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Showing papers by "International Agency for Research on Cancer published in 1994"


Journal ArticleDOI
TL;DR: Nitric oxide (NO) and other oxygen radicals produced in infected and inflamed tissues could contribute to the process of carcinogenesis by different mechanisms, which are discussed on the basis of authors' studies on liver fluke infection and cholangiocarcinoma development.
Abstract: Infection by bacteria, parasites or viruses and tissue inflammation such as gastritis, hepatitis and colitis are recognized risk factors for human cancers at various sites. Nitric oxide (NO) and other oxygen radicals produced in infected and inflamed tissues could contribute to the process of carcinogenesis by different mechanisms, which are discussed on the basis of authors' studies on liver fluke infection and cholangiocarcinoma development. A similar mechanism could apply to other suspected and known cancer-causing agents including Helicobacter pylori infection (stomach cancer) or asbestos exposure (lung mesothelioma). Studies on the type of tissue and DNA damage produced by NO and by other reactive oxygen species are shedding new light on the molecular mechanisms by which chronic inflammatory processes may initiate or enhance carcinogenesis in humans.

1,080 citations


Journal Article
TL;DR: A data base is described in which over 2,500 mutations in the p53 gene of human tumors and tumor cell lines are compiled from a systematic search of reports published before 1 January 1994.
Abstract: A data base is described in which over 2,500 mutations in the p53 gene of human tumors and tumor cell lines are compiled from a systematic search of reports published before 1 January 1994. Data from 1994 are being added intermittently, with a systematic search and update scheduled for December, 1994. The compilation has been deposited with the EMBL Data Library and is available in electronic form free of charge. This report contains a rationale for the compilation, a brief summary of the major findings and a description of the data base.

942 citations



Journal ArticleDOI
TL;DR: It is confirmed that subtyping of IM is useful for identifying individuals at high risk for gastric cancer and the RR was especially increased for a subgroup of type III secreting sulphomucins in their goblet cells in comparison with types I‐II negative to sulphomUCins.
Abstract: Between 1967 and 1976, 1,525 Slovenian patients with a histological diagnosis of intestinal metaplasia (IM) were classified according to subtype of IM based on morphology and mucin staining; 518 cases were diagnosed with type I, 197 with type II and 275 with type III, but in 291 the diagnosis of IM was not confirmed. Patients who had developed cancer or died up to 1986 were identified by record linkage at the Slovenia Cancer Registry and the Central Population Registry in Slovenia. A total of 34 incident cases of gastric cancer occurring at least 6 months after the diagnosis of IM were identified. The standardised incidence ratio (SIR) for stomach cancer was 2.23 in the whole cohort. It was highest for IM type III, followed by type II and IM-unconfirmed, but not increased for type I. The relative risk (RR) of developing gastric cancer based on Cox's proportional hazards model was 2.14 for type II and 4.58 for type III, compared with type I. The RR was especially increased for a subgroup of type III secreting sulphomucins in their goblet cells in comparison with types I-II negative to sulphomucins. Our results confirm that subtyping of IM is useful for identifying individuals at high risk for gastric cancer. © 1994 Wiley-Liss, Inc.

449 citations


Journal ArticleDOI
TL;DR: Overall, the incidence of cancer was increased by 16% in the cohort and the results were essentially unchanged by restriction to the subcohort of 8207 persons in whom obesity was the primary discharge diagnosis, and were also similar in the first year of follow-up after hospital discharge.

432 citations


Journal ArticleDOI
TL;DR: The results suggest that specific p53 gene mutations associated with human skin cancer are induced in normal skin by solar UV radiation.
Abstract: Many human skin tumors contain mutated p53 genes that probably result from UV exposure. To investigate the link between UV exposure and p53 gene mutation, we developed two methods to detect presumptive UV-specific p53 gene mutations in UV-exposed normal skin. The methods are based on mutant allele-specific PCRs and ligase chain reactions and designed to detect CC to TT mutations at codons 245 and 247/248, using 10 micrograms of DNA samples. These specific mutations in the p53 gene have been reported in skin tumors. CC to TT mutations in the p53 gene were detected in cultured human skin cells only after UV irradiation, and the mutation frequency increased with increasing UV dose. Seventeen of 23 samples of normal skin from sun-exposed sites (74%) on Australian skin cancer patients contained CC to TT mutations in one or both of codons 245 and 247/248 of the p53 gene, and only 1 of 20 samples from non-sun-exposed sites (5%) harbored the mutation. None of 15 biopsies of normal skin from non-sun-exposed or intermittently exposed sites on volunteers living in France carried such mutations. Our results suggest that specific p53 gene mutations associated with human skin cancer are induced in normal skin by solar UV radiation. Measurement of these mutations may be useful as a biologically relevant measure of UV exposure in humans and as a possible predictor of risk for skin cancer.

