Books by International Agency for Research on Cancer

Records 22 papers presented at a meeting concerned with the design of prospective studies to investigate the role of diet and hormones in the etiology of cancer. The objective of the meeting was to identify methodological differences and common elements in both on-going and planned studies in order to facilitate the consolidation of data, communicate practical lessons about the advantages and pitfalls of different methodological approaches, and avoid duplication of efforts. Papers are presented in four main parts. The first describes on-going or planned prospective studies on diet and cancer at centres in the USA, Holland, Italy, France, Finland, Sweden, Denmark, and Poland. Papers in the second section, devoted to dietary assessment methods for epidemiological studies, communicate experiences in the use of dietary questionnaires and in methods for attenuating the problem of measurement error in nutritional epidemiology. Methodological problems in the use of biochemical, anthropometric and other measures of diet and nutritional status are considered in the third section. The book concludes with papers describing four prospective studies designed to determine the link between endogenous and exogenous hormones and cancers of the breast and female reproductive organs.

Evaluates the carcinogenic risks to humans posed by exposure to crystalline and amorphous silica, some silicates (palygorskite, sepiolite, wollastonite, and zeolites other than erionite), coal dust, and para-aramid fibrils. The volume opens with a discussion of the many complexities involved in assessing the cancer risks associated with occupational exposure to inhaled mineral dusts, and the special toxicological considerations required when evaluating the results of experimental studies. Against this background, the first and most extensive monograph evaluates human and animal carcinogenicity data on silica, concentrating on evidence of an increased risk for lung cancer. On the basis of this evaluation, crystalline silica inhaled in the form of quartz or cristobalite from occupational sources was classified as carcinogenic to humans. For amorphous silica, evidence from both epidemiological and experimental studies was judged inadequate, and amorphous silica could not be classified. For palygorskite, the evaluation found sufficient evidence from studies in rats that long fibres were carcinogenic; studies of exposure to short fibres showed no significant increase in the incidence of tumours. The few studies in humans were judged inadequate. Long palygorskite fibres were classified as possibly carcinogenic to humans. Short fibres could not be classified. For coal dust, several limitations in human studies, largely concerned with excessive mortality from lung and stomach cancer, hindered interpretation of the epidemiological literature. The few adequate experimental studies showed no increase in tumours. Coal dust therefore could not be classified. para-Aramid fibrils likewise could not be classifed in view of inadequates in both the epidemiological and experimental data.

Evaluates the carcinogenic risk to humans posed by the therapeutic use of thirteen pharmaceutical drugs, including eight benzodiazepines and related compounds used for the treatment of anxiety and as sedatives and anticonvulsants, three triphenylethylene anti-oestrogenic compounds developed for the treatment of breast cancer, and two cholesterol-lowering agents used to treat patients at high risk for cardiovascular disease. Evaluations are based on a critical assessment of all data available for these compounds, including abundant information on pharmacokinetic and pharmacodynamic effects, precise studies of exposure-response relationships, and findings that shed light on mechanisms of carcinogenic action. The most extensive monograph evaluates the large body of data on tamoxifen, which has been used for almost two decades as the first-line endocrine therapy for postmenopausal women with advanced metastatic breast cancer. Tamoxifen is also used as adjuvant therapy in patients with breast cancer and is being tested for use as a preventive agent. The evaluation found sufficient evidence in humans for the carcinogenicity of tamoxifen in increasing the risk for endometrial cancer, and conclusive evidence that tamoxifen reduces the risk for contralateral breast cancer in women with a previous diagnosis of breast cancer. Evidence for the carcinogenicity of tamoxifen in other organs was judged inadequate. Of the benzodiazepines, diazepam, which is the most widely prescribed, received the most extensive evaluation. Evidence reviewed suggested lack of carcinogenicity to the breast and inadequate evidence for carcinogenicity at other sites in humans. Diazepam could not be classified as to its carcinogenic risk to humans. Of the remaining benzodiazepines and related compounds, estazolam, prazepam, ripazepam, and temazepam could not be classified as to their carcinogenicity to humans. Oxazepam was classified as possible carcinogenic to humans on the basis of its carcinogenicity to rodents and uncertainty about extrapolation of experimental data to humans. Phenytoin, which has been widely used since the 1930s as an anticonvulsant in the treatment of epilepsy, was classified as possibly carcinogenic to humans. Of the remaining triphenylethylene anti-oestrogenic drugs developed for the treatment of breast cancer, neither toremifene, which is just being introduced, nor droloxifene, which is under development, could be classified. Likewise, data were judged inadequate for the classification of the two cholesterol-lowering drugs, clofibrate and gemfibrozil.

