Showing papers by "International Agency for Research on Cancer published in 1986"

Case‐control study on colorectal cancer and diet in marseilles

Abstract: A case-control study of cancer of the colon and rectum was conducted in the Marseilles region of southern France. Cases (399) and a corresponding number of controls, matched for age and sex, were included, the controls being selected from patients undergoing functional re-education for injuries or trauma which reduced their mobility. A dietary history questionnaire was used to determine the usual eating habits during the year preceding diagnosis for cases, or preceding interview for controls. The cases reported lower consumption of vegetables and oil than controls, but no differences were seen in the consumption of meat, bread, eggs or butter. The intake of several nutrients, particularly vitamins B2, B6, C, potassium, iron, magnesium and vegetable fibre, was lower among cases. However, when all these nutrients were analysed jointly and adjusted one for the other, only potassium retained a significant effect. This may be due to the high degree of colinearity between the estimated intake of many nutrients. No association was seen with fat or fibres from cereals.

Aflatoxin B1 binding to plasma albumin and liver DNA upon chronic administration to rats.

Abstract: The hepatocarcinogen aflatoxin B1 (AFB1) was administered to male Wistar rats by oral intubation in either single or repeated doses and the binding to plasma protein and liver DNA determined. Twenty-four hours after a single dose (3.5-200 micrograms/kg AFB1) a constant ratio was found between levels of aflatoxin bound to plasma protein and that bound to liver DNA. In total 0.98-2.15% of the administered dose was bound to the plasma protein at this time point. In the chronic study rats received two doses of 0.5 microgram AFB1/day and groups of animals were killed on days 2, 3, 7, 14, 21 and 24. Binding of aflatoxin to plasma protein accumulated to a level 3-fold higher than that seen after a single dose. Levels of binding reached a plateau between days 7 and 14 of treatment and then remained stable until the end of the experiment. Binding to DNA also accumulated, 2.5-fold and in parallel to plasma protein, binding reached a plateau between days 7 and 14 of treatment. In both the chronic and acute studies fractionation of the plasma proteins by Sephadex G-200 chromatography showed that all detectable bound aflatoxin was associated with a single peak corresponding to albumin. Thus, a constant ratio was observed, after chronic or single exposure, between the concentration of plasma albumin-bound aflatoxin and that bound to DNA of the liver, the target organ for carcinogenesis by AFB1. In order to investigate the proposed role of AFB1 in the aetiology of primary hepatocellular carcinoma in man it would be of great value to have a method for assessing long-term human exposure at an individual level. The relevance of the observations presented in this paper are discussed in the light of such a requirement.

A case‐control study of dietary factors and stomach cancer risk in Poland

Abstract: We report results from a case-control study on stomach cancer conducted in 1980-81 in Cracow, Poland, where the risk of this disease is among the highest reported world-wide. One hundred and ten cases from a surgical clinic were matched by age and sex to the same number of controls from the same hospital. A matched series from a population-based health survey was also considered. After adjusting for residency, smoking and various food items, cases and hospital controls showed significant differences in consumption of fruits (RR rarely vs. daily: 3.24; 95% CI: 1.56-6.77), joint consumption of vegetables, salads and fruits (RR low vs. high: 4.23; 95% CI: 1.41-12.63), and consumption of protein-containing foods (RR low vs. high: 0.23; 95% CI: 0.08-0.61). Consumption of strong alcoholic beverages on an empty stomach (before breakfast) was associated with an RR of 2.09 (1.04-4.22). The findings are discussed in relation to the apparent urban/rural difference in stomach cancer incidence in Poland and the possible underlying etiological factors involved.

Response of experimental animals to human carcinogens: an analysis based upon the IARC Monographs programme

Abstract: Only the results of epidemiological studies can be used to establish a causal relationship between an exposure to an agent and human cancer; however, such studies often cannot be carried out due to limitations of population or latent period or to the presence of mixed exposures. It is essential, therefore, that the validity be established of extrapolating to humans the results obtained from long-term carcinogenicity tests in animals. The responses of experimental animals to known and suspected human carcinogens, as evaluated in the IARC Monographs series, were analysed as an indication of the sensitivity of animal tests for predicting human carcinogens. Although the response was high - 84% - it would have been even higher had all the compounds been adequately tested experimentally. An additional finding was that for many exposures causally related to human cancer, there is a target organ in common between humans and at least one animal species, despite many inherent physiological differences. These findings show clearly the importance of experimental carcinogenicity studies in the primary prevention of cancer.