350 citations


Journal ArticleDOI
TL;DR: Empirical evidence linking sun exposure and skin cancer coming from both descriptive studies in populations and analytical studies involving estimates of exposure in individuals is examined, with particular attention given to the quality of the published data.
Abstract: Non-melanocytic skin cancer has long been regarded as one of the harmful effects of solar ultraviolet (UV) radiation on human health. In this review, we examine epidemiologic evidence linking sun exposure and skin cancer coming from both descriptive studies in populations and analytical studies involving estimates of exposure in individuals. Particular attention is given to the quality of the published data. The epidemiologic evidence that sun exposure causes skin cancer is mainly indirect. Incidence or mortality is inversely related to latitude in populations of mainly European origin (e.g., the United States, Australia), and is higher in people born in Australia (high ambient solar radiation) than in migrants to Australia from the United Kingdom (lower ambient radiation). Skin cancer occurs mainly at sun-exposed body sites and in people who are sensitive to the sun; a reduced capacity to repair UV-induced DNA damage appears to increase the risk. The direct evidence linking sun exposure and skin cancer is weaker with few well-conducted studies of sun exposure in individuals. Mostly, studies of total sun exposure have not found statistically significant positive associations; those that did, had not adjusted for potential confounding by age and gender and thus their interpretation is limited. Studies of occupational sun exposure had relative risks not greater than 2.0; recreational exposure has been little studied. Other measurements, less direct but potentially less prone to measurement error, are sunburn (not evidently associated with skin cancer risk) and indicators of benign cutaneous sun-damage (strongly associated but lacking empirical evidence that sun exposure is their main cause). Many questions remain about the relationship between sun exposure and skin cancer.Cancer Causes and Control 1994, 5, 367–392

308 citations


Journal ArticleDOI
27 May 1994-Science
TL;DR: The frequency of the AGG to AGT mutation at codon 249 paralleled the level of AFB1 exposure, which supports the hypothesis that this toxin has a causative--and probably early--role in hepatocarcinogenesis.
Abstract: Fifty-eight percent of hepatocellular carcinomas (HCCs) from Qidong, China, contain an AGG to AGT mutation at codon 249 of the p53 tumor suppressor gene, a mutation that is rarely seen in HCCs from Western countries. The population of Qidong is exposed to high levels of aflatoxin B1 (AFB1), a fungal toxin that has been shown to induce the same mutation in cultured human HCC cells. To investigate the role of AFB1 and of these p53 mutations in hepatocarcinogenesis, normal liver samples from the United States, Thailand, and Qidong (where AFB1 exposures are negligible, low and high, respectively) were examined for p53 mutations. The frequency of the AGG to AGT mutation at codon 249 paralleled the level of AFB1 exposure, which supports the hypothesis that this toxin has a causative--and probably early--role in hepatocarcinogenesis.

281 citations


Journal ArticleDOI
TL;DR: Unless tobacco‐control efforts in developing countries are strengthened, the massive rise in cigarette consumption over the last few decades will produce a comparable rise in cancer in these countries within the next 20 to 30 years.
Abstract: Tobacco smoking is accepted as a major cause of cancers of the lung, larynx, oral cavity and pharynx, oesophagus, pancreas, kidney and bladder. The proportions of these cancers that are due to smoking were estimated for the year 1985 for 24 areas of the world. Fifteen percent--1.1 million new cases per year--of all cancer cases are attributed to cigarette smoking, 25% in men and 4% in women. In developed countries, the tobacco burden is estimated at 16% of all annual incident cases. In developing countries, the corresponding figure is 10%. In total, 85% of the 676,000 cases of lung cancer in men are attributable to tobacco smoking. The highest attributable fractions (AF: 90-93%) are estimated in areas where the habit of cigarette smoking in men has been longest established: North America, Europe, Australia/New Zealand and the former USSR. Among the other 6 cancer sites considered in this analysis, those with the largest fractions of tobacco-related cases are the larynx, mouth and pharynx (excluding nasopharynx) and oesophagus. In regions where males have smoked for several decades, 30 to 40% of all cancers in this sex are attributable to tobacco. Unless tobacco-control efforts in developing countries are strengthened, the massive rise in cigarette consumption over the last few decades will produce a comparable rise in cancer in these countries within the next 20 to 30 years.

