The future of population monitoring in cancer research.
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Biomarkers, Tumor↗
Biomedical subjects
E Cardis
Publications and source records attributed to E Cardis.
Epidemiology of accidental radiation exposures.
Much of the information on the health effects of radiation exposure available to date comes from long-term studies of the atomic bombings in Hiroshima and Nagasaki. Accidental exposures, such as those resulting from the Chernobyl and Kyshtym accidents, have as yet provided little information concerning health effects of ionizing radiation. This paper will present the current state of our knowledge concerning radiation effects, review major large-scale accidental radiation exposures, and discuss information that could be obtained from studies of accidental exposures and the types of studies that are needed.
Dose-Response Relationship, Radiation↗
Effects of low doses and low dose rates of external ionizing radiation: cancer mortality among nuclear industry workers in three countries.
Studies of the mortality among nuclear industry workforces have been carried out, and nationally combined analyses performed, in the U.S., the UK and Canada. This paper presents the results of internationally combined analyses of mortality data on 95,673 workers (85.4% men) monitored for external exposure to ionizing radiation and employed for 6 months or longer in the nuclear industry of one of the three countries. These analyses were undertaken to obtain a more precise direct assessment of the carcinogenic effects of protracted low-level exposure to external, predominantly gamma, radiation. The combination of the data from the various studies increases the power to study associations between radiation and specific cancers. The combined analyses covered a total of 2,124,526 person-years (PY) at risk and 15,825 deaths, 3,976 of which were due to cancer. There was no evidence of an association between radiation dose and mortality from all causes or from all cancers. Mortality from leukemia, excluding chronic lymphocytic leukemia (CLL)--the cause of death most strongly and consistently related to radiation dose in studies of atomic bomb survivors and other populations exposed at high dose rates--was significantly associated with cumulative external radiation dose (one-sided P value = 0.046; 119 deaths). Among the 31 other specific types of cancer studied, a significant association was observed only for multiple myeloma (one-sided P value = 0.037; 44 deaths), and this was attributable primarily to the associations reported previously between this disease and radiation dose in the Hanford (U.S.) and Sellafield (UK) cohorts. The excess relative risk (ERR) estimates for all cancers excluding leukemia, and leukemia excluding CLL, the two main groupings of causes of death for which risk estimates have been derived from studies of atomic bomb survivors, were -0.07 per Sv [90% confidence interval (CI): -0.4, 0.3] and 2.18 per Sv (90% CI: 0.1, 5.7), respectively. These values correspond to a relative risk of 0.99 for all cancers excluding leukemia and 1.22 for leukemia excluding CLL for a cumulative protracted dose of 100 mSv compared to 0 mSv. These estimates, which did not differ significantly across cohorts or between men and women, are the most comprehensive and precise direct estimates of cancer risk associated with low-dose protracted exposures obtained to date. Although they are lower than the linear estimates obtained from studies of atomic bomb survivors, they are compatible with a range of possibilities, from a reduction of risk at low doses, to risks twice those on which current radiation protection recommendations are based.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Bladder cancer and occupational exposures.
OBJECTIVES: A hospital-based case-referent study was carried out in Lyon with the purpose of generating hypotheses about the role of occupational exposures to 320 compounds in bladder carcinogenesis. METHODS: Job histories were obtained by questionnaire for 116 cases and 232 reference patients with diseases other than cancer (one referent from the same hospital ward and one from another ward of the same hospital per case); the referents were matched for gender, hospital, age, and nationality. Systematic coding of exposures, with a blind analysis of job histories, was carried out by a team of experts in chemistry and occupational health. RESULTS: Significantly elevated odds ratios were observed for exposure to pyrolysis and combustion products [odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.0-4.0] when the general referents were used and for cutting fluids (OR 2.6, 95% CI 1.2-5.4) when tobacco consumption was adjusted for. The latter was highest among the category consisting of blue-collar and unskilled workers, supervisors, and agricultural workers (OR 4.6 95% CI 2.0-10.6), while the odds ratio for the other category was 0.8 (95% CI 0.3-2.7). An elevated odds ratio for exposure to inks was observed for the women (OR 14.0, 95% CI 1.8-106.5) on the basis of 14 exposed cases, but confounding factors could have been responsible for this result. Odds ratios for several other exposures (rubber: OR 5.7, nitrates: OR 8.2, coke dust: OR 3.5, meat additives: OR 3.8) were also elevated, but not significantly so when based on a small number of exposed cases. CONCLUSION: The observations of this investigation should be tested in future studies, in particular since exposures to agents such as cutting fluids or pyrolysis products are ubiquitous in industrial settings and may present an important public health hazard.