Evaluates the carcinogenic risk to humans posed by infection with human papillomaviruses (HPVs). To date, more than 70 HPV types have been identified, of which over 15 have been reported in cervical cancer biopsies. Although investigations of cervical cancer are most abundant, the report also considers the possible involvement of HPV infection in cancers at other sites, including the vulva, anus, skin, and aerodigestive tract. The first part summarizes what is known about the structure and molecular biology of papillomaviruses, and the epidemiology, pathology, and clinical management of HPV infections, including prospects for vaccine development. The main part evaluates the vast body of epidemiological studies investigating whether infection with HPV causes cervical cancer and cancers at several other cites. Findings from over 100 epidemiological case-control and cohort studies were considered. Evidence reviewed includes epidemiological studies conducted in the general population, studies of HPV and cancer conducted in special populations, including transplant patients and HIV-infected persons, and studies of skin cancer in patients with epidermodysplasia verruciformis. The studies provide compelling epidemiological evidence that some HPV types are human carcinogens, with HPVs detected in over 90% of all invasive cervical cancers. Part three cites experimental data supporting the carcinogenicity of specific HPV genotypes and elucidating the mechanisms by which HPV exerts its carcinogenic effects. The final part gives a summary and evaluation of all the available data. The report concludes that HPV types 16 and 18 are carcinogenic to humans. The report further concludes that HPV types 31and 33 are probably carcinogenic to humans, and that some HPV types other than 16, 18, 31 and 33 are possibly carcinogenic to humans.

Evaluates the carcinogenic risk to humans posed by occupational exposures to wood dust and formaldehyde. A number of occupational situations that involve exposure to wood dust also entail exposure to formaldehyde, as in plywood and particle board manufacture, during furniture and cabinet-making, and during parquet floor sanding and varnishing. The carcinogenic risks of wood dust are evaluated in the first monograph. The highest occupational exposures were noted to occur in wood furniture and cabinet manufacture, especially during machine sanding and similar operations, in the finishing departments of plywood and particle-board mills, and in the workroom air of sawmills and planer mills near chippers, saws, and planers. Citing findings from several recent well-designed case-control studies, the monograph concludes that occupational exposure to wood dust is causally related to adenocarcinoma of the nasal cavities and paranasal sinuses. The evaluation further concluded that the excess risk of cancer is attributable to wood dust per se, rather than to other exposures in the workplace. Wood dust was classified as carcinogenic to humans. Cancer risk associated with occupational exposure to formaldehyde is assessed in the second monograph. The assessment draws on findings from several cohort and case-control investigations of the relationship between exposure to formaldehyde and cancer of the oral cavity, pharynx, and respiratory tract. Citing inconsistencies in the reported results, the monograph concludes that these epidemiological studies can do no more than suggest a causal role of occupational exposure to formaldehyde in carcinoma of the nasal cavities and paranasal sinuses. The review found no evidence of excess risk for oropharyngeal, laryngeal or lung cancer among exposed workers. Several studies in which formaldehyde was administered to rats by inhalation showed evidence of carcinogenicity. Similar studies in hamsters showed no evidence of carcinogenicity, and studies in mice either showed no effect or were inadequate for evaluation. In rats administered formaldehyde in drinking-water, increased incidences were seen of forestomach papillomas in one study and of leukemias and gastrointestinal tract tumors in another; two other studies gave negative results. Formaldehyde was classified as probably carcinogenic to humans.