273 citations


Journal ArticleDOI
12 May 1994-Nature
TL;DR: The results indicate that the clearance of low-dose carcinogens is decreased in the genetically based slow-acetylator phenotype, which is relevant to ‘risk assessment’ procedures.
Abstract: THE metabolic activation or inactivation of carcinogens varies considerably in human populations, and is partly genetically determined1,2. Inter-individual variability in the susceptibility to carcinogens may be particularly important at low degrees of environmental exposure. Examples of probable human carcinogens that present widespread low-dose exposures are environmental tobacco smoke and diesel exhaust3,4. We have determined levels of DNA adducts in bladder cells and of 4-aminobipheny7l–haemo-globin adducts in 97 volunteers, together with the N-acetylation non-inducible phenotype, the corresponding genotype, and the levels of nicotine–cotinine in the urine. We find that among the slow acetylators, 4-aminobiphenyl adducts were higher than in rapid acetylators at low or null nicotine–cotinine levels, whereas the difference between slow and rapid acetylators was less evident at increasing nicotine–cotinine levels. The N-acetyltransferase genotype is highly predictive of the acetylation phenotype. Our results indicate that the clearance of low-dose carcinogens is decreased in the genetically based slow-acetylator phenotype. Such genetic modulation of low-dose environmental risks is relevant to ‘risk assessment’ procedures.

267 citations


Journal ArticleDOI
TL;DR: In this article, the p53 mutations in cancers of factory workers with a history of carcinogen exposure in the workplace were found in exons 5-8 of the MDM2 gene.
Abstract: Mutations in the p53 tumor suppressor gene are commonly found in the major human cancers and the mutational spectrum in some cancer types is consistent with the genotoxic effects of the associated environmental risk factors. Thus far there is little information on p53 mutations in cancers of factory workers with a history of carcinogen exposure in the workplace. Occupational exposure to vinyl chloride causes liver angiosarcomas (ASL) and also increases the risk of several other cancers. Loss of p53 function in osteo- and fibrosarcomas can occur by two different mechanisms, p53 mutation and amplification of the MDM2 gene. We examined tumors from five vinyl chloride-exposed patients, four with ASL and one with hepatocellular carcinoma (HCC), for evidence of MDM2 proto-oncogene amplification or p53 mutation in exons 5-8. Amplification of MDM2 was not found, but in two of the angiosarcomas an A:T to T:A missense mutation was detected. p53 sequence analysis of vinyl chloride associated cancers may provide valuable information on the relationship between carcinogen exposure and DNA damage in cancer-related genes.

Journal ArticleDOI
TL;DR: In this article, the authors examined and combined the results of the epidemiologic studies conducted on asphalt workers and roofers in various countries, and examined the cancer risk separately in three broad job categories: 1) roofers (exposed to bitumen fumes and previously often to coal-tar fumes); 2) highway maintenance workers (HMWs), and 3) miscellaneous and unspecified bitumen/asphalt workers.
Abstract: Twenty epidemiologic studies have described cancer risk in asphalt workers and roofers in various countries. A current concern for these workers is the potential carcinogenicity posed by inhalation of bitumen fumes or dermal exposure to bitumens. Bitumens are chemically different from many carcinogenic coal-tar based materials. Both have been employed in road paving and waterproofing. We examined and combined the results of the epidemiologic studies conducted on asphalt workers and roofers. We examined the cancer risk separately in three broad job categories: 1) roofers (exposed to bitumen fumes and previously often to coal-tar fumes); 2) highway maintenance workers (HMWs) and road pavers (exposed to bitumen fumes as well as possibly coal-tar fumes previously); and 3) miscellaneous and unspecified bitumen/asphalt workers. In roofers, an increased risk was suggested for cancers of the lung (aggregated relative risk 1.8, 95% confidence interval 1.5-2.1), stomach (1.7, 1.1-2.5), nonmelanoma skin (4.0, 0.8-12), and leukemia (1.7, 0.9-2.9). Some of the excesses may be attributable to polycyclic aromatic hydrocarbons (PAH) from coal-tar products. The aggregated relative risks in road pavers and HMWs were consistently lower than in roofers for cancers of the lung (0.9, 0.8-1.0), stomach (1.1, 0.8-1.5), bladder (1.2, 0.7-1.8), skin (2.2, 1.2-3.7), and leukemias (1.3, 0.9-1.8). Their risk of skin cancer was significantly increased, based on one study. Miscellaneous and unspecified workers had a significant excess (1.5, 1.2-1.8) of lung cancer. The data were poorly focused to address the carcinogenicity of bitumen fumes, as contrasted with tar-derived exposures. For the prospect of shedding more light on the bitumen-cancer controversy, the feasibility of a powerful multicenter cohort is currently being studied by the International Agency for Research on Cancer (IARC).