Adult↗
Estimating human cancer risk from the results of animal experiments: relationship between mechanism and dose-rate and dose.
Experimental animals are often used as surrogate models in estimating human cancer risk from environmental agents when adequate epidemiological data are not available. Studies in experimental animals have usually evaluated the effects of exposure to single substances; however, humans receive combinations of exposures, to both initiators and promoters of carcinogenesis. Exposure to several agents may modify the carcinogenic process of one of them. For many agents, the relationship between dose and carcinogenic response depends on both dose-rate and cumulative dose. For a given total dose, dose-rate may affect carcinogenic potency both qualitatively (target organ) and quantitatively. The effects of dose-rate are a function of total dose, species, and most importantly, the mechanism by which the agent exerts its carcinogenic effect. Prediction of the effects of different dose-rates of potentially carcinogenic agents can be based on knowledge of its mechanism of action.
Animals↗
Childhood leukaemia following the Chernobyl accident: the European Childhood Leukaemia-Lymphoma Incidence Study (ECLIS).
The objective of the European Childhood Leukaemia-Lymphoma Incidence Study (ECLIS) is to investigate trends in incidence rates of childhood leukaemia and lymphoma in Europe, in relation to the exposure to radiation which resulted from the accident at the Chernobyl nuclear power plant in April 1986. In this first report, the incidence of leukaemia in children aged 0-14 is presented from cancer registries in 20 European countries for the period 1980-1988. Risk of leukaemia in 1987-1988 (8-32 months post-accident) relative to that before 1986, is compared with estimated average dose of radiation received by the population in 30 geographic areas. The observed changes in incidence do not relate to exposure. The period of follow-up is so far rather brief, and the study is planned to continue for at least 10 years.
Accidents↗
Epidemiological designs in radioepidemiological research.
Most of the information currently available on radiation effects comes from the observation of individuals who received high doses, either from one acute exposure or a series of exposures. Because of the uncertainties in extrapolating risks from these studies to the exposure circumstances of most cancers today (in particular, low-level environmental exposure), direct epidemiologic studies of populations receiving low doses chronically are needed. The effects which we want to quantify are likely to be small, however, and extreme care must therefore be put into the design of such studies if they are to be informative for risk assessment purposes. The areas of particular importance in designing risk assessment studies are reviewed. The advantages and limitations of various epidemiological study designs, and the problems and importance of dosimetry are discussed. Examples from the recent epidemiological literature are presented to illustrate the discussion.
Case-Control Studies↗
Black tobacco and cancer: introducing an epidemiological review.
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Europe↗
Cancer risks related to electricity production.
The International Agency for Research on Cancer has previously evaluated the cancer risks associated with fossil fuel-based industrial processes such as coal gastification and coke production, substances and mixtures such as coal tars, coal tar pitch and mineral oils, and a number of substances emitted from fossil-fuelled plants such as benzo[a]pyrene and other polycyclic aromatic hydrocarbons, arsenic, beryllium, cadmium, chromium, nickel, lead and formaldehyde. Based on these evaluations and other evidence from the literature, the carcinogenic risks to the general population and occupational groups from the fossil fuel cycle, the nuclear fuel cycle and renewable cycles are reviewed. Cancer risks from waste disposal, accidents and misuses, and electricity distribution are also considered. No cycle appears to be totally free from cancer risk, but the quantification of the effects of such exposures (in particular of those involving potential exposure to large amounts of carcinogens, such as coal, oil and nuclear) requires the application of methods which are subject to considerable margins of error. Uncertainties due to inadequate data and unconfirmed assumptions are discussed. Cancer risks related to the operation of renewable energy sources are negligible, although there may be some risks from construction of such installations. The elements of knowledge at our disposal do not encourage any attempt toward a quantitative comparative risk assessment. However, even in the absence of an accurate quantification of risk, qualitative indication of carcinogenic hazards should lead to preventive measures.
