Showing papers by "International Agency for Research on Cancer published in 1993"

Estimates of the worldwide incidence of eighteen major cancers in 1985.

Abstract: The annual incidence rates (crude and age-standardized) and numbers of new cases of 18 different cancers have been estimated for the year 1985 in 24 areas of the world. The total number of new cancer cases (excluding non-melanoma skin cancer) was 7.6 million, 52% of which occur in developing countries. The most common cancer in the world today is lung cancer, accounting for 17.6% of cancers of men worldwide, and 22% of cancers in men in the developed countries. Stomach cancer is now second in frequency (it was slightly more common than lung cancer in 1980) and breast cancer—by far the most important cancer of women (19.1% of the total)—is third. There are very large differences in the relative importance of the different cancers by world area. The major cancers of developed countries (other than the 3 already named) are cancers of the colon-rectum and prostate, and, in developing countries, cancers of the cervix uteri, mouth and pharynx, liver and oesophagus. The implications of these patterns for cancer control, and specifically prevention, are discussed. Tobacco smoking and chewing are almost certainly the major prevent able causes of cancer today.

Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2

Abstract: Neurofibromatosis type 2 (NF2) is a monogenic dominantly inherited disease predisposing carriers to develop nervous system tumours. To identify the genetic defect, the region between two flanking polymorphic markers on chromosome 22 was cloned and several genes identified. One is the site of germ-line mutations in NF2 patients and of somatic mutations in NF2-related tumours. Its deduced product has homology with proteins at the plasma membrane and cytoskeleton interface, a previously unknown site of action of tumour suppressor genes in humans.

Estimates of the worldwide mortality from eighteen major cancers in 1985. Implications for prevention and projections of future burden

Abstract: This report presents worldwide estimates of annual mortality from all cancers and for 18 specific cancer sites around 1985. Crude and age-standardized mortality rates and numbers of deaths were computed for 24 geographical areas. Of the estimated 5 million deaths from cancer (excluding non-melanoma skin cancer), 56% occurred in developing countries. The most frequent neoplasm is lung cancer, accounting for 22% of cancer deaths in men. Among women breast cancer is the leading malignancy, accounting for 16% and 11% of all cancer deaths in developed and developing countries, respectively. In developing countries, cancer of the cervix uteri ranks first, breast cancer second. The second most frequent cause of death from cancer in both sexes is cancer of the stomach, followed by liver cancer in men and by colon/rectum cancer in women. Cancers of the colon/rectum and prostate maintain a high rank in men living in developed countries, while cancers of the lung, ovary and pancreas occupy similar ranks among women. In developing countries, cancers of the oesophagus and mouth/pharynx follow those previously mentioned in both sexes. If the estimated rates continue to prevail, increases in the numbers of deaths of 20.4% in developed and 18.1% in developing countries are expected by the year 2000, simply as a consequence of demographic trends towards ageing and population growth. Our results provide an indication of the potential impact of preventive practices. It is estimated that 20% of all cancer deaths (1 million) could be prevented by eliminating tobacco smoking. Mortality from cancers of the liver and uterine cervix, both major problems in developing countries, could be substantially reduced by immunization against hepatitis B virus infection and early detection through Pap smears, respectively.

How much melanoma is caused by sun exposure

Abstract: Estimates have been made of the proportion of cutaneous malignant melanomas caused by sun exposure by comparing the observed incidence of melanoma with estimates of the incidence in the absence of sun exposure. The estimated proportions varied from 0.97 in males and 0.96 in females in Queensland, Australia, when the incidence on the whole body was compared with that on unexposed sites, to 0.68 when incidence in people born in Australia was compared with that in migrants to Australia from areas of lower sun exposure. A comparison of US Whites and US Blacks, in which the incidence in Blacks was taken as the incidence in unexposed Whites, gave estimates of 0.96 in males and 0.92 in females. It was estimated that some 59,000 (65%) of about 92,000 melanomas that occurred worldwide in 1985 were caused by sun exposure. This is probably a minimum estimate. That 20% of the world's melanomas are estimated to occur in Black African and Asian populations and are of unknown cause would justify studies of the causes of melanoma in these populations.

Tobacco smoking, alcohol drinking, and cancer of the oral cavity and oropharynx among U.S. veterans.