Journal Article
TL;DR: In this paper, age-specific data from six cancer registries (three in Asia, three in Latin America) and national mortality datasets from Central and South America (three), the Caribbean (two), Asia (two) and Mauritius (two).
Abstract: The developing countries are represented by incidence and mortality datasets from 16 populations. Trends are studied using age specific data from six cancer registries (three in Asia, three in Latin America) and national mortality datasets from Central and South America (three), the Caribbean (two), Asia (two) and Mauritius. In Africa, three cancer registries (in Nigeria, Uganda and Zimbabwe) provide time series of 15 years or more. Systematic examination of time trends is confined to five major sites (stomach, lung, breast, cervix uteri and colon-rectum), with a comment on observed trends in the other important cancers of developing countries (mouth/pharynx, oesophagus and liver). Although uniformity is not to be expected in such diverse material, some overall patterns emerge. Stomach cancer, as in the developed world, appears to be declining in importance. Lung cancer rates are rising, although in males, the increases are most marked in the elderly, with more recent birth cohorts in several populations showing a decline in risk. Breast cancer incidence and mortality rates are rising in most populations, with changes usually more marked in younger women. Conversely, cervix cancer, at present the most common cancer of women in developing countries, shows declines in incidence and mortality in the majority of populations studied, although Africa is clearly an exception. Cancer of the large bowel is becoming more frequent, although there are exceptions (eg Bombay, Mauritius and Trinidad). In the highest risk population (Uruguay), mortality seems to have peaked around 1965 and has since declined.

Journal ArticleDOI
TL;DR: In this article, the formation, detection, and role in carcinogenesis of Ethenobases in Dna were discussed. But they did not consider the role of the Etheno-cell.
Abstract: (1994). Formation, Detection, and Role In Carcinogenesis of Ethenobases in Dna. Drug Metabolism Reviews: Vol. 26, No. 1-2, pp. 349-371.

Journal Article
TL;DR: The results suggest that genomic instability revealed by (CA)n repeat changes does not seem to contribute to induction of point mutations in p53 or connexin 32 genes but may participate in loss of heterozygosity at APC/MCC loci.
Abstract: We have examined whether alterations of simple (CA)n DNA repeats, as observed in human colon cancers, occur during human gastric carcinogenesis and whether such alterations reflect genomic instability that could lead to other genetic changes. A total of 22 gastric cancer samples were analyzed: 15 well or moderately differentiated adenocarcinomas, 6 signet-ring cell carcinomas, and 1 poorly differentiated adenocarcinoma. When (CA)n repeat sequences were examined at 10 loci, one adenocarcinoma showed a loss of repeat sequences at five loci, three adenocarcinomas gained a repeat at one locus, and one adenocarcinoma had new, repeated sequences at five loci. Three samples showed mutations in the p53 gene, two in exon 5 (both GC to AT transition at a CpG dinucleotide) and one in exon 7 (AT to GC transition). Only one sample with a p53 mutation also showed altered (CA)n repeats. A putative tumor suppressor gene, connexin 32, was not altered as assessed by single-strand conformation polymorphism analysis. These results suggest that genomic instability revealed by (CA)n repeat changes does not seem to contribute to induction of point mutations in p53 or connexin 32 genes but may participate in loss of heterozygosity at APC/MCC loci. The results are consistent with the hypothesis that different mechanisms are involved in the gain and loss of (CA)n repeats.

Journal ArticleDOI
TL;DR: Differences in total incidence or in relative frequencies of particular histological types between Western countries and Japan and between ethnic groups in the US suggest a substantial contribution of genetic predisposition in their aetiology.
Abstract: Background Intracranial and spinal cord tumours are the second most frequent type of childhood cancer after leukaemia, accounting for around 20% of cases in many regions of the world, yet there have been few studies of their incidence by histological type and subsite. Methods Age-specific and age-adjusted incidence rates were calculated from data in the study, 'International Incidence of Childhood Cancer', co-ordinated by the International Agency for Research on Cancer. Results The highest age-adjusted incidence, 31.4 per million, was observed in the Nordic countries, and rates between 24 and 27 per million were found in most other predominantly white Caucasian populations. In the US, black children had a significantly lower incidence (21.7) than whites (26.4). Lower rates were seen in South America, Africa and Asia, the lowest being those for Chinese populations, and for blacks in Africa, both below 15 per million. Among white populations, astrocytomas were the commonest histological type, often with an incidence of at least 10 per million, followed by medulloblastomas, 5-6 per million, and ependymomas, 2-4 per million. In other regions with lower incidence rates, these three types accounted for similar proportions of the total. Black children in the US had a higher incidence of craniopharyngiomas than whites and there was an unusually high incidence of pineal tumours in Japan, 0.9 per million compared with 0.3-0.4 in many other countries. Conclusions The low recorded total incidence in developing countries may be partly due to underascertainment. Differences in total incidence or in relative frequencies of particular histological types between Western countries and Japan and between ethnic groups in the US suggest a substantial contribution of genetic predisposition in their aetiology.