Accidents, Occupational↗
Cytochrome P-450 isozyme pattern is related to individual susceptibility to diethylnitrosamine-induced liver cancer in rats.
Differences in susceptibility to chemical carcinogenesis between rodent strains and species have been linked to variations in genetically-determined mixed function oxidase activities. In order to verify whether such variations also determine the susceptibility of individual animals of the same strain to a chemical carcinogen, outbred male Wistar rats were administered diethylnitrosamine (DEN) (1, 2, or 3 mg/kg) five times a week for 20 weeks. The relationship was examined between the outcome (i.e., presence or absence of liver tumors, and latency period) and the hepatic activities of mixed function oxidases and conjugating enzymes, as well as of O6-methylguanine-DNA-methyltransferase, measured before the carcinogen treatment. In addition, the metabolic profiles of two model drugs, antipyrine and disopyramide, in the urine were analyzed and correlated with the carcinogen susceptibility. The length of the latency period of hepatocellular tumors in individual rats was negatively related to the activities of hepatic dimethylnitrosamine N-demethylase, aryl hydrocarbon hydroxylase and epoxide hydrolase and positively related to the amount of microsomal protein. Consistent relationships between the other 10 measured parameters and the susceptibility to DEN-induced carcinogenesis were not detected. Long-term treatment with DEN slightly decreased the proportion of metabolism of antipyrine into norantipyrine, and increased the share of 4-hydroxyantipyrine; a decrease in the metabolism of disopyramide to N-deisopropyldisopyramide was also detected. It is concluded that the pattern of cytochrome P-450 isoenzymes is related to differences in individual susceptibility to nitrosamine-induced carcinogenesis. The relationship was most marked at low dose levels, which are the levels at which nitrosamine exposures of humans are known to occur.
7-Alkoxycoumarin O-Dealkylase↗
Cancer incidence correlations: genital, urinary and some tobacco-related cancers.
Bivariate correlations between sex-specific age-adjusted incidence rates of 10 genital and urinary tract cancer sites and lung cancer were calculated. The data base used was that published in the 5th edition of the series Cancer incidence in five continents. The purpose of the analyses was to test the consistency of the data with the hypothesis of a common risk factor for genital cancers and other cancers of the urinary tract and for lung and genital cancers. The results indicate that the incidence of cervical cancer is strongly correlated with that of cancer of the penis, of other cancers of the female genital tract and of chorioepithelioma. In countries at low/intermediate risk for cervical cancer (mostly developed Western countries), the incidence of cervical cancer is also correlated with that of lung cancer in males. The incidence of male lung cancer is, moreover, strongly correlated with cancers of the prostate, penis, testis, bladder and other urinary tract cancers. These analyses support the views that: urogenital cancers in both sexes might share (a) common risk factor(s), which may be certain types of human papilloma-virus; and that cigarette smoking is likely to be a risk factor for most of these cancers in countries where the use of tobacco has been widespread for a long time. Other suggestive etiological conclusions about less well-studied cancer sites are also presented.
Age Factors↗
Tumour incidence in the progeny of male rats exposed to ethylnitrosourea before mating.
BDVI male rats were given a single i.p. dose of 80 mg/kg b.w. ethylnitrosourea (ENU), and each rat was then mated at weeks 1, 2, 3, 4 and 5 after treatment with 3 untreated females. A decrease in the fecundity of the treated males was observed, particularly when they were mated 5 weeks after ENU treatment. The average litter size was lower in the treated group, especially for females mated in week 4. No significant differences in pre- or post-weaning mortality were noted between control and treated groups. A slight, non-significant increase in the incidence of brain tumours was observed in the progeny of treated males compared with the controls. The incidence of thyroid tumours was significantly higher in controls but this difference disappeared when adjustment was made for litter effect and intralitter dependence.
