Showing papers by "International Agency for Research on Cancer published in 1989"

Cancer incidence and mortality in Europe

Abstract: Cet ouvrage de reference, essentiellement descriptif, presente sous une forme principalement graphique, accompagnee de tres brefs commentaires, les elements suivants: 1. les taux d'incidence, standardis es par rapport a la population mondiale, pour 31 localisations ou groupes de localisations cancereuses de 45 regions appartenant a 19 pays europeens qui figurent dans le volume 5 de la serie «Cancer Incidence in Five Continents»; 2. les donnees officielles de mortalite fournies par l'Organisation mondiale de la Sante pour 27 localisations et 26 pays pour la periode correspondant a l'incidence, comprise entre 1978 et 1982. Le supplement fournit egalement les rapports homme/femme d'incidence et de mortalite pour chaque pays et region d'Europe consideres, ainsi que le rang de chaque localisation ou pays/region, respectivement au sein de chaque pays/region ou localisation. Parmi les constatations les plus importantes de ce rapport on relevera: les taux eleves d'incidence et de mortalite par cancer pulmonaire en Ecosse dans les deux sexes et en Angleterre, les plus bas etant enregistres en Scandinavie, Espagne et Italie du Sud; les niveaux eleves des neoplasies liees a l'exposition conjointe au tabac et a l'alcool en France, en Suisse romande, en Italie du Nord et en Ecosse, surtout chez la femme; les taux generalement faibles dans les populations mediterraneennes (Espagne, Italie du Sud et Grece) pour la plupart des autres tumeurs frequentes, notamment de l'estomac, du colorectum et du sein; les rangs particulierement eleves des cancers genitaux en Scandinavie, en Suisse et en Italie du Nord, de l'incidence des tumeurs de la vessie dans les regions a haute concentration d'industries chimiques, des tumeurs thyroidiennes en Scandinavie et en Suisse, et des tumeurs lymphatiques en Ecosse, en Suisse et en Italie du Nord.

Colorectal cancer and diet in an asian population—A case-control study among Singapore Chinese

Abstract: A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.

Calorie-Providing Nutrients and Risk of Breast Cancer

Abstract: A case-control study was conducted in Italy to investigate the role of diet in breast cancer. Cases were 250 women with breast cancer, and controls were a stratified random sample of 499 women from the general population. A dietary history questionnaire was used to measure the intake of total fat, saturated fat, animal proteins, and other macronutrients. In multivariate analyses, the relative risks of breast cancer for women in the highest quintile of consumption of saturated fat and animal proteins were 3.0 (95% confidence interval, 1.9-4.7) and 2.9 (1.8-4.6), respectively. A reduced risk was found for women who derived less than 28% of calories from fat versus greater than 36%. A similarly reduced risk was found for women who derived less than 9.6% of calories from saturated fat or less than 5.9% from animal proteins. These data suggest that during adult life, a reduction in dietary intake of fat and proteins of animal origin may contribute to a substantial reduction in the incidence of breast cancer in population subgroups with high intake of animal products.

Human carcinogens so far identified.

Abstract: The massive exploitation of natural resources, of which tobacco and asbestos are two conspicuous, though very different examples, and the synthesis of industrial chemicals have generated new hazards and new carcinogens which have been added to older ones. The majority of the over 50 agents that have been firmly identified so far as being human carcinogens belong to the relatively new hazards, that is environmental chemicals or chemical mixtures to which humans have been exposed only during the last century and a half. They are of more importance for cancer occurring in men than in women, and there is no evidence so far that they are related to cancers occurring at some of the most common target sites in either sex. It would be mistaken to believe that complete cancer prevention could be achieved solely by controlling these new, or relatively new, carcinogenic agents, but it would be similarly wrong to deny the importance of trying to control them and of continuing to do so. The experimental approach for the identification of carcinogens has an irreplaceable role to play in preventing the dispersal into our environment of new hazards and in identifying among the chemicals already in use, those that are carcinogenic. That a closer integration between the epidemiological and the experimental approaches may succeed in substantially reducing the size of the unknown region within the spectrum of cancer-causing factors, is today's hope that awaits confirmation. At the same time, advances in the understanding of the mechanisms underlying the different steps of the process leading to the clinical manifestation of cancer may help in the uncovering of agents and risk factors that the approaches used, at least in the way they have been used until now, may not have been apt to identify.