Epstein-Barr virus status and tumour cell phenotype in sporadic Burkitt's lymphoma

Abstract: Burkitt's lymphoma (BL) biopsy cells and derived cell lines can be grouped according to their patterns of reactivity with 6 selected monoclonal antibodies (MAbs) against B cell-associated surface antigens. Group I cells react only with MAbs J5 and 38.13, recognising the common acute lymphoblastic leukaemia antigen and a BL-associated antigen respectively; group II cells react with J5 and 38.13 and with one or more of a set of MAbs (Ki-24, MHM6, AC2, Ki-1) against "lymphoblastoid" antigens; group III cells react only with these anti-"lymphoblastoid" MAbs. Tumour biopsy cells from 17 cases of sporadic BL, 9 positive for the Epstein-Barr (EB) virus genome and 8 negative, have been analysed during the process of cell line establishment in vitro. In early passage the EB virus-negative BL cells showed either a group I phenotype or gave an additional reactivity with MAb Ki-24 which placed them in group II; these phenotypes remained essentially stable with continued growth of the cell lines for up to 50 passages. By contrast the EB virus-positive BL cells were much more susceptible to phenotypic change in vitro. Although such cells displayed a group I or group II phenotype in early passage, many of the lines soon moved into group III whilst retaining the karyotypic markers indicative of their malignant origin. These observations suggest that a resident EB virus genome can drive the in vitro progression of BL cells towards a more "lymphoblastoid" phenotype. This was confirmed in subsequent experiments where virus-negative BL cell lines were converted to EB virus positivity by in vitro infection. Clearly, therefore, phenotypic analysis of long-established lines can lead to false distinctions being drawn between the EB virus-positive and -negative forms of sporadic BL; both may derive from the same sub-population of target B cells in vivo.

The Copenhagen case-control study of bladder cancer. II. Effect of coffee and other beverages.

Abstract: During the years 1979-1981 a population-based case-control study of bladder cancer including papilloma was performed in greater Copenhagen. A total of 371 patients (280 males; 91 females), and a comparable age- and sex-stratified group of 771 controls (577 males; 194 females) remained for logistic regression analysis. Controls were selected at random from the general population of the study area. All persons were questioned about their drinking habits with respect to coffee, tea and other beverages, as well as their exposure to a number of known or suspected risk factors for bladder cancer. After adjustment for tobacco smoking, the relative risk of bladder cancer in relation to coffee drinking was not statistically significant among either men or women. A significant association was found between bladder cancer and tea drinking among men, but with no regular trend for increasing consumption. An association was found between risk of bladder cancer and both total daily liquid intake and non-cola soft drinks. This population-based case-control study provides no evidence of an isolated influence of coffee drinking or caffeine intake on bladder cancer risk.

Short-term effects of air pollution on mortality in Athens.

Abstract: Short-term effects of air pollution on mortality in Athens during the years 1975-1982 were studied. Daily values of sulphur dioxide (SO2) and smoke, measured by a five-station network of the National Observatory of Athens, were used as air pollution indicators. Mortality data were abstracted from the Town Registries of Athens and 18 other contiguous towns within the Greater Athens area. It was found that the adjusted daily mortality (estimated by subtracting from the observed value of mortality an 'expected' value, calculated after fitting a sinusoid curve to the empirical mortality data) depends positively and significantly on the level of SO2 (b = +0.0058, p = 0.05). This relation is independent of temperature, relative humidity, secular, seasonal, monthly and weekly variations of mortality as well as of synergistic effects of the above variables with season. No relation was found between smoke and adjusted daily mortality. An analysis for the determination of a possible threshold in the levels of SO2 causing health effects was also undertaken, by studying changes in the SO2 regression coefficients after successive deletion from the regression model of the days with the highest SO2 values. Our study shows that if there is an SO2 threshold it must lie slightly below the level of 150 micrograms/m3 (mean daily value).

Age, period and cohort models - the use of individual records

Abstract: Problems with the interpretation of age-period-cohort models are discussed. If individual records are available for cancer incidence in Scotland, then a solution is obtainable. An example using incidence data for cancers of the lung and larynx in Scotland is presented to illustrate the models.

Human B lymphocytes immortalization by Epstein-Barr virus in the presence of cyclosporin A.