Journal ArticleDOI
TL;DR: The authors found no meaningful differences in the effect of most of the nutrients between intestinal and diffuse cancers, consistent with previously reported results about the protective effect of fruit and vegetables and the increased risk associated with foods that are important sources of nitrites and preformed nitrosamines.
Abstract: A case-control study on diet and gastric cancer, carried out in selected areas of four regions of Spain (Aragon, Castile, Catalonia, and Galicia) in 1988 and 1989, included 354 cases of histologically confirmed gastric adenocarcinoma and 354 controls matched by age, sex, and area of residence. Cases and controls were selected from 15 hospitals, representing most of the hospital facilities in the study areas. Usual diet was estimated by means of a dietary history questionnaire administered by interview. An increased risk of gastric cancer was observed for high consumption of exogenous nitrosamines (odds ratio = 2.1 for the highest quartile of consumption versus the lowest; p for linear trend = 0.007), nitrites, fat, and cholesterol. However, in a multivariate regression model, the effect of fat and cholesterol disappeared. An inverse association with the risk for gastric cancer was seen for high intake of fiber, vitamin C, folate, carotene, and nitrates. High consumption of vitamin C seemed to neutralize the increased risk related to simultaneous consumption of nitrosamines. For histologic type, the authors found no meaningful differences in the effect of most of the nutrients between intestinal and diffuse cancers. Their findings are consistent with previously reported results about the protective effect of fruit and vegetables and the increased risk associated with foods that are important sources of nitrites and preformed nitrosamines.

Journal ArticleDOI
TL;DR: It is concluded that this short segment of the Dsg1 tail provides a plakoglobin-binding site and is important for plaque assembly and the specific anchorage of either actin filaments in adherens junctions or IFs in desmosomes.
Abstract: The carboxyterminal cytoplasmic portions (tails) of desmosomal cadherins of both the desmoglein (Dsg) and desmocollin type are integral components of the desmosomal plaque and are involved in desmosome assembly and the anchorage of intermediate-sized filaments. When additional Dsg tails were introduced by cDNA transfection into cultured human epithelial cells, in the form of chimeras with the aminoterminal membrane insertion domain of rat connexin32 (Co32), the resulting stably transfected cells showed a dominant-negative defect specific for desmosomal junctions: despite the continual presence of all desmosomal proteins, the endogenous desmosomes disappeared and the formation of Co32-Dsg chimeric gap junctions was inhibited. Using cell transfection in combination with immunoprecipitation techniques, we have examined a series of deletion mutants of the Dsg1 tail in Co32-Dsg chimeras. We show that upon removal of the last 262 amino acids the truncated Dsg tail still effects the binding of plakoglobin but not of detectable amounts of any catenin and induces the dominant-negative phenotype. However, further truncation or excision of the next 41 amino acids, which correspond to the highly conserved carboxyterminus of the C-domain in other cadherins, abolishes plakoglobin binding and allows desmosomes to reform. Therefore, we conclude that this short segment provides a plakoglobin-binding site and is important for plaque assembly and the specific anchorage of either actin filaments in adherens junctions or IFs in desmosomes.

Journal ArticleDOI
TL;DR: A sensitive and specific method has been developed to measure levels of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine adducted to DNA in tissues and provided evidence for PhIP-DNA adducts in two of the colon samples, but not in the samples from human pancreas or urinary bladder.
Abstract: A sensitive and specific method has been developed to measure levels of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) adducted to DNA in tissues. The method is based on alkaline hydrolysis of PhIP from DNA, followed by organic solvent extraction, derivatization to form the electron-capturing bis(pentafluorobenzyl) derivative, and analysis by gas chromatography/electron capture mass spectrometry (GC/MS) using a deuterium-labeled internal standard. The method can detect PhIP-DNA adducts at levels down to 0.03 fmol of PhIP/micrograms of DNA (1 PhIP adduct/10(8) normal nucleotides) for a 100 micrograms sample of DNA. The method is reproducible for sample sizes ranging up to at least 1000 micrograms of DNA. A series of 20 DNA samples from 5 tissues of rats treated with a single oral dose of PhIP were analyzed both by alkaline hydrolysis-GC/MS and by 32P-postlabeling. Results from the two methods were highly correlated (r2 = 0.83), with adduct levels determined by alkaline hydrolysis-GC/MS averaging about 60% of the levels determined by 32P-postlabeling. A pilot survey of 24 individual human tissue DNA samples, including pancreas (n = 12), colon mucosa (n = 6), and urinary bladder epithelium (n = 6), was carried out by alkaline hydrolysis-GC/MS and 32P-postlabeling. Both methods provided evidence for PhIP-DNA adducts in two of the colon samples, but not in the samples from human pancreas or urinary bladder.