A case-control study of diet and breast cancer in Argentina.

Abstract: A case-control study of breast cancer was carried out in La Plata, Argentina, where the incidence of the disease is comparable to the highest rates recorded worldwide. One hundred and fifty incident cases were identified through major hospitals. For each case, a hospital control, matched by age and hospital, and a neighbourhood control, matched by residential area and age, were also chosen. Cases and controls were interviewed to obtain information on past diet, as well as demographic and socio-economic characteristics, reproductive and menstrual history and other potential breast-cancer risk factors. The dietary information was obtained from questions on the consumption of specific food items and information on portion sizes from an earlier study was used to estimate intake of calories and selected nutrients. There was a substantial excess energy intake among cases as compared to both control groups, which was present across all 3 major macronutrients which contribute to total calories. Among the food groups, the consumption of eggs was a risk factor for breast cancer, and wholemilk products and green leafy vegetables were protective. After adjusting for the calorie difference in multivariate statistical analyses of nutrients, fibre and betacarotene consumption were weakly protective. The results are discussed with reference to possible methodological difficulties and previous studies of diet and breast cancer.

Leukaemia and residence near electricity transmission equipment: a case-control study

Abstract: A population-based case-control study of leukaemia and residential proximity to electricity supply equipment has been carried out in south-east England. A total of 771 leukaemias was studied, matched for age, sex, year of diagnosis and district of residence to 1,432 controls registered with a solid tumour excluding lymphoma; 231 general population controls aged 18 and over from one part of the study area were also used. The potential for residential exposure to power frequency magnetic fields from power-lines and transformer substations was assessed indirectly from the distance, type and loading of the equipment near each subject's residence. Only 0.6% of subjects lived within 100 m of an overhead power-line, and the risk of leukaemia relative to cancer controls for residence within 100 m was 1.45 (95% confidence interval (CI) 0.54-3.88); within 50 m the relative risk was 2.0 but with a wider confidence interval (95% CI 0.4-9.0). Over 40% of subjects lived within 100 m of a substation, for which the relative risk of leukaemia was 0.99. Residence within 25 m carried a risk of 1.3 (95% CI 0.8-2.0). Weighted exposure indices incorporating measures of the current load carried by the substations did not materially alter these risks estimates. For persons aged less than 18 the relative risk of leukaemia from residence within 50 m of a substation was higher than in adults (PR = 1.5, 95% CI 0.7-3.4).

Human exposure to endogenous N-nitroso compounds: quantitative estimates in subjects at high risk for cancer of the oral cavity, oesophagus, stomach and urinary bladder.

Abstract: A sensitive procedure to quantitate human exposure to endogenous N-nitroso compounds (NOC) has been developed. It is based on the excretion of N-nitrosoproline (NPRO) and other N-nitrosamino acids in the urine, which are measured as an index of endogenous nitrosation, following ingestion of precursors. The NPRO test has been applied to human subjects in clinical and epidemiological studies, and the kinetics and dietary modifiers of endogenous nitrosation have been investigated. Results obtained after application of the NPRO test to subjects at high risk for cancers of the stomach, oesophagus, oral cavity and urinary bladder are summarized. In most instances, higher exposures to endogenous NOC were found in high-risk subjects, but individual exposure was greatly affected by dietary modifiers or disease state. Vitamin C efficiently lowered the body burden of intragastrically formed NOC. The results point to an aetiological role of NOC in these human cancers and provide an interpretation of epidemiological findings that have shown protective effects of fruits and vegetables against several malignancies.

Epidemiology of pancreas cancer (1988).

