Altered glycosylation of proteins in cancer: what is the potential for new anti-tumour strategies.

It is becoming increasingly apparent that cell surface oligosaccharides play pivotal roles as recognition molecules in a range of cell communication and adhesion processes. Alterations in cellular glycosylation are also associated with diseases, including cancer, and may have functional significance. This paper gives an overview of the complex topic of cellular glycosylation mechanisms and reviews the well-documented alterations in cellular glycosylation of proteins in malignancy. One particular type of cancer-associated glycosylation change, the incomplete synthesis of O-linked glycans, is highlighted, and its possible functional significance in cancer cell metastatic mechanisms is discussed. The significance that cancer-associated changes in glycoprotein glycosylation may have in new approaches to anti-tumour therapies is explored.

Studies of U.S. radium dial workers: an epidemiological classic.

The tragic history of the exposure during the second and third decades of this century in the United States of radium dial workers, patients and members of the public to ionizing radiation from internally deposited isotopes of radium is well documented. Recognition of abnormal health outcomes among female dial workers and determination of a causal association between these outcomes among the workers and their exposure to radium leading to the development of protection standards is a classic example of an epidemiological process whereby knowledge and understanding of "the distribution and determinants of disease" evolve. Health effects studies involving U.S. female dial workers began in the early 1920s and continued into the present decade. These studies are discussed in the context of the epidemiological process whereby cause-effect relationships may be postulated, evaluated and refined to the benefit of workers and the general public.

Methods for analyzing combined data from studies of workers exposed to low doses of radiation.

Epidemiologic studies of workers exposed occupationally to protracted low doses of radiation provide a direct assessment of health effects resulting from such exposure and thus supplement information provided by studies of populations exposed at high doses of radiation and high dose rates. Analyses based on combined data from several studies can be expected to provide a more thorough assessment of low dose occupational studies and more precise risk estimates than can be obtained from any single study. Statistical methods for conducting such combined analyses are discussed, and different approaches, such as basing analyses on various levels of aggregation of exposure data, are compared and evaluated. Emphasis is given to methods for obtaining risk estimates and confidence limits that can be appropriately compared with estimates that form the basis for current radiation protection standards; these estimates have been obtained through extrapolation from high dose data. Methods are illustrated using combined data on workers at three US Department of Energy facilities: the Hanford Site, Richland, Washington; the Oak Ridge National Laboratory, Oak Ridge, Tennessee; and the Rocky Flats Nuclear Weapons Plant, Denver, Colorado.

Health effects of ionizing radiation.

Although humans have evolved in an environment of ionizing radiation, it was not until man-made sources were developed that the effects of ionizing radiation started to become known. Detection and measurement of radiation is not only sophisticated but widely applied. This article deals with exposure to this kind of radiation and the risk it may cause.

Analyses of combined mortality data on workers at the Hanford Site, Oak Ridge National Laboratory, and Rocky Flats Nuclear Weapons Plant.

An important objective of studies of workers exposed occupationally to chronic low doses of ionizing radiation is to provide a direct assessment of health risks resulting from this exposure. This objective is most effectively accomplished by conducting combined analyses that allow evaluation of the totality of evidence from all study populations. In this paper, combined analyses of mortality in workers at the Hanford Site, Oak Ridge National Laboratory, and Rocky Flats Nuclear Weapons Plant are presented. These combined analyses provide no evidence of a correlation between radiation exposure and mortality from all cancer or from leukemia. Of 11 other specific types of cancer analyzed, multiple myeloma was the only cancer found to exhibit a statistically significant correlation with radiation exposure. Estimates of the excess risk of all cancer and of leukemia, based on the combined data, were negative. Upper confidence limits based on the combined data were lower than for any single population, and were similar to estimates obtained from recent analyses of A-bomb survivor data. These results strengthen support for the conclusion that estimates obtained through extrapolation from high-dose data do not seriously underestimate risks of low-dose exposure, but leave open the possibility that extrapolation may overestimate risks.

Chemical exposures and central nervous system cancers: a case-control study among workers at two nuclear facilities.

In a nested case-control study of workers employed between 1943 and 1977 at two nuclear facilities, we evaluated the possible association of primary CNS cancers with occupational exposure to chemicals. Seventy-two white male and 17 white female workers who, according to the information on death certificates, died of primary CNS cancers were identified as cases. For each case, four controls were matched on race, sex, facility at which initially employed (cohort), year of birth, and year of hire. Each job title/department combination was subjectively evaluated for potential exposure to each of 26 chemicals or chemical groups. Statistically significant associations were not found between CNS cancer deaths and any of the 26 chemicals. An increased risk of CNS cancer occurrence was observed among subjects employed for more than 20 yr (OR = 7.0, 95% CI = 1.2,41.1, cases = 9).