Journal ArticleDOI
01 Apr 1994-Gut
TL;DR: It is concluded that omeprazole (20 mg once daily for two weeks in healthy volunteers is associated with gastric bacterial proliferation but does not increase concentrations of N-nitroso compounds.
Abstract: Previous studies have suggested that profound inhibition of gastric acid secretion may increase exposure to potentially carcinogenic N-nitroso compounds. The aim of this study was to find out if the proton pump inhibitor omeprazole (20 mg daily) is associated with increased concentrations of potentially carcinogenic N-nitroso compounds in gastric juice. The volume of gastric contents, number of bacteria, and concentrations of nitrates, nitrites, and N-nitroso compounds was determined in gastric aspirates obtained after an overnight fast in 14 healthy volunteers (7M:7F) after one week of treatment with placebo, and one and two weeks' treatment with omeprazole. Median bacterial concentrations were 1.0 x 10(4) (range 5.0 x 10(3)-5.0 x 10(6)) colony forming units (CFU)/ml after one weeks' treatment with placebo and increased significantly to 4.0 x 10(5) (0-3.3 x 10(7)) CFU/ml after two weeks' treatment with omeprazole (p < 0.05). A similar increase was seen in the concentration of nitrate reducing bacteria. There was no difference in the volume of gastric aspirates after treatment with omeprazole when compared with placebo (65 (29-155) ml v 42 (19-194) ml). The concentration of N-nitroso compounds was 0.13 (0-1.0) mumol/l after two weeks of omeprazole, which was not significantly different from that seen with placebo (0.15 (0-0.61) mumol/l). There was also no increase in the concentrations of nitrates or nitrites. It is concluded that omeprazole (20 mg once daily) for two weeks in healthy volunteers is associated with gastric bacterial proliferation but does not increase concentrations of N-nitroso compounds.

Journal ArticleDOI
TL;DR: These findings could be interpreted as indicating that past infections with HSV‐2, N. gonorrhoeae and C. trachomatis are surrogate markers of HPV, but because HPV DNA may have escaped detection, it cannot exclude that these STAs are also of separate etiologic significance.
Abstract: Case-control studies of cervical intra-epithelial neoplasia grade III (CIN III) and of invasive cervical cancer were carried out in Spain and Colombia to assess the relationship between cervical cancer and 6 common sexually transmitted agents (STAs). The CIN-III studies included 525 cases and 512 controls matched for age and for the place of recruitment; the invasive-cancer studies included 373 histologically confirmed cases of squamous-cell carcinoma and 387 age-stratified controls selected randomly from the populations that generated the cases. Antibodies to Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, herpes simplex virus type II (HSV-2) and cytomegalovirus (CMV) were tested in 88% of the women. Cervical scrapes were examined for HPV DNA in 63% of the women using a polymerase-chain-reaction assay (PCR). Among controls, the highest antibody prevalence was to CMV (96.5%), followed by HSV-2 (31.4%) and C. trachomatis (23.3%). For all STAs, the sero-prevalence was markedly higher in Colombia than in Spain both for cases and for controls. After adjustment for the presence of HPV DNA, C. trachomatis was the only STA associated with CIN III in both countries; Spain and Colombia. In both countries, the risk of CIN III increased with increasing of C. trachomatis antibody titers. Among Spanish women, an increase in risk of invasive carcinoma was found for those with antibodies to N. gonorrhoeae; those with antibodies to HSV-2 and those with antibodies to C. trachomatis. These associations were present only in HPV-DNA-negative women. Among HPV-DNA-positive women, none of the STAs considered were associated with cervical neoplasia. Our findings could be interpreted as indicating that past infections with HSV-2, N. gonorrhoeae and C. trachomatis are surrogate markers of HPV, but because HPV DNA may have escaped detection, we cannot exclude that these STAs are also of separate etiological significance.