Abstract: A simple method was devised for the establishment of continuous lymphoblastoid cell lines (LCL). Unfractionated mononuclear cells collected from healthy donors were infected in vitro by Epstein-Barr Virus (EBV) (strain B95-8) under specific conditions: an immunosuppressive drug, Cyclosporin-A (CS-A, Sandoz), associated with the use of a feeder layer (MRC-5) led to 100% efficiency of LCL establishment. A bank of 400 LCL was set up for completion of genetic studies. Regression and kinetics of virus-induced transformation were monitored and related to donors' EBV immune status. Mean time of LCL establishment and probability of regression among seropositive donors were not linked to any given value titer of antibodies against Viral Capsid Antigen (VCA) or against Epstein-Barr Nuclear Antigen (EBNA). However, when the anti-VCA:anti-EBNA ratio was considered, this parameter seemed to be linked to the kinetics of transformation but not to the probability of regression. Once LCL are established, large quantities of human cells can be produced. The complete cellular DNA is available so that any part of it can be scrutinized. Moreover, some of the phenotypic characteristics of these B cells can be used for a wide range of investigations.

Relevance of N-nitrosamines to esophageal cancer in China.

Abstract: Studies on the relevance of the N-nitrosamines to esophageal cancer in China are reviewed. Esophageal cancer is a complex and multifactorial problem. Although a causal association between nitrosamines exposure and esophageal cancer in China has not yet been rigorously established, exposure of Lin-Xian subjects to nitrosamines either directly or as a result of their in vivo formation has been detected in our study. Several N-nitrosamines (NDMA, NDEA, NMBzA, NPyr, NPip, and NSAR) in gastric juice collected from Lin-Xian inhabitants have been detected. A correlation was found between the lesions of esophageal epithelium and the amount of nitrosamines present. In addition, the amounts of N-nitrosamino acids (N-nitrosoproline, N-nitrosothiazolidine 4-carboxylic acid, NSAR, and nitrates) excreted in 24-hr urine of subjects in Lin-Xian were significantly higher than those in Fan-Xian, indicating a higher exposure to N-nitroso compound and their precursors of the inhabitants in the high-risk area. The effect of nitrosamines on human esophagus has been investigated at the cellular levels. The amounts of O6-MedG in DNA of esophageal or stomach mucosa of patients from Lin-Xian were higher than that from Europe (Lyon and Essen). The presence of O6-MedG in the human fetal esophagus cultured with NMBzA was also detected. These findings indicate that the elevated levels of O6-MedG in esophageal DNA could be the result of a recent exposure to N-nitroso compounds or a genetically determined reduced cellular capacity for repair of O6-MedG from DNA. The hyperplasia was induced in the esophagus of human fetus that cultured with NMBzA for 2 weeks to 2 months. The intervention studies of esophageal cancer in Lin-Xian have been pursued. Intake of moderate doses of ascorbic acids by Lin-Xian subjects effectively reduced the urinary levels of N-nitrosamino acids to those found in un-dosed subjects in the low-risk area. If N-nitroso compounds are formed in vivo and are among the causative factors of esophageal cancer in Lin-Xian, ascorbic acid appears to be effective in lowering the body burden of these carcinogenic compounds. Thus, the plan of chemoprevention is carried out in Lin-Xian.

Cancer mortality among white males in the meat industry.

Abstract: A study was conducted among 13,844 members of a meat-cutter's union, from July 1949 to December 1980, to examine cancer occurrence in the meat industry. Separate analyses were carried out for the whole group, and for subgroups defined by job-categories characteristic of the industry, including a control group. Mortality was compared with that of the United States through the estimation of standardized mortality ratios (SMR) and proportional mortality ratios. A statistically significant proportional mortality ratio of 2.9 was obtained for Hodgkin's disease among abattoir workers; the SMR of 2.2 was not significant. Among meat-packing plant workers, highly statistically significant SMRs were recorded for bone cancer, SMR = 9.6; cancer of the buccal cavity and pharynx, SMR = 3.4; and lung cancer, SMR = 1.9. The role of oncogenic viruses and other carcinogenic exposures was investigated.

Monitoring of individual human exposure to aflatoxins (AF) and N-nitrosamines (NNO) by immunoassays.

