lung, and ovarian cancers. A comparison of incidence and mortality trends indicates progress in colorectal cancer detection and therapy.

Anticarcinogenic Agents↗
PubMed1992

Role of biology and prevention in aerodigestive tract cancers.

Primary prevention aimed at smoking control and chemoprevention for high-risk persons or patients at risk for a second cancer provide strong potential for cancer prevention and control of aerodigestive cancers. The National Cancer Institute (NCI) has a major effort to build this area of research. The Third Upper Aerodigestive Tract Cancer Task Force Workshop, held in 1989 under the auspices of the National Cancer Institute's Organ System Program, reviewed the opportunities for chemoprevention research on aerodigestive epithelial cancers such as the regulation of growth and differentiation in normal and malignant cells. The chemoprevention program's drug development effort is evaluating several promising candidate agents for future clinical testing and the NCI clinical intervention program is supporting several trials of selected chemoprevention agents with demonstrated potential for inhibiting cancers of the lung, bronchus, oral cavity, and esophagus. Of special interest to this program is the assessment of beta-carotene, retinol and related synthetic retinoids, and several vitamin and mineral combinations under study in high-risk international populations. Chemoprevention in the medical setting is a major focus of NCI's Community Oncology Program (CCOP), a network designed not only to increase accrual of patients to trials but also to speed adoption of state-of-the-art therapies. Public health strategies are directed toward control of exposure to tobacco. The focal point for these activities is NCI's Smoking, Tobacco, and Cancer Program (STCP). STCP smoking cessation efforts are targeted at specific populations that are at greater risk for developing cancer including youth, minority and ethnic groups, women, smokeless tobacco users, and heavy smokers. Two of the world's largest controlled intervention trials conducted by the STCP are underway: the Community Intervention Trial for Smoking Cessation (COMMITT), which focuses on 6.5 million heavy smokers in 11 pairs of matched communities in North America, and the American Stop Smoking Intervention Study (ASSIST), a coalition model designed to reach millions of Americans through existing health promoting systems.

Adolescent↗
PubMed1992

Keynote address: cancer prevention.

Life-style factors that have a major impact on cancer risk are smoking, alcohol consumption, and diet. Current evidence suggests that dietary fat is an etiologic factor for colorectal and postmenopausal breast cancer and that foods high in dietary fiber may be beneficial against colorectal cancer. Clinical prevention trials, augmented by molecular and biological marker studies, will provide new knowledge for diet modification and chemoprevention. These studies are likely to influence the scope of oncology and public health practices of the future.

Breast Neoplasms↗
PubMed1991

Socioeconomic factors and cancer incidence among blacks and whites.

Findings from previous studies suggest that differences in socioeconomic status may be responsible for some, if not all, of the elevated incidence of cancer among blacks as compared with whites. Using incidence data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program, we tested this hypothesis by correlating black and white cancer incidence rates in three US metropolitan areas between 1978 and 1982 with data from the 1980 census on socioeconomic status within individual census tracts. The study analyzed data on the incidence of cancer at all sites combined (greater than 100 cancer sites) and at seven major sites separately. As in other studies, income and educational levels served as surrogates for socioeconomic status. The present study also used census-tract data on population density as a surrogate factor. Each of these measures of socioeconomic status was analyzed independently. Before correlation with census-tract data, age-adjusted data on cancer incidence showed statistically significant elevated risks among blacks for cancer at all sites combined and at four of the seven separate sites; whites showed an elevated risk for cancer at two sites. Cancer at only one site, the colon, showed no significant association with race. When age-adjusted incidence data were correlated with socioeconomic status, the comparative black-white risks changed: Whites showed an elevated risk of cancer at all sites combined and at three of the seven separate sites; blacks maintained their elevated risk at three sites. These findings suggest that the disproportionate distribution of blacks at lower socioeconomic levels accounts for much of the excess cancer burden among blacks. They also suggest that for both blacks and whites unidentified racial factors, which may be either cultural or genetic and which are not closely linked to socioeconomic status, may play a role in the incidence of some cancers.

Black or African American↗
PubMed1991

Issues in the early termination of the aspirin component of the Physicians' Health Study. Data Monitoring Board of the Physicians' Health Study.

The Physicians' Health Study is a randomized, double-blind, placebo-controlled prevention trial of 22,071 US physicians, using a factorial design to evaluate the role of aspirin in the prevention of cardiovascular mortality and beta carotene in the reduction of cancer incidence. After approximately 5 years of follow-up, the aspirin component was terminated, 3 years ahead of schedule. Several factors were considered in the decision to terminate, including a cardiovascular mortality rate markedly lower than expected in both aspirin and placebo subjects, precluding the evaluation of the primary aspirin hypothesis, and a highly significant (P < .00001) and impressive (44%) reduction in the risk of first myocardial infarction in the aspirin group. Issues in the decision to terminate are described in this report.

Adult↗
PubMed1990

Lung cancer and exposure to tobacco smoke in the household.