Abstract: This article reviews the epidemiology of cancer of the pancreas, both descriptive and analytical, at all times cognizant of the problems of misdiagnosis, particularly underdiagnosis, of this lethal disease that continue to hinder epidemiological studies. Pancreas cancer is consistently reported to occur more frequently in men than in women, in blacks than in whites, and in urban rather than rural population groups. In some countries, the mortality rates continue to rise, whereas in others, declining levels of disease can be seen among members of younger birth cohorts. Although some of these patterns can be explained by variation in pancreas cancer risk factors, many cannot. Analytical studies consistently demonstrate that cigarette smoking increases the risk of cancer of the pancreas, and this appears, at the present time, to be the only clearly demonstrated risk factor for pancreatic cancer. Although the association with disease risk and coffee consumption, alcohol consumption, occupational exposures, diabetes, pancreatitis, and other factors requires clarification, it appears likely that the most fruitful research area in the coming years may involve exploration of pancreatic cancer risk and nutritional practices.

The international comparability of cancer mortality data results of an international death certificate study

Abstract: In preparation for the 10th revision of the International Classification of Diseases (ICD-10), a two-part study was undertaken to assess the international comparability of the coding, by the 9th revision (ICD-9), of death certificates mentioning cancer, to see whether there had been improvement since the 8th revision (ICD-8). Part I repeated a 1978 study in which nine countries coded the same 1,234 United States death certificates mentioning cancer by ICD-9. The proportion of disagreements in coding the underlying cause of death fell about 35% between 1978 and the present study. This reduction was probably due to the new more detailed rules for coding cancer death certificates given in ICD-9. To combat the criticism of the possible bias associated with using United States death certificates only, in Part II of the study, each of seven countries submitted about 100 certificates translated into English which had posed problems in coding cancer. Discrepancies in assigning the underlying cause of death were found for 54% of these problem certificates. The major types of problems identified were coding when multiple cancer sites were mentioned on the death certificate, whether to select heart disease or cancer as the underlying cause of death, and the interpretation of the coding rules. Better rules for ICD-10 must be provided for both physicians and coders if international comparability of cancer mortality data is to be achieved.

Effect of a malaria suppression program on the incidence of african burkitt's lymphoma

Abstract: From 1977 to 1982, the authors attempted a malaria suppression trial in North Mara District, Tanzania, to see whether the incidence of Burkitt's lymphoma (BL) could be lowered by reducing the level of malarial infection in a child population below 10 years of age. Immediately after initiation of the suppression trial, the prevalence of malaria fell drastically in the Mara children; however, soon after, the rate of malarial infection rose again in the trial area in spite of continued chloroquine distribution, and by 1981 the prevalence of malarial infection again reached the high levels that had prevailed in the North Mara lowlands before 1977. However, during the period of chloroquine distribution in North Mara, the level of malarial infection there was constantly lower than that observed in a comparison area in South Mara, although the two areas had been similar with respect to malaria endemicity prior to the intervention. During the years of chloroquine distribution in North Mara, the incidence rate of BL there fell considerably, from about 4 per 100,000 population to about 1 per 100,000 population, and it rose again to pretrial levels in 1984, that is, about two years after the chloroquine distribution had been terminated. This apparent association between malaria suppression and decline in BL incidence at first seemed to indicate that malaria is a causal factor in BL production. A close scrutiny of the survey data revealed, however, that the decline in BL incidence might have started several years before the chloroquine distribution began; thus it appears that the malaria suppression could not have been the sole cause of the BL decline.

Alkyl and aryl carcinogen adducts detected in human peripheral lung

Abstract: Human peripheral lung tissue samples were obtained at autopsy from 17 individuals of known occupational and smoking histories. A spectrum of different carcinogen-DNA adducts was detected using a variety of sensitive techniques. High-pressure liquid chromatography-linked synchronous fluorescent spectrophotometry and an ultrasensitive enzyme radioimmunoassay detected adducts derived from benzo[a]pyrene diol epoxide and other apparent polycyclic aromatic hydrocarbons. An amplified enzyme-linked immunosorbent assay demonstrated the presence of 4-aminobiphenyl-DNA adducts in many of these samples. A number of these specimens also contained O6-alkyldeoxyguanosine as measured by 32P-postlabeling techniques. Thus this pilot study indicates not only that human lung contains a spectrum of carcinogen-DNA adducts, but also that a full scale molecular dosimetry study of human exposure to both aryl and alkyl chemical carcinogens is warranted.