Journal ArticleDOI
TL;DR: Ability to tan and propensity to burn were also associated with number of nevi, although not in a simple fashion; numbers of neVI were highest in intermediate categories of these two variables.
Abstract: A survey of benign melanocytic nevi was conducted among schoolchildren in Perth, Western Australia, in 1985, with the aim of describing the prevalence and causes of nevi. Children were recruited from Perth public schools that were chosen to be representative of the socioeconomic and geographic distribution of the population. Of 4,898 eligible children, 2,595 (53%) had all of their nevi counted by one member of a team of five nurses. Analysis was restricted to 2,552 children aged 5-14 years. Children of European origin (i.e., white children), who comprised the majority of the sample (2,376 children), had many more nevi than did children of other ethnic origins. Among white children, the prevalence of nevi increased progressively with age, although the number of nevi per unit of skin area reached a plateau at about 9 years of age. Boys had more nevi at all ages than did girls. The number of nevi per unit of area was highest on the lateral surfaces of the upper limbs and the face and neck, and was lowest on the lower limbs. Children whose parents had been born in Southern Europe were likely to have few nevi. Children with red hair had relatively few nevi, but children with light skin generally had more nevi than children with darker skin. Ability to tan and propensity to burn were also associated with number of nevi, although not in a simple fashion; numbers of nevi were highest in intermediate categories of these two variables. The relation with freckling was also complex; the mean number of nevi increased with increasing freckling until the freckling became moderate to heavy, after which it fell.

Journal ArticleDOI
TL;DR: The epidemiologic evidence from studies of insulation workers with high exposures suggests an interaction that approximates the multiplicative model, indicating that each of the two factors has an independent action on the multistage process of carcinogenesis.
Abstract: The joint effects of exposure to two known lung carcinogens, tobacco smoking and asbestos, are reviewed. The variable pattern of interaction--ranging from supramultiplicative to less than additive--may reflect the fact that both asbestos and smoking are complex carcinogens which can affect more than one stage of lung carcinogenesis. The joint effect of two such agents will depend on the relative magnitude of the effects at each stage. The epidemiologic evidence from studies of insulation workers with high exposures suggests an interaction that approximates the multiplicative model, indicating that each of the two factors has an independent action on the multistage process of carcinogenesis. Very limited information is available on the interaction between these two agents in causing specific histological types of lung cancer. Both tobacco smoke and asbestos fibers can be genotoxic and cytotoxic and cause proliferative lesions in the lungs. Tobacco smoke is known to contain carcinogens that bind to critical genes in DNA (deoxyribonucleic acid) and cause mutations. Asbestos fibers may cause chronic inflammation of the lungs, which releases various cytokines and growth factors, and therefore may provide a possible selective growth advantage for mutated cells.

Journal ArticleDOI
TL;DR: Although direct sequencing of RET exons 10 and 11 allows the identification of a constitutional mutation in a large proportion of MEN 2A and FMTC families, the data sustain the existence of other MTC predisposing mutations elsewhere in RET coding or regulating region.
Abstract: Constitutional mutations of the RET proto-oncogene have been identified in multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC) families. We sequenced RET exons 10 and 11 in 86 unrelated patients with an inherited predisposition to MTC (excluding MEN 2B). Germ-line mutations were identified in 93% of the MEN 2A families and 67% of the FMTC families tested. All were missense mutations affecting one of three cysteines in the extracellular domain of the RET tyrosine kinase receptor. The prevalence of phaeochromocytoma and hyperparathyroidism was significantly higher in families with a mutation of cysteine 634. These data confirm the preferential localisation of MEN 2A and FMTC associated mutations and the strong correlation between clinical manifestations and the position of RET mutation. Although direct sequencing of RET exons 10 and 11 allows the identification of a constitutional mutation in a large proportion of MEN 2A and FMTC families, our data sustain the existence of other MTC predisposing mutations elsewhere in RET coding or regulating region.

Journal ArticleDOI
TL;DR: The increasing challenge for the control of cancer in developing countries is outlined and the number of new cases of cancer is expected to increasedramatically.
Abstract: Cancer is a major cause of mortality in developing countries, accounting for 13 percent of the annual deaths in adults. As the population increases and ages, the number of new cases of cancer is expected to increase dramatically. This article presents epidemiologic information on the principal cancers in developing countries and outlines the increasing challenge for the control of cancer in developing countries.

Journal ArticleDOI
TL;DR: Hormonal factors such as oral contraceptives and high parity appear to confer an additional risk increasing the progression from chronic HPV infection to cancer, indicating that HPV is the main cause of cervical cancer in two countries with contrasting rates of cervicalcancer.
Abstract: To assess the association between human papillomavirus (HPV) and cervical cancer we have carried out two case-control studies of cervical intraepithelial neoplasia grade III (CIN III) (525 cases and 512 matched controls) and two case-control studies of invasive squamous cell carcinoma (436 cases and 387 population controls) in Cali, Colombia and nine provinces of Spain. HPV DNA detected by polymerase chain reaction, a PCR-based hybridization assay in the exfoliated cells of the uterine cervix, was the strongest risk factor in both countries. For invasive cancer the adjusted odds ratios and 95% confidence intervals were: 46.2 (18.5-115.1) in Spain and 15.6 (6.9-34.7) in Columbia and for CIN III they were: 56.9 (24.8-130.6) in Spain and 15.5 (8.2-29.4) in Columbia. This strong association was specific for types 16, 18, 31, 33 and 35 and also for HPV types not yet characterized. Hormonal factors such as oral contraceptives and high parity appear to confer an additional risk increasing the progression from chronic HPV infection to cancer. Our overall results indicate that HPV is the main cause of cervical cancer in two countries with contrasting rates of cervical cancer, Columbia having an incidence rate about 8 times higher than Spain.