Abstract: Background. Independent carcinogenic effects of alcohol drinking and tobacco smoking as well as their interaction can be usefully studied in a population of heavy drinkers and smokers. Methods. A hospital-based case-control study was conducted during 1972 to 1983 in a large Veterans hospital in East Orange, New Jersey. A total of 359 oral cavity-oropharynx cancer cases and 2280 controls were interviewed according to tobacco smoking, use of smokeless tobacco, alcoholic beverage, coffee and tea drinking, race, family origin, religion, and occupation as bartender. Results. Odds ratio of oral cancer increased up to the level of 35 cigarettes per day and 21 whiskey equivalents per day: no further increase was found for higher level of exposure to either factor. A protective effect of quitting smoking was found, but the number of former smokers was small. No difference occurred in oral cancer risk according to type of alcoholic beverage drunk. An interaction effect compatible with a multiplicative model was found between the two exposures. Blacks were at lower risk than whites, and, in the latter group, individuals of Italian origin were at lower risk than individuals from northern or central European countries. Conclusions. Alcohol drinking and tobacco smoking were responsible for the majority of oral cancer cases in this population of US Veterans.

Review article: Epidemiology of male breast cancer. A meta‐analysis of published case‐control studies and discussion of selected aetiological factors

Abstract: Male breast cancer is a rare tumour in all parts of the world. About 1% of all breast cancers occur in men, but the male/female ratio is higher among black than among white populations. This effect can be seen in US cancer registries and even more markedly in African data. A positive correlation exists on a population scale between male breast cancer and prostate cancer. Seven case-control studies of male breast cancer are available, and a pooled analysis was conducted of the most commonly suspected risk factors. Male breast cancer appears to be associated with marital status: Mantel-Haenszel exposure odds ratio (EOR) for never married = 1.6; 95% confidence limits (CL) = 1.1, 2.3, religion (EOR for being Jewish = 2.1; 95% CL = 1.4, 3.2), previous breast pathology (EOR for positive history of benign breast disease = 2.7; 95% CL = 1.7, 4.2), gynaecomastia (EOR for positive history = 6.2, 95% CL = 3.4, 11.4), previous testicular pathology (EOR for positive history = 2.2; 95% CL = 1.5, 3.3), previous liver diseases (EOR for positive history = 1.6; 95% CL = 1.0, 2.4) and family history of breast cancer (EOR for first-degree relative with breast cancer = 2.5; 95% CL = 1.7, 3.7). No association is found with smoking history. Other potential risk factors such as reproductive history, education, occupation, anthropometric variables, association with various diseases, and specific exposures such as drug use, were not systematically evaluated in all studies and provide sometimes contradictory results, possibly due to small numbers of exposed subjects. Overall, the analytical epidemiology of male breast cancer presents similarities with the epidemiology of female breast cancer, with a potential role of factors related to hormonal status, relative hyperoestrogeny in men being potentially linked to increased risk of disease. Genetics may also play a role, with high risk linked to a familial history of breast cancer, and with a major risk in patients with Klinefelter's syndrome.

The GSTM1 null genotype as a potential risk modifier for squamous cell carcinoma of the lung

Abstract: The identification of genetic traits that predispose individuals to environmentally induced cancers is one of the challenges in the assessment of individual cancer risk. For this reason, individual variations in the expression of enzymes involved in biotransformation reactions have been extensively studied. One such polymorphic enzyme is GSTM1, which belongs to the class Mu of glutathione S-transferases (GSTs), and is only expressed in 55-60% of Caucasians. Previous data suggest that smokers lacking GSTM1 activity may be at greater risk of developing lung cancer. In this study, we used a polymerase chain reaction-based method to examine this issue in a Finnish study population. We found that 44% of a control group of 142 individuals lacked the GSTM1 gene, i.e. they had the GSTM1 null genotype; the rest were either homozygous or heterozygous for the expressed GSTM1 alleles. In a group of 36 patients with non-neoplastic pulmonary diseases, an identical distribution was observed. However, among 138 lung cancer patients the distribution of the GSTM1 genotypes deviated from that found in the healthy controls (53% nulled; odds ratio 1.5, 95% confidence interval 0.9-2.3). Furthermore, when the lung cancer patients were analysed by tumour type, a statistically significant increase in the GSTM1 null genotypes (62%; n = 71) was seen in the squamous cell carcinoma group, with an odds ratio of 2.1 (95% confidence interval 1.2-3.8). These data support the suggestion that GSTM1 null genotype may act as a risk modifier in lung cancer.