1,N6-etheno-2'-deoxyadenosine and 3,N4-etheno-2'-deoxycytidine detected by monoclonal antibodies in lung and liver DNA of rats exposed to vinyl chloride.

Abstract: 1,N6-Etheno-2'-deoxyadenosine (epsilon dAdo) and 3,N4-etheno-2'-deoxycytidine (epsilon dCyd) are formed in vitro by reaction of DNA with the electrophilic metabolites of vinyl chloride (VC), chloroethylene oxide and chloroacetaldehyde To detect and quantitate these DNA adducts in vivo, we have raised a series of specific monoclonal antibodies (Mab) Among those, Mab EM-A-1 and Mab EM-C-1, respectively, were used for detection of epsilon dAdo and epsilon dCyd by competitive radioimmunoassay (RIA), following pre-separation of the etheno adducts from DNA hydrolysates by high performance liquid chromatography At 50% inhibition of tracer-antibody binding, both Mab had a detection limit of 187 fmol and antibody affinity constants (K) of 2 x 10(9) l/mol The levels of epsilon dAdo and epsilon dCyd were quantitated in the DNA of lung and liver tissue of young Sprague-Dawley rats exposed to 2000 ppm of VC for 10 days The epsilon dAdo/2'-deoxyadenosine and epsilon dCyd/2'-deoxycytidine molar ratios were 13 x 10(-7) and 33 x 10(-7), respectively, in lung DNA, and 50 x 10(-8) and 16 x 10(-7) in liver DNA When hydrolysates of 3 mg of DNA were analyzed by RIA at 25% inhibition of tracer-antibody binding, epsilon dAdo and epsilon dCyd were not detected in liver DNA from untreated rats above the limiting epsilon dAdo/2'-deoxyadenosine and epsilon dCyd/2'-deoxycytidine molar ratios of 22 x 10(-8) and 31 x 10(-8), respectively

Screening for Lung Cancer

Abstract: Lung cancer incidence is increasing. Survivability has increased over the last few years particularly in certain subsets and has also been shown to increase with early detection. Chest X-ray and sputum cytology have been the mainstays of screening programs. Although survival is increased, overall mortality rates seem unchanged except in certain subsets. Whether the addition of serum markers or use of monoclonal antibodies, automated cytological, and computer-aided techniques will show decrease in mortality remains to be documented. We recommend yearly chest X-rays, sputum cytology in high-risk patients, i.e., age greater than 65, greater than 20 year history smoking, other significant carcinogenic exposure. Serum markers, monoclonal antibodies, and advanced, automated cytology methods are yet to be tested and therefore should be considered in clinical trials only.

Changes in gap junction protein (connexin 32) gene expression during rat liver carcinogenesis.

Abstract: A rat liver gap junction (GJ) cDNA probe that detects mRNA encoding the 32 Kd GJ-protein (connexin 32) was employed to study GJ-protein gene expression in rat liver tumors induced by a single exposure to diethylnitrosamine (DEN) followed by exposure to 2-acetylaminofluorene (AAF)/CCl4/AAF or induced by systemic administration of N-ethyl-N-hydroxyethylnitrosamine (EHEN). All carcinomas generated by these carcinogens showed markedly reduced levels of GJ-protein mRNA. This may indicate that GJ-protein levels and gap-junctional intercellular communication (GJIC) capacity are also severely compromised. Moreover, all hyperplastic nodules also showed a reduced level of GJ-protein mRNA. Taken together with our earlier finding that the liver tumor promoter phenobarbital inhibits GJ-protein gene expression, these results suggest that deranged GJIC is a relatively early event in liver multistage carcinogenesis. A range of other cDNA probes was also used to characterize gene expression in the DEN-induced tumors. Induction of expression was seen for glutathione S-transferase (placental form) (GST-P), gamma-glutamyltranspeptidase (GGT), and c-raf but not for c-Ha-ras or c-myc.

Prevalence of genotoxic chemicals among animal and human carcinogens evaluated in the IARC Monograph series.

