J.L. Eccles

Vitamin A and cancer prevention II: Comparison of the effects of retinol and β-carotene

Former blue asbestos workers known to be at high risk of asbestos‐related diseases, particularly malignant mesothelioma and lung cancer, were enrolled in a chemo‐prevention program using vitamin A. Our aims were to compare rates of disease and death in subjects randomly assigned to β‐carotene or retinol. Subjects were assigned randomly to take 30 mg/day β‐carotene (512 subjects) or 25,000 IU/day retinol (512 subjects) and followed up through death and cancer registries from the start of the study in June 1990 till May 1995. Comparison between groups was by Cox regression in both intention‐to‐treat analyses and efficacy analyses based on treatment actually taken. Median follow‐up time was 232 weeks. Four cases of lung cancer and 3 cases of mesothelioma were observed in subjects randomised to retinol and 6 cases of lung cancer and 12 cases of mesothelioma in subjects randomised to β‐carotene. The relative rate of mesothelioma (the most common single cause of death in our study) for those on retinol compared with those on β‐carotene was 0.24 (95% CI 0.07–0.86). In the retinol group, there was also a significantly lower rate for death from all causes but a higher rate of ischaemic heart disease mortality. Similar results were found with efficacy analyses. Our results confirm other findings of a lack of any benefit from administration of large doses of synthetic β‐carotene. The finding of significantly lower rates of mesothelioma among subjects assigned to retinol requires further investigation. Int. J. Cancer 75:362–367, 1998.

Vitamin A and cancer prevention I: Observations in workers previously exposed to asbestos at Wittenoom, Western Australia

Our aim was to describe a vitamin A‐based cancer prevention program for former asbestos workers and to check for possible harmful effects by comparing rates of disease and death in study subjects with subjects who chose not to join. All subjects had been occupationally exposed to crocidolite at Wittenoom Gorge between 1943 and 1966; 1,677 subjects indicated interest in the program and 1,203 joined between June 1990 and May 1995. Comparison subjects consisted of 996 former workers known to be alive in Western Australia in 1990 who did not join the program. Program subjects were provided with annual supplies of vitamin A (either synthetic β‐carotene or retinol), help in quitting smoking and dietary advice. The comparison group received only mail contact. Both groups were followed up to December 1994 for vital status and cancer information, and rates of cancer and death from various causes were compared. Mortality in both groups was higher than expected (standardised mortality ratio 1.23 in program subjects and 1.67 in comparison subjects). After adjustment for age, smoking and asbestos exposure, the relative rates in participants compared with non‐participants was below 1 for all examined cancers and causes of death. For mesothelioma and lung cancer, group differences increased with time from entry, whereas other differences dissipated with time. No significant side effects were reported. In conclusion, program participants had significantly lower mortality than non‐participants, but the rates of the 2 groups converged with time. Int. J. Cancer 75:355–361, 1998.

Exposure to crocidolite and the incidence of different histological types of lung cancer.

OBJECTIVES: To estimate the relations between exposure to both tobacco smoke and crocidolite and the incidence of various histological types of lung cancer. METHODS: In 1979 all former workers from the Wittenoom asbestos industry who could be traced were sent a questionnaire on smoking history. Of 2928 questionnaires sent, satisfactory replies were received from 2400 men and 149 women. Of the men, 80% had smoked at some time and 50% still smoked. Occupational exposure to crocidolite was known from employment records and follow up was maintained through death and cancer registries in Australia with histological diagnoses obtained from the relevant State Cancer Registry. Conditional logistic regression was used to estimate the effects of tobacco and asbestos exposure on incidence of different cell types of lung cancer in a nested case-control design. RESULTS: Between 1979 and 1990, 71 cases of lung cancer occurred among men in this cohort: 27% squamous cell carcinoma, 31% adenocarcinoma, 18% small cell carcinoma, 11% large cell carcinoma, and 13% unclassified or indeterminate. Two of the classified cases and one unclassified case had never smoked. The incidence of both squamous and adenocarcinoma types of lung cancer were greatest in ex-smokers and in those subjects with the highest levels of exposure to crocidolite. After adjustment for smoking habit, the increase in incidence of lung cancer with increasing exposure to crocidolite was greater for squamous cell carcinoma than for adenocarcinoma. CONCLUSIONS: The results from this study have shown significant exposure-response effects for exposure to crocidolite, and both adenocarcinoma and squamous cell carcinoma of the lung. They also provide some further evidence against the theory that parenchymal fibrosis induced by asbestos is a necessary precursor to asbestos induced lung cancer.

Environmental exposure to crocidolite and mesotheliom: Exposure-response relationships

This study aimed to estimate exposure-response relationships for mesothelioma and environmental exposure to crocidolite. All 4,659 former residents of Wittenoom, Western Australia (WA) who lived there between 1943 and 1993 for at least 1 mo and were not directly employed in the crocidolite industry, were followed-up through the WA death, cancer and mesothelioma registries, electoral rolls, and telephone books. In 1992, all subjects who should be traced were sent a questionnaire. Exposure levels were estimated from results of periodic environmental surveys and duration of residence. Incidence rates were standardized to the World Population and Cox Regression was used to estimate the effects of exposure on incidence. To the end of 1993, 27 cases of mesothelioma were diagnosed. Mesothelioma cases stayed longer at Wittenoom, had a higher average intensity of exposure, and a higher cumulative exposure to crocidolite than control subjects. The standardized incidence of mesothelioma was 260 per million person-years, and was similar for males and females. The rate increased significantly with time from first exposure, duration of exposure and cumulative exposure. At these levels of crocidolite exposure, there is a significantly increased risk of mesothelioma, which is dose-dependent.