Faculty Bibliography

Traditional treatment for testicular seminoma produces excellent survival. We report five, second non-testicular malignancies which occurred in a group of seminoma patients. A total of 79 men with primary testicular seminoma were available for analysis. All underwent a radical inguinal orchiectomy. Those with Stage I disease received adjuvant radiation therapy to the para-aortic and ipsilateral iliac nodes. The usual dose was 2500 cGy in 15 treatments. Stage II patients also received prophylactic mediastinal radiation therapy to a dose of 2500 cGy. None of the 51 Stage II patients died of tumour, whereas four of the 28 Stage II patients died of their disease. The median follow-up was ten years (range 4-25 years). The second malignancies seen were melanoma (2), myeloma, caecal adenocarcinoma, and retroperitoneal fibrosarcoma. All but one tumour developed within the radiation fields. Based on US SEER data for white males, only 1.5 cancers were expected, giving significantly greater (P = 0.04) relative risk. This observation lends support to observation, rather than elective treatment, in patients with Stage I testicular cancer

At least 350,000 workers at U.S. radiation facilities are being followed up to monitor their mortality experience, with particular reference to cancer. Although these studies are expensive, they are needed from the standpoint of public health and radiation protection; they also provide a useful check that the risk extrapolation models based on high dose data are not seriously out of line. Unfortunately, there are a number of problems in interpreting radiation worker studies that stem mainly from the fact that the expected magnitude of effects is small because of the low doses. Problems of falsely positive effects caused by chance or by study biases are difficult to distinguish from real effects. Dose-effect analyses and pooled analyses from several studies offer some improvements in assessing the risk from low doses but do not obviate all the problems. Future studies should explore whether there are biological markers of exposure, damage, or susceptibility that would improve our power to assess individual risk

A retrospective cohort study was conducted to examine the mortality experience of 2174 men employed between 1940 and 1978 by a large chemical company and who had been assigned to a chemical production department that used or produced ethylene oxide (EO). Comparisons were made with the general United States population, the regional population, and with a group of 26,965 unexposed men from the same plants. Comparisons with general United States death rates showed fewer deaths than expected in the EO group due to all causes and for total cancers. There was no statistically significant excess of deaths due to any cause. Seven deaths each due to leukaemia and pancreatic cancer were observed with 3.0 and 4.1 deaths expected. Among the subcohort of men who worked where both average and peak exposure levels were probably highest, however, one death due to pancreatic cancer (0.9 expected) and no deaths due to leukaemia were observed. Four of the seven who died from leukaemia and six of the seven who died from pancreatic cancer had been assigned to the chlorohydrin department where the potential for exposure to EO is judged to have been low. The relative risk of death due to each disease was strongly related to duration of assignments to that department. When men who worked in the chlorohydrin department were excluded, there was no evidence for an association of exposure to EO with pancreatic cancer or leukaemia. Together with the failure to show independent EO associations, the chlorohydrin department results suggest that leukaemia and pancreatic cancer may have been associated primarily with production of ethylene chlorohydrin or propylene chlorohydrin, or both. These results emphasise the importance of examining additional concurrent/asynchronous exposures among human populations exposed to EO

There are about a dozen studies of the incidence of skin cancer among irradiated populations with known skin doses that are available for estimating the risk of radiation-induced skin cancer. It is of note that they provide no evidence for a dose threshold and are compatible with a linear dose-response relationship, at least for ultraviolet radiation exposed skin. The studies also provide varying amounts of evidence concerning a number of other important issues in assessing skin cancer risk: types of skin cancer induced by ionizing radiation, the appropriateness of relative risk vs absolute risk models, combined effects of ionizing and UV radiations, and variations in sensitivity to skin cancer induction among demographic and genetic subgroups. Little epidemiological information is available on several factors, such as the RBE for high-LET radiation, the effects of dose protraction or fractionation, or variations in risk by age at irradiation. A reasonable estimate of skin cancer lethality was 0.2 per cent when weighted for the relative proportions of squamous cell and basal cell skin cancers. Average risk estimates of radiation-induced skin cancer incidence were: absolute risk (AR) of 8.5 X 10(-4) person-year-Sv and excess relative risk (RR) of 52 per cent/Sv. Lifetime skin cancer risk was calculated by life-table methods for males from exposures spread out over ages 20-60 years. The estimates for excess skin cancer incidence were 2 per cent and 11 per cent per Sv under the AR and RR models, respectively, while the corresponding mortality risks were 4 X 10(-5) and 2 X 10(-4) per Sv

The literature is briefly summarized as to how several nutrients affect immune function, susceptibility to infection, and cancer susceptibility or progression. Nutritional deficiencies can impair immunity and so influence susceptibility to infectious agents, including ones that are common and relatively virulent in acquired immune deficiency syndrome (AIDS) patients. A variety of nutrients affect several of the immune functions that are defective in human immunodeficiency virus (HIV)-infected individuals. For example, beta-carotene increased the number of CD4+ cells; vitamin E decreased the number of CD8+ cells and increased the CD4+/CD8+ ratio; vitamin D decreased the CD4+/CD8+ ratio; and iron increased the number of peripheral lymphocytes in humans receiving supplementation. Furthermore, nutritional deficiencies can influence gastrointestinal function, while infectious diseases can influence nutrient requirements by altering the efficiency of absorption and the rate of tissue metabolism. Malnutrition, depressed serum zinc levels, and intestinal nutrient malabsorption have been found in AIDS patients. The above findings suggest that dietary manipulations might diminish the immune defects in HIV infection and enhance resistance to opportunistic infections. However, dietary alterations in immune defects are generally not well quantified and may be small relative to the magnitude of the defects observed in AIDS patients. Because conflicting or adverse effects have been reported for some nutrients, recommendations for dietary supplementation in HIV-infected individuals are premature and possibly hazardous. Further studies are much needed to relate dietary nutrient intakes to clinical outcomes

Over the last 40 years the amount of knowledge about human radiation effects has increased dramatically. During that interval, radiation epidemiologists have documented a number of additional types of radiation-induced cancer and have established rough estimates of the magnitude of cancer risks. Nevertheless, we currently have inadequate knowledge about a number of factors that help define the magnitude of radiation risks. These include questions of estimating risk over the lifetime, shapes of dose-effect curves, magnitude of risks at low doses, potentiation between radiation and other agents, and the nature and role of host susceptibility factors. Data from various studies are used to illustrate these questions