Abstract: To determine whether genotoxic and non-genotoxic carcinogens contribute similarly to the cancer burden in humans, an analysis was performed on agents that were evaluated in Supplements 6 and 7 to the IARC Monographs for their carcinogenic effects in humans and animals and for the activity in short-term genotoxicity tests. The prevalence of genotoxic carcinogens on four groups of agents, consisting of established human carcinogens (group 1, n = 30), probable human carcinogens (group 2A, n = 37), possible human carcinogens (group 2B, n = 113) and on agents with limited evidence of carcinogenicity in animals (a subset of group 3, n = 149) was determined. A high prevalence in the order of 80 to 90% of genotoxic carcinogens was found in each of the groups 1, 2A and 2B, which were also shown to be multi-species/multi-tissues carcinogens. The distribution of carcinogenic potency in rodents did not reveal any specific characteristic of the human carcinogens in group 1 that would differentiate them from agents in groups 2A, 2B and 3. The results of this analysis indicate that (a) an agent with unknown carcinogenic potential showing sufficient evidence of activity in in vitro / in vivo genotoxicity assays (involving as endpoints DNA damage and chromosomal/mutational damage) may represent a hazard to humans; and (b) an agent showing lack of activity in this spectrum of genotoxicity assays should undergo evaluation for carcinogenicity by rodent bioassay, in view of the present lack of validated short-term tests for non-genotoxic carcinogens. Overall, this analysis implies that genotoxic carcinogens add more to the cancer burden in man than non-genotoxic carcinogens. Thus, identification of such genotoxic carcinogens and subsequent lowering of exposure will remain the main goal for primary cancer prevention in man.

Epidemiology of cervical cancer.

Abstract: Cervical cancer is on the rise worldwide and is estimated to comprise of all cancers the number of new cases of cervical cancer per year is around 465000 20% of these cases occur in developed countries with 80% in developing countries Cervical cancer presently ranks 5th; 73% of all human cancers worldwide In Africa Central and South America Asia and outside Japan cervical cancer is the leading cancer among women and constitutes 20-30% of all cancers in women Contrasting figures exist for North America Australia Northern and Western Europe with cervical cancer accounting for 4-6% of all female cancers Estimates are crude because of poor assessment of population and incidences of cervical cancer in certain areas of the world With larger populated areas differences are not as easily detected between small geographical unites such as regions countries or population groups classified by ethnicity religious origin or residential status Epidemiological evidence indicates that number of womens sexual partners age of first intercourse smoking long-term oral contraceptive use dietary factors and immunosuppressants are the principal determinants of womens cervical cancer risk How each of these determinants contribute to cervical cancer cannot be adequately assessed with data There is some evidence of an association between cervical cancer and various infectious agents including syphilis herpes simplex virus 2 and chlamydia trachomatis

Levels of mutagens in the urine of smokers of black and blond tobacco correlate with their risk of bladder cancer

Abstract: Levels of urinary mutagens, thioethers, N-nitrosamino acids, nitrate, nicotine, cotinine and creatinine were measured in 21 non-smokers, 26 smokers of blond tobacco, 9 smokers of black tobacco and 5 smokers of both types of tobacco, all eating a similar diet. Results were expressed either per 24 h urine or per mmol creatinine. The sum of urinary nicotine and cotinine levels (N + C) was used as a measure of exposure to the number of cigarettes smoked. Statistically significant positive dose-effect relationships were obtained between the urinary N + C levels and (i) the number of revertants (Salmonella typhimurium TA98, with a metabolic activation system); (ii) the concentration of thioethers; (iii) the levels of N-nitrosoproline or the sum of all nitrosamino acids excreted and (iv) the amount of urinary nitrate. No such correlation was found between N + C levels and induction potency in the SOS chromotest. A linear dose-effect relationship between urinary mutagenicity (i.e. log revertants of S. typhimurium TA98) and N + C levels or number of cigarettes per day was established for smokers of blond tobacco. After adjustment for N + C levels, the urine of smokers of black tobacco contained twice as much mutagenic material as did the urine of blond tobacco smokers (P = 0.02). For other exposure markers, no statistically significant difference was found between the two types of smokers. Epidemiological studies have shown that the risk of urinary bladder cancer is 2.5 times higher in smokers of black tobacco than in blond tobacco. Therefore, our findings on urinary mutagenicity provide experimental evidence that the type of tobacco is the factor responsible for the observed difference in risk and that smoking of black as compared to blond tobacco results in a higher exposure of the urinary bladder to genotoxic hence potentially carcinogenic substances.