Abstract: Highly sensitive immunoassays have been used to quantitate aflatoxins (AF) and N-nitrosamines (NNO) in human body fluids and tissues, respectively. This approach was taken in order to quantitate environmental exposure to these agents at an individual level to facilitate the investigation of their role in the etiology of human cancer. In order to analyse AF in human urine, an immunopurification step has been developed by using AF-specific antibody bound to AH-Sepharose 4B gel in a small (4-ml gel volume) affinity column prior to enzyme-linked immunosorbent assay (ELISA). The ELISA can be used to quantitate aflatoxin B1 (AFB1) over the range 0.01 ng/ml to 10 ng/ml and the assay system has been validated by using human urine samples spiked with AFB1 over this concentration range. In addition, 29 urine samples from the Philippines have been analysed and found to contain a range of levels from zero to 4.25 ng/ml AFB1 equivalent with a mean of 0.875 ng/ml. This compared with a mean of 0.066 ng/ml AFB1 equivalent in samples from France. Radioimmunoassay of O6-methyldeoxyguanosine (O6-medG) has been performed on human oesophageal and cardiac stomach mucosal DNA from tissue samples obtained during surgery in Linxian County, People's Republic of China, an area of high risk for both oesophageal and stomach cancer. Using the methodology described and having 1 mg of hydrolyzed DNA allows the detection of approximately 25 fmol O6medG per mg DNA. Of the 37 tissue samples analyzed from Linxian County, 17 samples had levels of O6-medG ranging from 15 to 50 fmol/mg DNA, ten showed higher levels up to 160 fmol/mg DNA, and the remaining ten samples were below the limit of detection. For comparison, 12 tissue samples were obtained from hospitals in Europe and all showed levels below 45 fmol O6-medG/mg DNA with seven below the limit of detection. All tissue samples from Linxian county showed normal levels of O6-alkylguanine DNA alkyltransferase when compared to levels in other parts of the world. The approaches described appear promising for assessing the role of AFB1 in the etiology of human liver cancer and of nitrosamines as possible causative agents in oesophageal or stomach cancer.

Infections due to the Human Herpes-viruses in Southern India: A Seroepidemiological Survey

Abstract: We studied the prevalence of lgG and IgM antibodies to the human herpesviruses in a hospital-based population of 181 individuals aged 0 to 25 years, who were resident in Vellore, south India or surrounding rural areas. Antibodies to the Epstein-Barr virus (EBV) viral capsid antigen were determined by indirect immunofluorescence, while antibodies to the remaining herpesviruses were determined by enzyme-linked immunosorbent assay. The age-specific prevalence rates of IgG antibodies to EBV and cytomegalovirus (CMV) rose rapidly after birth to reach a value of over 90% by the fourth year of life. High age-specific IgM prevalence rates and geometric mean titres (GMT) of IgG antibody in children 6 months to 2 years of age, and the early median age of virus infection (1.4 years for EBV and <1 year for CMV) indicate that primary infection with these viruses occurs early in life. In contrast, age-specific prevalence rates of IgG antibodies to varicella-zoster virus (VZV) and herpes simplex virus (HSV) rose gradually after birth to attain maximal values of only 72% (VZV) and 83% (HSV) in the 15-25 year age group, and the median ages of infection were delayed (12.25 years for VZV and 8.2 years for HSV). The age-specific IgG prevalence rates of VZV and HSV, and of EBV and HSV showed statistically significant positive correlations, suggesting that common epidemiological factors may underlie the pattern of infections due to these groups of viruses. The results of this study provide baseline information on the epidemiology of human herpesvirus infections in a tropical developing country and indicate that they are common and likely to be important causes of morbidity over a wide range of ages. The clinical correlates and importance of these infections in age groups at high risk require further investigation in developing countries.

The man-made mineral fiber European historical cohort study. Extension of the follow-up

Abstract: The study concentrated on 21,967 workers producing rock wool/slag wool, glass wool or continuous filament in 13 European factories. The expected deaths and incident cancer cases were derived from multiplying the accumulated person-years by national reference rates across sex, age, and calendar-year strata, correction factors for regional lung cancer mortality also being used. Exposure assessment was based on the results of a historical environmental investigation reported elsewhere. There were 189 deaths (151.2 expected), and for rock-wool/slag-wool and glass-wool workers the standardized mortality ratios for lung cancer showed a pattern of increasing mortality with time since first exposure but not duration of employment. There was an excess of lung cancer among rock-wool/slag-wool workers employed during an early technological phase before the introduction of dust-suppressing agents, and fiber exposure, either alone on in combination with other exposures, may have contributed to the elevated risk. No excess of the same magnitude was evident for glass-wool production, and the follow-up of the continuous filament cohort was too short to allow for an evaluation of possible long-term effects. There was no evidence of an increased risk for pleural tumors or nonmalignant respiratory diseases.

Case-control studies for estimation of the natural history of preclinical disease from screening data.

Abstract: The duration of the detectable preclinical phase of disease, which we call the sojourn time, is an important quantity to consider when recommending frequency of screens and investigating the natural history of the disease. In this paper, we propose a matched case-control methodology for screening data for joint estimation of the sojourn time distribution and the false negative rate of the screening test. The approach is based on a conditional likelihood for matched sets that involves a comparison of the screening histories of cases and controls. We illustrate the methodology with the data from the Aberdeen screening programme for cervical cancer by the Pap smear. We consider a number of different parametric forms for the sojourn time distribution.