Animals↗
Systematic modulation by human diet levels of dietary fibre and beef on metabolism and disposition of benzo[a]pyrene in the gastrointestinal tract of Fischer F344 rats.
Groups of male Fischer F344 rats isocalorically consuming cooked, low-fat human diets were given magnetic polyethyleneimine (PEI) microcapsules and [14C]benzo[a]pyrene (B[a]P) by gavage in order to determine the effects of 3-fold changes in levels of dietary fibre non-starch polysaccharide (NSP) and beef protein during gastrointestinal transit on microcapsule trapping and associated parameters. Total 14C trapped by microcapsules during 70 h was decreased by fibre and increased by beef with significant effects (P = 0.03) for dietary mass ratio beef/fibre and compared to controls eating chow. Total B[a]P excreted in faeces and the ration for faeces/urine were increased by fibre and not by beef; the distribution of B[a]P metabolites between liquid and solids of faeces was increased by both factors but there was a net decrease by fibre when allowing for its influence on faecal mass. The distribution of binding between microcapsules and faecal solids was increased significantly by beef, but fibre had no effect when mass-normalized. B[a]P metabolites were extracted from microcapsules by methanol-ammonia and HPLC assay showed mainly benzo[a]pyrene-3,6-dione (B[a]P 3,6-dione), benzo[a]pyrene-1,6-dione (B[a]P 1,6-dione), an unidentified metabolite and substances consistent with tetraols; the beef (P = 0.02) and beef/fibre ratio (P = 0.01) significantly increased B[a]P-1,6-dione trapped and released. In vitro, B[a]P 3,6-semidione (dione reduced form) was bound by PEI microcapsules; the extent of extraction/hydrolysis was much lower than for B[a]P e,6-dione or B[a]P 7,8-diol 9.10-epoxide. Urinary excretion of B[a]P metabolites was decreased by fibre but not by beef. Nearly all the above parameters were different in a control group consuming rat chow. Taken together, these results are consistent with the following conclusions; (i) dietary fibre NSP overall decreases the availability of B[a]P metabolites to contact microcapsules and intestinal mucosa through static bulking rather than absorption; (ii) beef protein increases binding to microcapsules, and enhances free radical activation of B[a]P to its 6-yl radical form; (iii) a systematic set of concordant relationships for B[a]P disposition were found between faecal solids, faecal liquids, microcapsules and urine; and (iv) rat chow produced effects quite unrepresentative of the range for human diets prepared to be in the norm for human use. Endogenous UV-absorbing substances trapped by microcapsules or excreted in urine were also altered by dietary beef levels and were different from those of chow-consuming animals. It is generally concluded that human diets can and should be used in studying carcinogen metabolism and disposition.
Animals↗
Mortality of a cohort in a polyamide-polyester factory in Lyon: a further follow up.
In 1981-2 a retrospective study was undertaken in a polyamide-polyester factory in Lyon, France, to evaluate the effect of exposure to phthalates, nickel catalysers, and other chemicals in the work environment. The present paper reports the results of the follow up of this cohort up to July 1986. A slightly increased risk of cancers, in particular of the lung (44 cases), marginally related to exposure category but not significantly related to duration of exposure was found. The excess of skin cancers noted previously has disappeared, whereas an excess of cases of bladder cancer (based on seven cases) may be noted, mainly among nylon workers. The cohort is still young, however, and a continued follow up is likely to yield important information about the potential hazards associated with the nylon and tergal polymer industry.
Chemical Industry↗
Review of experiments on multigeneration carcinogenicity: of design, experimental models and analyses.