Brain cancer and nonoccupational risk factors: a case-control study among workers at two nuclear facilities.

In a nested case-control study of nuclear workers, 82 brain cancer cases were compared with 328 matched controls to investigate the possible association with nonoccupational risk factors such as histories of epilepsy or head injury. We observed a moderately strong association between brain cancer occurrence and history of epilepsy (OR = 5.7, 95 per cent CI: 1.0, 32.1), but did not find a positive association with previous head injury (OR = 0.9, 95 per cent CI: 0.2, 4.2).

CNS cancers and radiation exposure: a case-control study among workers at two nuclear facilities.

A nested case-control study was conducted among workers employed in two nuclear facilities to investigate the possible association of primary CNS cancers with occupational exposure to radiation from external and internal sources. External radiation monitoring data from film badges were available for 27 cases and 90 matched controls. The radiation dose to the lung from internally deposited uranium was estimated for 47 cases and 120 matched controls from area and personnel monitoring data and was used in analyses in lieu of the brain dose. No association was observed between deaths from CNS cancers and exposure to ionizing radiation from external or internal sources. However, due to the small number of monitored subjects and low doses, a modest association could not be ruled out.

Radiation, work experience, and cause specific mortality among workers at an energy research laboratory.

A retrospective cohort mortality study was conducted among 8375 white male employees who had worked at the Oak Ridge National Laboratory for at least one month between 1943 and 1972. This plant has been the site of energy related research, including uranium and plutonium reactor technology and radioisotope production. Radiation doses, primarily from gamma rays, were generally low; the median cumulative exposure for workers was 0.16 rems. Historical follow up was conducted for the years 1943-77 and ascertainment of vital status was achieved for 92.3% of the cohort. Standardised mortality ratios (SMRs) were computed to contrast the subjects' cause specific mortality experience with that of the United States white male population. The observed number of 966 deaths from all causes was 73% of the number expected. Mortality deficits were also seen for arteriosclerotic heart disease (SMR = 0.75; 344 observed) and all cancers (SMR = 0.78; 194 observed). These results are indicative of the healthy worker effect and the favourable influence on health of the cohort's relatively high socioeconomic status. Non-statistically significant raised SMRs were seen for all leukaemias (SMR = 1.49, 16 observed), cancer of the prostate (SMR = 1.16, 14 observed), and Hodgkin's disease (SMR = 1.10, 5 observed). Internal comparisons of mortality (standardised rate ratios, SRRs) were made between subgroups of the cohort according to radiation dose level and duration of employment in various job categories. No consistent gradients of cause specific mortality were detected for radiation exposure. Leukaemia mortality was highest among workers with greater than or equal to 10 years employment in engineering (SRR = 2.40) and maintenance (SRR = 3.12) jobs. The association of leukaemia with employment in engineering was unexpected; maintenance jobs entail potential exposures to radiation and to a wide range of organic chemicals; metals, and other substances.

A mortality study of men exposed to elemental mercury.

A cohort of 2,133 white males who were exposed to elemental mercury vapors between 1953 and 1963 was followed up through the end of 1978. Death certificates were obtained for 371 of the 378 workers who were reported by the Social Security Administration to be deceased. The mortality experience of this group was compared with the age-adjusted mortality experience of the U.S. white male population. Mortality has not been studied previously in assessing the long-term health effects of mercury exposure. Standardized mortality ratios (SMRs) were calculated for a comparable unexposed worker population to determine the mortality patterns among workers at the same plant who were not involved in the mercury process. Statistically significant excesses of deaths from cancer of the lung (SMR = 1.34; 71 observed, 52.9 expected) and cancer of the brain and other CNS tissues (SMR = 2.30; 13 observed, 5.65 expected) were observed among the plant workers who were not involved in the mercury process. An excess of deaths from cancer of the lung was also observed among the mercury workers (SMR = 1.34; 42 observed, 31.36 expected), although the elevation of this SMR was not statistically significant. Since excesses of lung cancer were evident in both groups of workers, it is unlikely that they are related to the mercury exposure and more probable that they are due to some other factor present in the plant or to some life-style factor prevalent among the plant workers.(ABSTRACT TRUNCATED AT 250 WORDS)