Faculty Bibliography

A cohort study is under way in New York City to evaluate how levels of endogenous reproductive hormones influence the risk of breast cancer. The study, in which approximately 15,000 women are being recruited, utilizes a prospective design in which volunteers are asked to provide repeated specimens of serum during the period 1985-1992. A case-control study nested within the cohort is planned by which specimens from all cases arising in the population and from a randomly selected sample of time-matched controls will be analyzed and compared. As of December 31, 1989, 13,609 volunteers had donated blood specimens, about 50% of whom had already donated more than once. Of the 187 incident breast cancer cases who are expected to arise in the cohort before the end of 1992, 77 have been detected thus far

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

It is well established that exposure to ionizing radiation during or after puberty increases a woman's risk for breast cancer, but it is less clear whether exposure to ionizing radiation very early in life is also carcinogenic. We studied the incidence of breast cancer prospectively in a cohort of 1201 women who received x-ray treatment in infancy for an enlarged thymus gland and in their 2469 nonirradiated sisters. After an average of 36 years of follow-up, there were 22 breast cancers in the irradiated group and 12 among their sisters, yielding an adjusted rate ratio of 3.6 (95 percent confidence interval, 1.8 to 7.3). The estimated mean absorbed dose of radiation to the breast was 0.69 Gy. The first breast cancer was diagnosed 28 years after irradiation. The dose-response relation was linear (P less than 0.0001), with a relative risk of 3.48 for 1 Gy of radiation (95 percent confidence interval, 2.1 to 6.2) and an additive excess risk of 5.7 per 10(4) person-years per gray (95 percent confidence interval, 2.9 to 9.5). We conclude that exposure of the female breast to ionizing radiation in infancy increases the risk of breast cancer later in life

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