BACKGROUND: The relation between passive smoking and lung cancer is of great public health importance. Some previous studies have suggested that exposure to environmental tobacco smoke in the household can cause lung cancer, but others have found no effect. Smoking by the spouse has been the most commonly used measure of this exposure. METHODS: In order to determine whether lung cancer is associated with exposure to tobacco smoke within the household, we conducted a population-based case--control study of 191 patients with histologically confirmed primary lung cancer who had never smoked and an equal number of persons without lung cancer who had never smoked. Lifetime residential histories including information on exposure to environmental tobacco smoke were compiled and analyzed. Exposure was measured in terms of "smoker-years," determined by multiplying the number of years in each residence by the number of smokers in the household. RESULTS: Household exposure to 25 or more smoker-years during childhood and adolescence doubled the risk of lung cancer (odds ratio, 2.07; 95 percent confidence interval, 1.16 to 3.68). Approximately 15 percent of the control subjects who had never smoked reported this level of exposure. Household exposure of less than 25 smoker-years during childhood and adolescence did not increase the risk of lung cancer. Exposure to a spouse's smoking, which constituted less than one third of total household exposure on average, was not associated with an increase in risk. CONCLUSIONS: The possibility of recall bias and other methodologic problems may influence the results of case-control studies of environmental tobacco smoke. Nonetheless, our findings regarding exposure during early life suggest that approximately 17 percent of lung cancers among nonsmokers can be attributed to high levels of exposure to cigarette smoke during childhood and adolescence.

Adolescent↗
PubMed1990

Dietary fiber, vegetables, and colon cancer: critical review and meta-analyses of the epidemiologic evidence.

Whether colon cancer risk can be modified by a diet rich in vegetables, grains, and fruit, and, if so, whether the protective factor is dietary fiber or other biologically active components correlated with a high-fiber diet are questions of active research interest. Because studies on diet are susceptible to bias from a number of sources, in this review we evaluated the adequacy of study methodology as well as study results to clarify how much protection, if any, is conferred by a high-fiber diet. The review consisted of an aggregate assessment of the strength of evidence from 37 observational epidemiologic studies as well as meta-analyses of data from 16 of the 23 case-control studies. Both types of analyses revealed that the majority of studies gave support for a protective effect associated with fiber-rich diets; an estimated combined odds ratio (OR) of 0.57 (95% confidence interval = 0.50, 0.64) was obtained when the highest and lowest quantiles of intake were compared. Risk estimates based on vegetable consumption (OR = 0.48) were only slightly more convincing than those based on an estimate of fiber intake (OR = 0.58), but the data do not permit discrimination between effects due to fiber and nonfiber effects due to vegetables.

Case-Control Studies↗
PubMed1990

Concepts in cancer chemoprevention research.

Cancer prevention through the use of chemical intervention regimens (chemoprevention) is an emerging field with broad potential for impacting on cancer incidence rates in defined high-risk groups and the general population. Information from cancer epidemiologic studies coupled with that from basic research on cancer biology have combined to reveal several categories of agents with potential for clinical application, including natural and synthetic tumor suppressive retinoids and antioxidants. Chemopreventive agents may inhibit the development of cancer by limiting exposure to initiators or promoters through stimulation of inactivation or excretion mechanisms. Biological consequences of exposure to carcinogens may also be interfered with, e.g., by inhibiting the activation of proto-oncogenes or by antagonizing the effects of oncogene expression. Hundreds of compounds with chemopreventive efficacy in vitro have been isolated from foods and plant products. The testing and development of candidate chemopreventives proceeds through a series of preclinical efficacy screens, followed by controlled clinical trials.

Animals↗
PubMed1990

Strategies for cancer prevention through diet modification.

Diet and cancer research at the National Cancer Institute has grown from a budget of $2.5 million in 1974 to $55 million in 1988. The emphasis is partially on demonstrations of prevention strategies and chemoprevention trials. Studies to disseminate dietary goals in practical ways are undertaken with the aid of the food industry.

Diet↗
PubMed1979

Acquaintance networks among leukemia and lymphoma patients.

A case-control study of clustering through acquaintanceship among lymphoma and leukemia patients was conducted for the years 1967 through 1972 in Orleans County, New York. Twenty lymphoma and 17 leukemia cases met criteria for inclusion in the study. Data on acquaintanceship linkage were gathered from the source cases and controls, and from their acquaintances yielding a data base of 13,409 unique individuals linked by acquaintance. Three different analyses were carried out: a statistical analysis of linkage via intermediaries of case pairs in comparison with control pairs; a computer simulation of disease transmission from selected source cases to selected targets and controls based on the acquaintance data; and a secondary attack rate type analysis. The first two types of analysis yielded statistically significant case-control differences at the .05 level. The third method also yielded a positive result but was not subject to quantitative hypothesis testing. An additional conclusion is that these epidemiologic methods for disease with long induction periods merit further study.

Adolescent↗
PubMed1979

Estrogen and progestin binding in cytosols of ovarian adenocarcinomas.

Because a few ovarian adenocarcinomas respond favorably to endocrine therapy, we tested the hypothesis that some ovarian adenocarcinomas have functional similarity with sex-hormone-sensitive endometrial and breast tumors. Cytosols from 23 ovarian adenocarcinomas and 27 control tissues were examined for receptorlike estrogen and/or progestin binding. Eight of 16 primary ovarian adenocarcinomas had estrogen and/or progestin receptorlike components; among the metastases tested, one third retained estrogen binding. No correlations were found between binding characteristics and histopathologic grade. The presence of estrogen binding in a lung lesion helped confirm recurrent ovarian disease. Estrogen binding occurred in specimens from women with no histories of exposure to exogenous estrogen. Because tamoxifen and nafoxidine could inhibit estradiol binding, it is likely that antiestrogens will prove beneficial against some ovarian cancers.

Adenocarcinoma↗