Radiation dose and breast cancer risk in patients treated for cancer of the cervix.

Abstract: The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based ...

Volatile nitrosamine levels and genotoxicity of food samples from high‐risk areas for nasopharyngeal carcinoma before and after nitrosation

Abstract: Traditional life-style, especially food habits, infection by Epstein-Barr virus (EBV) and genetic factors, have been associated with an increased risk of nasopharyngeal carcinoma (NPC). N-Nitroso compounds and other carcinogens either present in food or formed endogenously, as well as food constituents that activate EBV, have been suspected as etiological factors in NPC pathogenesis. For their characterization preserved food items, frequently consumed in NPC endemic areas in Tunisia, South China and Greenland, were sampled and screened for the presence of mutagens and volatile nitrosamines before and after nitrosation. Aqueous extracts as well as 2 organic extracts of the samples were assayed for genotoxicity in 2 Salmonella typhimurium strains and the SOS chromotest. The same extracts had previously been analyzed for volatile nitrosamines and for EBV-activating substances in Raji cells. In our study, 13 out of 16 food samples showed a weak, directly-acting genotoxicity in the SOS chromotest in at least one of the extracts, but only one sample from Greenland was found to be weakly mutagenic in Salmonella TA 98. Chemical nitrosation for 9 out of 15 samples of aqueous food extracts increased the genotoxic effect in the SOS chromotest. Levels of volatile nitrosamines were also elevated for 12 out of 15 samples; highest levels of N-nitrosodimethylamine were found in hard salted and dried fish from China (1,200 micrograms/kg) and highest N-nitrosopyrrolidine levels in a Tunisian spice (3,840 micrograms/kg). In non-nitrosated aqueous food extracts, the level of volatile nitrosamines and genotoxic activities were not correlated with the EBV-inducing activity of the same samples. After chemical nitrosation, EBV-inducing activity was decreased or showed no change and was not correlated with increases in either the genotoxicity or the nitrosamine levels. Our results suggest that EBV-activating compounds belong to a different class of substances. However, there was an association between the changes in genotoxicity and nitrosamine levels due to nitrosation.

Passive smoking and lung cancer: current evidence and ongoing studies at the International Agency for Research on Cancer.

Abstract: The evidence available from 3 cohort and 11 case-control studies investigating the relationship between exposure to environmental tobacco smoke (ETS) and lung cancer in non-smokers is reviewed. While it appears most likely that a causal relationship exists, the size of the effect, under different circumstances of exposures, remains to be accurately estimated. This requires studies using valid instruments (e.g., questionnaires) to quantitate exposures, and free as far as possible from biases. An investigation addressing this point is in progress under the coordination of the International Agency for Research on Cancer.

Screening for multiple endocrine neoplasia type 2A with DNA-polymorphism analysis.

Abstract: Multiple endocrine neoplasia type 2a has been shown to be genetically linked to a locus near the centromere of chromosome 10. The availability of polymorphic DNA probes for the region permits the use of restriction-fragment–length polymorphisms (RFLP) to identify carriers of the gene for this cancer syndrome. As part of a French national program, DNA probes were used in a genetic-linkage study of 130 members of 11 families of European and North African origin. In these families there was no recombination between the mutation causing multiple endocrine neoplasia type 2a and two of the three probes used. All 11 families were informative for at least one of the three markers, and linkage information was adequate to provide genetic counseling to 8 families. We found that RFLP analysis is much more useful in predicting the carrier state than conventional endocrine challenge, especially in younger people, but accuracy is maximal when both methods are employed. We conclude that genetic screening allows ...

Overview of perinatal and multigeneration carcinogenesis.