It is widely accepted that parental exposure to a carcinogen may result in an increased risk for cancer in otherwise untreated offspring. Results of a new experiment and a review of published studies on multigeneration carcinogenesis are presented and discussed on the basis of the animal model used and of the design and analysis of the individual experiments. Several of the studies indicate an effect of multigenerational carcinogenesis, characterized by one or more of the following: an increase in tumour incidence (either specific to the carcinogen used or spontaneous, or neither spontaneous nor specific); an increase in tumour multiplicity; or transmission of the initiated state through germ cells. In several other well-conducted experiments, either no multigeneration effect was observed or the results were ambiguous. The clearest, most consistent results are obtained in experiments on mice. The published results, however, cannot preclude the possibility that the observed increases are due to a genetic predisposition rather than to induction of an oncogenic mutation in the germ cells. The studies reviewed here indicate that mothers and fathers may differ in transmission efficiency, but it would be premature to draw definitive conclusions. More work is needed in this field, but it appears that mice may be a more sensitive animal model for the study of multigeneration carcinogenesis experiments than rats. In future studies of this effect, experimental designs which allow for assessment of the relative efficiency of transmission through the mother and the father should be implemented. Care should also be taken to plan experiments that are large enough, and to retain all pertinent information, in particular litter information, in order that clear conclusions can be drawn from the results.
Animals↗
Degree of confounding bias related to smoking, ethnic group, and socioeconomic status in estimates of the associations between occupation and cancer.
In occupational cancer epidemiology, many studies are carried out without access to information on smoking and other potential confounding variables. It is unclear whether such deficiencies are likely to cause serious bias in estimates of cancer-occupation associations. An empiric investigation was carried out to determine the effect of inclusion or exclusion of three variables--smoking, ethnic group, and socioeconomic status--on estimates of odds ratios (OR) between 25 occupations and three types of cancer--lung, bladder, and stomach. Of the 75 associations studied, only one OR was distorted by more than 40% when comparing unadjusted with adjusted estimates; three were distorted by between 30% and 40%; four others by between 20% and 30%. Of the eight associations which were distorted by more than 20%, seven involved lung cancer and one involved bladder cancer; none involved stomach cancer. An additional analysis was carried out on the 25 lung cancer-occupation associations to determine whether the nature of the stratification on smoking (ie, whether crude or "precise" categories were used) gave different OR estimates. The differences in ORs induced by different parametrizations of the smoking variable were relatively small. Our results support the view that relative risks between lung cancer and occupation in excess of 1.4 are unlikely to be artifacts due to uncontrolled confounding. For bladder and stomach cancer, the corresponding cut point may be as low as 1.2. In studies of occupation and cancer, uncontrolled confounding due to smoking and social class may not be as serious a threat to the integrity of results as is sometimes feared.
Adult↗
[Transzygotic carcinogenic effect of nitrosoethylurea in rats].
The results of two experiments on the transzygotic transfer of the nitrosoethylurea (NEU) carcinogenic effect are presented. In the first experiment female rats received 60 mg/kg b. w. of NEU at 16, 18 and 20th day of the pregnancy. Their F1 descendants developed multiple tumours of the nervous system after a short latency (up to 40 weeks). The rats of F2, F3, F4 and F5 generations which were not in a direct contact with NEU developed a statistically higher incidence of tumours occurring spontaneously (those of mammary gland, pituitary, and haematopoietic tissue). However, the incidence of nervous system tumours was at the level of controls. In the second experiment male rats received 80 mg/kg b. w. of NEU and then were mated with untreated females. The incidence of the nervous system tumours in the descendants of treated males was somewhat higher than in the controls. The manifestations and mechanisms of the transzygotic effect are discussed.
Animals↗
Mortality experience in a polyamide-polyester factory.
Chemical workers have become increasingly concerned about the presence of carcinogens in their occupational environment. As a result, a number of studies of excess cancer mortality have been undertaken in groups of workers with well-characterized exposures. This paper reports the results of one such study carried out in a polyamide-polyester factory in France. A retrospective cohort design was chosen to evaluate the effect of exposure to phthalates, nickel catalyzers, and other chemicals in the work environment. Only a slight excess of cancers, marginally related to exposure category yet not significantly related to length of exposure, was found. The cohort, however, was young but stable, and a continued follow-up is therefore both feasible and justifiable, since it is likely to yield important information about the potential hazards associated with the tergal polymer industry.
Chemical Industry↗