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TL;DR: Tumours reported at increased incidence, in particular among Hodgkin's disease patients, for whom a carcinogenic effect of chemotherapy seems plausible, are non-Hodgkin's lymphoma and lung cancer.
Abstract: Many agents used in cancer chemotherapy are known carcinogens. However, few secondary malignancies have been definitely linked to chemotherapy, since studies on this problem are complicated by meth...

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TL;DR: Linkage analysis shows that the EPPK locus lies on the long arm of chromosome 17 near the type I keratin gene cluster and the proposed breast cancer gene (BRCA1), and a single base mutation within the rod domain of the protein cosegregates with E PPK.
Abstract: Epidermolytic palmoplantar keratosis (EPPK) cosegregates with breast and ovarian cancers in a large French pedigree, raising the possibility that a single genetic mutation might cause these conditions and offering a potential lead to the identification of a hereditary breast/ovarian cancer gene. We have performed linkage analysis and show that the EPPK locus lies on the long arm of chromosome 17 near the type I keratin gene cluster and the proposed breast cancer gene (BRCA1). The type I keratin 9 gene has been partially sequenced in four affected individuals. A single base mutation within the rod domain of the protein cosegregates with EPPK in all affected individuals tested. Although inheritance of this mutation is likely responsible for EPPK, it is unlikely to be the cause of the breast and ovarian cancer.

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TL;DR: Mortality from neoplasms of the lymphatic and hematopoietic tissues increased with time since first exposure and average level of exposure to styrene, but was not consistently associated with duration of exposure or with cumulative exposure.
Abstract: OBJECTIVES-The goal of this study was to determine whether exposure to styrene is associated with an increased risk for neoplasms of the lymphatic and hematopoietic tissues. METHODS-A historical cohort study was conducted in Denmark, Finland, Italy, Norway, Sweden, and the United Kingdom. It involved 40 688 workers ever employed in the reinforced plastics industry, where high exposure to styrene occurs. Exposure to styrene was reconstructed through job histories and environmental and biological monitoring data. Cause-specific national death rates were used as the reference. Poisson regression was applied for internal comparisons. RESULTS-Among the exposed workers, no excess was observed for mortality from all neoplasms. Mortality from neoplasms of the lymphatic and hematopoietic tissues increased with time since first exposure and average level of exposure to styrene, but was not consistently associated with duration of exposure or with cumulative exposure. CONCLUSIONS-These findings leave open the possibility of an excess risk of neoplasms of the lymphatic and hematopoietic tissues among workers exposed to styrene.

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TL;DR: Results show that expression of specific cytochrome P450s is altered in association with overexpression of HBV large envelope protein and liver injury in this model, which may have general relevance to human HCC, the etiology of which is associated with a diverse range of liver‐damaging agents.
Abstract: The relative roles of hepatitis B virus (HBV) and aflatoxn and their possible mechanism of interaction in the etiopathogenesis of hepatocellular carcinoma (HCC) are not understood. One hypothesis is that viral infection and associated liver injury alter expression of carcinogen-metabolizing enzymes. We tested this hypothesis in an HBV-transgenic mouse model in which a synergistic interaction occurs between aflatoxin B1 (AFB1) and HBV in the induction of HCC (Sell et al., Cancer Res 51:1278–1285, 1991). In this transgenic mouse lineage, overproduction of the HBV large envelope protein results in progressive liver cell injury, inflammation, and regenerative hyperplasia. Initially, two cytochrome P450s of importance in AFB1 metabolism in the mice were identified, namely Cyp2a-5 and Cyp3a, using specific antibodies and chemical inhibitors. The expression of these P450 isoenzymes and an α-class glutathione S-transferase (GST) isoenzyme, YaYa, were examined. Increased expression and altered distribution of Cyp2a-5 were demonstrated, by immunohistochemical analysis, to be associated with the development of liver injury in mice and to increase with age between 1 and 12 months. Cyp3a expression was also increased in HBV-transgenic mice, but the increase was not as clearly related to age. GST YaYa levels were the same in HBV-transgenic mice and their nontransgenic littermates of all ages. These results show that expression of specific cytochrome P450s is altered in association with overexpression of HBV large envelope protein and liver injury in this model. This may have general relevance to human HCC, the etiology of which is associated with a diverse range of liver-damaging agents.