Abstract: One of the characteristics of recent decades, which have seen a formidable expansion of cancer research, has been the co-existence of the generally agreed hypothesis that most cancers are multifactorial in origin, with the attitude of concentrating nevertheless on single carcinogenic agents and on attempting to quantify cancer risks as if they were due to single factors. It is not possible at present to quantitatively estimate the role of prenatal exposures to carcinogens/mutagens in determining or modulating the risk of cancer in humans. It is not unreasonable to assume, however, that the consequences of prenatal exposures and of prenatal events are among the factors that are often ignored. Prenatal events can contribute to the occurrence of cancer as the consequence of either: (1) the direct exposure of embryonal or fetal cells to a carcinogenic agent; (2) a prezygotic exposure of the germ cells of one or both parents to a carcinogen/mutagen before mating; (3) a genetic instability and/or a genetic rearrangement resulting from selective breeding which may favour a deregulation of cellular growth and differentiation. By offering the possibility of investigating the role played by events involving both germ and somatic cells, studies on prenatal carcinogenesis may become essential for a more accurate estimation of risks attributable to environmental agents, and may at the same time contribute to the understanding of some of the mechanisms underlying the genetic predisposition to cancer.

Linkage analysis of seven kindreds with the X-linked lymphoproliferative syndrome (XLP) confirms that the XLP locus is near DXS42 and DXS37.

Abstract: Analysis of seven kindreds indicates that the XLP locus exhibits 1% recombination with DXS42 (lod = 17.5) and no recombination with DXS37 (lod = 13.3).

Carcinogenicity of iron in conjunction with a chlorinated environmental chemical, hexachlorobenzene, in c57bl/10scsn mice

Abstract: Pre-loading of C57BL/10ScSn mice with iron greatly sensitizes them to the induction of hepatic porphyria caused by hexachlorobenzene (HCB) (Smith and Francis, 1983). HCB will also cause liver tumours in experimental animals. Elevated liver iron stores are implicated in the development of some human liver cancers. To determine whether iron overload will potentiate the hepatocarcinogenicity of HCB, male C57BL/10ScSn mice received a single dose of iron-dextran complex or the dextran carrier and were then fed HCB in the diet (0.01%) for up to 18 months. A very clear potentiation by iron of liver tumour incidence occurred. Of the mice which received HCB, but no iron, for 12 months a low incidence of liver hyperplastic nodules was observed, whereas preadministration of iron increased the incidence. After 18 months, all surviving mice initially given iron followed by HCB developed advanced hepatic nodules and 90% had hepatocellular carcinomas. No tumours were seen in animals that only received HCB. Nodules were not seen in iron-dosed mice receiving control diet, but another novel observation was that these animals developed porphyria by 6 months. Although iron enhanced tumour formation in the presence of HCB, the foci, nodules and carcinomas formed all excluded iron. Preliminary studies with the DBA/2 strain suggested that these mice were considerably less susceptible to potentiation by iron.

Relative value of incidence and mortality data in cancer research

Abstract: Cancer surveillance has played an important role in programmes of cancer control, ranging from aiding formulation of current hypotheses regarding the nature of the causes of cancer to assessing the effectiveness of cancer treatment regimes and cancer prevention programmes. Central to this has been the contribution from routine data collection schemes, particularly cancer mortality data and cancer registration schemes, the latter providing cancer incidence statistics for a variety of international populations. Criticisms have been made of the quality of cancer incidence data and there have been suggestions that cancer surveillance may be better achieved by use of mortality data. From examination of the reliability and quality of mortality data, it would appear that international variation in the quality of death certification and in the application of internationally agreed rules for selecting the underlying cause of death may in themselves be enough to vitiate the argument that there is significant international variation in cancer levels or to indicate variation where none in reality may exist. Good cancer incidence data are vitally important to descriptive epidemiology as are good cancer mortality data. It is important to recognize that there are limitations to both types of data which vary both temporarily and internationally. Cancer surveillance and the assessment of the impact of cancer control programmes depend on the reliability of descriptive epidemiology and would best be achieved by maintaining current, population-based cancer registration schemes and, if and where possible, extending such schemes to other populations or population groups. Maximum benefit would be achieved by simultaneous improvement in the quality of mortality data.