Victor E. Archer

Cytologic examinations of sputum collected periodically since 1957 on a group of uranium miners have been studied and related to the development of bronchogenic carcinoma. Many individuals developed abnormal squamous cell metaplasia that gradually progressed, in several, to develop invasive carcinoma. This progression has been classified into mild, moderate, and marked atypical, squamous cell metaplasias and carcinoma in situ. Cigarette smoking and uranium mining were both associated with the prevalence of these atypias, and with carcinoma in situ and invasive cancer. Neither of these agents, however, appeared to be strongly associated with the duration of the stages of atypia. Age at start of uranium mining was more strongly associated with age at development of carcinoma in situ than other factors tested. There appears to be an average period of 4 or 5 years during which individuals exfoliate cells that are markedly atypical or represent carcinoma in situ in their sputum before developing invasive carcinoma of epidermoid or small cell, undifferentiated varieties. Periodic sputum surveillance of groups at elevated risk of bronchogenic cancer can utilize this period for early detection and treatment.

A mortality analysis of a group of white and Indian uranium miners was done by a life-table method. A significant excess of respiratory cancer among both whites and Indians was found. Nonmalignant respiratory disease deaths among the whites are approaching cancer in importance as a cause of death, probably as a result of diffuse parenchymal radiation damage. Exposure-response curves for nonsmokers are linear for both respiratory cancer and "other respiratory disease." Cigaret smoking elevates and distorts that curve. Light cigaret smokers appear to be most vulnerable to lung parenchymal damage. The predominant histologic cancer among nonsmokers is small-cell undifferntiated, just as it is among cigaret smokers.

THE identification of etiologic agents in chronic-disease epidemiology depends on sound study design, rigorous analytical methods and definitive criteria for evaluation. Unfortunately, the implementation of these principles has been all too infrequent in the field of occupational carcinogenesis. It is not surprising, therefore, that occupational studies on the same suspect carcinogen have often resulted in conflicting conclusions.A case in point is the lack of unanimity concerning the role of airborne radiation as an occupational carcinogen in man. This controversy dates from 1879, when Härting and Hesse1 first made note of the strikingly high percentage of deaths from pulmonary neoplasia . . .

Excess respiratory cancer has been demonstrated among all groups of uranium miners who have had more than 120 Working Level Months of radon daughter exposure. Lung cancer incidence rose with increasing exposure. Factors which might distort the exposure-response relationship were reviewed. Exposure to other agents such as cigarettes probably contributed to the excess, but these factors should not be considered in setting permissible levels. Respiratory cancers are continuing to appear at a high rate among the Study Group even though radon daughter levels have been markedly reduced and most of the Study Group have stopped mining.