National Cancer Institute monograph最新文献

In vital statistics and most epidemiologic studies, cancers have been classified mostly by site of origin alone. This continues to be true even though it is continually being demonstrated that among cancers of a site important subsets with different epidemiologies almost always are present. Reasons for epidemiologists' failure to use all the information contained in the standard cancer classification are explored as are problems that arise from the nature of the classification, from the nature of the cancers being classified, and even from patient characteristics that determine how much information on the cancer can be gathered. The solution to the problem of too little information is generally difficult, but pathologists can say more about the epidemiologic implications of their various diagnoses and epidemiologists can learn to use these diagnoses in their cohort and other studies.

The historical developments leading to the acceptance of the influence of dietary and behavioral aspects of our life-style on cancer are reviewed. However, present information is usually insufficient to permit description of the complex mechanisms involved that are unlikely to yield to classical epidemiologic approaches alone. Better integrated laboratory epidemiologic studies are required that use more advanced nonintervention techniques. Progress may be slow in the identification of such factors in view of the many parameters involved, the absence of a single predominant or avoidable cause in many cancers, and the lack of adequately developed laboratory techniques for epidemiologic application.

The Framingham Heart Study, begun in 1948, had a cohort of 5,209 individuals who have been followed for 35 years. The selection of this population and the success in following it through biennial clinical examinations and indirect surveillance for deaths and hospitalizations are described. The major techniques used in analysis of the Framingham data are identified.

Procedures involving the use of computerized record linkage and national mortality and cancer incidence files for follow-up purposes in cohort studies which have been developed in Canada during the past decade are described. The results of some specific studies are presented as well as the advantages and limitations of such methods and the desirability for future research and development in this area.

The easy-to-use statistical package has imposed a new hardship on the clinical researcher: too much complicated analysis. The problem is most acute in the interpretation of multivariate results that select a combination of several factors that "best" predict or explain medical outcomes. For example, these methods give rise to formulas that 1) weigh together the risk factors of smoking, blood pressure, and lipid levels as determinants of heart disease, or 2) construct from pathologic and clinical evidence a prognostic profile for disease-free rectal cancer patients. To help the clinician apply these methods, we propose that, on request, statistical packages also produce two sets of calculations that validate the primary analysis: 1) a set of simple tabulations that show how the factors and outcomes used in the primary analysis relate to one another, and 2) the results of alternative analyses that show factors which every analysis selects, factors which only appear in the primary analysis, and those which tend to substitute for one another.

Through the use of molecular methods and mathematical models, epidemiologists are contributing to the improved understanding of the mechanisms of cancer. Multistage models with their mechanistic basis have been useful in descriptions of initiator-promoter type behavior of some carcinogens as well as genetic predisposition to rare tumors and reproductive risk factors in breast cancer. The use of biochemical and molecular laboratory techniques on tissue and fluid samples should provide important information in the near future concerning the basic mechanisms of human cancer. The potential of these methods is not only to describe exposure to carcinogens but also to indicate various host factors and their relevance to the risk of cancer.

The current standard for exposure to coke oven emissions sets a permissible exposure of 150 micrograms benzene-soluble fraction of total particulate matter/m3. The major epidemiologic study that formed the basis for this standard including a review of the evidence of a dose-response relationship between exposure to coal tar pitch volatiles and lung cancer is reviewed. Particular attention was given to the selection of the cohort, follow-up procedures, and the evolution of the analysis.

We initiated these studies to determine whether bifunctional (interstrand cross-linking) psoralens, such as 8-methoxypsoralen (8-MOP), are more carcinogenic than are the monofunctional, such as angelicin or isopsoralen derivatives, and 3-carbethoxysporalen (3-CP). Hairless mice (Skh:hr-1) in groups of 40 were treated three times weekly for 12 to 15 months. There were 17 groups, and the photocarcinogenic effects of 5 psoralens [8-MOP, 3-CP, 5-methylangelicin, 4,5'-dimethylangelicin (4,5'-DMA), and angelicin] were investigated. Ethanolic solutions of 0.01-0.1% psoralens were topically applied at 5.0 or 50 micrograms/cm2 from cervical to lumbar regions 45 minutes before exposure to UVA (320-400 nm) radiation (0.1, 2.5, or 7.5 joules/cm2). Control groups received either the drug application or UVA exposure only. The study revealed that isopsoralens, such as 5-methylangelicin or 4,5'-DMA, that form monofunctional adducts are more carcinogenic than bifunctional psoralens. The latency and time required for 50% prevelance of tumors was much longer with 8-MOP than with 4,5'-DMA or 5-methylangelicin. Mice treated with the latter 2 compounds had a greater number and larger tumors than mice treated with 8-MOP. The monofunctional angelicin was weakly carcinogenic, whereas 3-CP, also a monofunctional psoralen, was noncarcinogenic. Histologic examination revealed that tumors induced by 8-MOP, 5-methylangelicin, or 4,5'-DMA were all squamous cell carcinomas. Because of their skin-photosensitizing property and their ability to induce interstrand cross-links and severe damage to DNA in replication, bifunctional psoralens apparently produce more lethal damage in cells than do monofunctional isopsoralens.(ABSTRACT TRUNCATED AT 250 WORDS)

Skin cancers induced in mice by UVB, i.e., 280-320 nm radiation, are highly antigenic. They grow progressively in UVB-irradiated hosts because of certain specific immunologic alterations that are induced in the mice. Comparative studies of the immunologic aspects of carcinogenesis by UVB or methoxsalen plus UVA, i.e., 320-400 nm radiation (PUVA), formed the basis for the following conclusions: 1) Skin cancers induced by PUVA in C3H/HeN mammary tumor virus-negative mice are not highly antigenic, in contrast to those induced by UVB; 2) PUVA-induced tumors also differ from those induced by UVB, in that they do not exhibit preferential growth in UVB-irradiated mice; 3) PUVA treatment of mice, unlike UVB, does not induce susceptibility to the transplantation of UVB-induced tumors; 4) both UVB and PUVA treatments suppress the induction of contact hypersensitivity by a mechanism that involves suppressor lymphocytes.

Although severe biochemical and cytologic changes occur in both melanocytes and keratinocytes during psoralen photochemotherapy, a review of the published literature does not reveal any increased incidence of skin cancers from this type of therapy. Perhaps not enough time has elapsed to show such effects.