Cholangiocarcinoma: epidemiology, mechanisms of carcinogenesis and prevention.

Abstract: Cholangiocarcinoma is a relatively rare cancer; worldwide it accounts for an estimated 15% of liver cancers. In most areas, the etiology is rather obscure, and identified risk factors such as hepatolithiasis, inflammatory bowel disease, and exposure to Thorotrast can account for only a small proportion of cases. In certain areas of southeast and eastern Asia, however, incidence rates are very high, and here there is a strong association with infection with the liver flukes Clonorchis sinensis and Opisthorchis viverrini. The mechanisms of carcinogenesis in O. viverrini infection have been the subject of considerable research; it seems that the presence of parasites induces DNA damage and mutations as a consequence of the formation of carcinogens/free radicals and of cellular proliferation of the intrahepatic bile duct epithelium. Preventive strategies in areas endemic for liver flukes appear straightforward, but breaking the cycle of infection has proved difficult in practice.

Diet and colorectal adenomas: a case-control study in Majorca.

Abstract: A case-control study on dietary factors and colorectal adenomas was conducted in the island of Majorca, Spain, from April 1987 to February 1990 Subjects were interviewed using a food frequency questionnaire Nutrient and caloric intake was estimated using local food composition tables The risk of colorectal adenomas was related to the consumption of sugar and pastries Consumption of vegetables was highly protective, irrespective of the cooking procedures Analyses by nutrients identified as protective factors fiber from fruits and vegetables, magnesium and zinc, and vitamins C, B 6 and folic acid No excess risk was found for alcohol drinking, intake of saturated fats or animal protein Of the non-dietary factors, sedentariness in the work-place and urban residence were the only risk factors identified

High variability of nitrosamine metabolism among individuals: Role of cytochromes P450 2A6 and 2E1 in the dealkylation of N-nitrosodimethylamine and N-nitrosodiethylamine in mice and humans

Abstract: We undertook this study to answer several questions regarding nitrosamine metabolism. Kinetics of nitrosamine metabolism showed the involvement of at least two enzymes in the dealkylation of N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) in mouse liver microsomes. Coumarin inhibited both reactions competitively. On the other hand, microsomal coumarin 7-hydroxylase was inhibited by NDMA (Ki 2.7 mM) and NDEA (Ki 0.013 mM). The big difference in the Ki values suggests a higher affinity of NDEA than NDMA to Cyp2a-5 (mouse cytochrome P450coh). A specific antibody against Cyp2a-5 inhibited more of the microsomal NDEA (up to 90%) than NDMA (up to 40%) dealkylation. The converse was true with anti-Cyp2e-1 antibody. These results suggest that the primary substrate for Cyp2a-5 is NDEA and for Cyp2e-1, NDMA. Western blot analysis of human liver microsomes showed a great interindividual variation in the amounts of CYP2A6 (human cytochrome P450coh) and CYP2E1. Also, coumarin 7-hydroxylation and nitrosamine dealkylation varied greatly among individuals. A high correlation (r = 0.93, P < 0.001) was found between NDEA and coumarin metabolism. Both activities were associated with CYP2A6. On the other hand, little or no correlation was found between microsomal CYP2A6 and CYP2E1 or between CYP2E1 and NDEA dealkylation. Immunoinhibition of human microsomal NDEA metabolism by CYP2a-5 antibody varied greatly among individuals (10-90%), suggesting, as in the case of mice, that NDEA is metabolized primarily by CYP2A6, at least in some individuals. Taken together the data suggest that (1) the metabolic activation of nitrosamines in humans varies greatly among individuals; (2) different nitrosamines may partially be metabolized by different cytochrome P450 isozymes; and (3) because of similarities between nitrosamine metabolism in mice and humans, inbred strains of mice would be relevant experimental models for studying nitrosamine activation.

K-ras mutations in human adenocarcinoma of the lung: association with smoking and occupational exposure to asbestos.