Phenotypic characterization of Ewing sarcoma cell lines with monoclonal antibodies.

Abstract: The histogenesis of Ewing sarcoma, the second most frequent bone tumor in humans, remains controversial. Four Ewing cell lines were analyzed by immunological methods. A panel of antibodies directed to T, B, and myelomonocytic markers gave negative results. Surface antigens recognized on Ewing cells were found to be related to the neuroectoderm lineage. Ganglioside GD2, a marker of neuroectodermal tissues and tumors, was present on all lines. These were also stained by the mouse monoclonal antibody HNK-1, which detects a carbohydrate epitope present on several glycoconjugates of the nervous system, including two glycoproteins, the myelin-associated glycoprotein and the neural cell-adhesion molecule (N-CAM), and an acidic glycolipid of the peripheral nervous system. The P61 monoclonal antibody, which reacts with a peptide moiety of N-CAM, and a rabbit antiserum, raised to purified mouse N-CAM and not recognizing the HNK-1-defined epitope, were also reactive. By contrast, all antibodies specific for hematopoietic cell surface antigens were totally negative. Besides these antigenic features, Ewing sarcoma cells are characterized by a specific t(11:22)(q24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor, suggesting a possible evolutionary related origin. The recent finding that the human N-CAM gene is located at the vicinity of the breakpoint on chromosome 11 indicates that it might be involved in genetic rearrangements occurring in this region.

EBV-negative and -positive burkitt cell lines variably express receptors for B-cell activation and differentiation

Abstract: The expression of receptors for proliferation and differentiation factors was analyzed by indirect immunofluorescence on 29 Burkitt lymphoma (BL) cell lines previously classified into 3 groups on the basis of their reactivity with 8 monoclonal antibodies (MAbs), including anti-CALLA, BL13 and TU1. BL13 and HB5 antibodies recognize different epitopes of the EBV/CR2 receptors. The determinant recognized by BL13 has been previously shown to be expressed only on cell lines of the first two groups, supposed to derive from the germinal center and to be negative on a third group of lines of putative BM origin and established from sporadic cases of BL. In contrast, and as expected from its reactivity on normal B cells in the BM or in the lymph nodes, HB5 antibody reacts with all BL lines except one. The receptor for transferrin is expressed on the 29 lines. Two new MAbs, Bac-1 and B1H5, could recognize respectively receptors for BCGF1 and BCGF2. Bac-1 reacts with 15 of 17 BL lines belonging to the first two groups and 7 of 12 BL lines of the third group; 14 of 15 EBV + lines express Bac-1. No BL line expresses B1H5. The IL2 receptor is weakly expressed on 5 EBV + cell lines and one EBV (-) line. All delta are BCGF1-positive. The almost constant expression of BCGF1 receptor on EBV + cell lines is the only strict relation between the expression of receptors for growth factors and their characteristics (i.e. EBV association, translocation, ethnic origin and clinical presentation). The maturation stage or the origin of BL cell lines in relation to the expression of growth factor receptors and the functional significance of these receptors will be discussed.

Vitamin measurements in pooled blood samples

Abstract: From 610 blood samples collected in September 1983 in an intervention trial in Huixian, Henan Province, People's Republic of China, which were individually analyzed for retinol, beta-carotene, and alpha-tocopherol levels, 10 pools were formed from 50 individual samples, and the vitamin levels in the merged pools were also measured. Oxidation losses by repeated thawing and refreezing render the absolute levels measured in the pools smaller than the corresponding means of the individual measurements. A very good relative agreement was found between pool levels of retinol and beta-carotene and the respective means. The pooling technique could be a valuable tool in large correlation studies and has possible further applications in case-control studies.

Oxidative destruction of hydrazines produces N-nitrosamines and other mutagenic species.

Abstract: As part of the joint International Agency for Research on Cancer-National Cancer Institute program for the evaluation and development of methods for the degradation of chemical carcinogens, four oxidative techniques for the degradation of hydrazines were investigated. The oxidizing agents used were as follows: sodium hypochlorite, calcium hypochlorite, potassium iodate, and potassium permanganate in sulfuric acid. In each case, at least 99% of the hydrazine initially present was destroyed; however, the potential usefulness of these methods was compromised by the formation (in some reaction mixtures) of carcinogenic N-nitroso compounds and/or unknown mutagenic species. Oxidative degradation of hydrazines is recommended only for the decontamination of glassware and for the treatment of spills, for which reductive degradation methods are not suitable.