Abstract: We investigated point mutational activation of the ras genes (K-ras codons 12, 13 and 61; N-ras codons 12, 13 and 61; H-ras codons 12 and 61) in primary, resected lung cancer by dot blotting and oligonucleotide hybridization. K-ras mutations were found in 14 (29%) of the 48 lung tumour specimens examined, but no N-ras or H-ras mutations were found. The highest frequency of K-ras mutation was observed in adenocarcinoma: 12 of the 21 samples studied (57%) had a mutation, which is one of the highest frequencies reported for lung adenocarcinoma. The commonest type of mutation in these lung tumour samples consisted of transversions: we observed 11, of which 8 (57% of all mutations) were G to T transversions. Most of the 48 patients studied had a history of heavy smoking, either with or without evidence of occupational exposure to asbestos. Statistical analysis revealed--in addition to the highly significant association between the adenocarcinoma type of lung cancer and K-ras mutation--a clear association of K-ras mutations with heavy life-time smoking (> or = 50 pack-years of cigarette smoking; odds ratio (OR) 4.9, 90% CI 1.2-19.5, multivariate analysis). In addition, occupational asbestos exposure showed an elevated, but non-significant, OR of 2.2 (90% CI 0.6-8.7) with the presence of K-ras mutation. We conclude that the occurrence of K-ras mutations in adenocarcinoma of the lung is frequent, and that such mutations are associated with heavy life-time exposure to tobacco smoke, possibly in combination with occupational exposure to asbestos fibres.

Indoor Air Pollution and Lung Cancer in Guangzhou, People's Republic of China

Abstract: A case-control study comprising 224 male and 92 female incident lung cancer cases and the same number of individually matched hospital controls was conducted from June 1983 to June 1984 in Guangzhou, People's Republic of China, to evaluate the association between indoor air pollution and lung cancer risk. Guangzhou residents were exposed to several sources of pollution in their homes, most importantly to cooking fumes. Increased risks were found among subjects living in a house without a separate kitchen (the exposure odds ratio was 2.4 (95% confidence interval (CI) 1.4-4.2) for men and 5.9 (95% CI 2.1-16.0) for women). Similarly, living in a house with poor air circulation was associated with an exposure odds ratio of 2.1 (95% CI 1.2-3.8) for men and 3.6 (95% CI 1.4-9.3) for women. A trend in the association between lung cancer risk and factors pertaining to house and kitchen ventilation was observed, and a decreasing risk of lung cancer was observed for several variables indicating better ventilation, even after adjustment for potential confounders such as education, occupation, living area, smoking, and history of chronic respiratory diseases. No statistically significant differences were found between cases and controls for frequency of cooking at home, presence of a chimney in the kitchen, or type of cooking fuel. Smoking was clearly related to risk of lung cancer in both men and women, and among nonsmoking women, exposure to tobacco smoke from their spouses was also associated with an increased risk. These results suggest that, in addition to smoking, indoor air pollution may be a risk factor for lung cancer.

An analysis of a melanoma epidemic

Abstract: Between 1986 and 1988 the annual incidence of invasive melanoma in the Hunter area of New South Wales, Australia, almost doubled to 52.5 per 100,000 in men and 42.9 per 100,000 in women. These rates have been maintained and are similar to those reported for 1987 in Queensland, Australia, which are the highest in the world. Most of the increase in incidence was in melanomas less than 1,50 mm in thickness, and adults of both sexes and all ages were affected. Thicker melanomas also increased in incidence but only in adults 45 years and older, and mainly in men. An analysis of health insurance data on treatment of skin lesions and data from a histopathology laboratory suggested that diagnosis and treatment of skin lesions generally in the Hunter area had increased almost 2-fold over this period. Advancement of the time of diagnosis and a real increase in incidence were likely explanations for some of the observed trends. Increasing diagnosis of a non-metastasising form of thin melanoma, consequent upon increasing removal of pigmented skin lesions by medical practitioners, may also explain some of the observed increase in the incidence of the disease. This possibility has important implications for proposed population screening programs, and methods are needed to distinguish such lesions, if they exist, from potentially fatal melanoma.

International variations in the incidence of childhood bone tumours.

Abstract: Bone cancers comprise about 5% of childhood neoplasms. Osteosarcoma, the most common sub-type, shows a somewhat irregular geographic pattern of incidence, with low rates in some Asian (Indian, Japanese, Chinese) and Latin American populations. Incidence is similar in the sexes and rises steeply with age, accompanied by an increasing proportion of tumours localized in the long bones of the legs. Rates in the USA are higher in blacks than in whites, as a result of a higher incidence at ages 10 to 14 and of tumours of the leg bones. The descriptive epidemiology is consistent with early observations linking risk to the amount of bone growth. Ewing's sarcoma is rare in black populations (USA and Africa) and in eastern Asia. Compared with osteosarcoma, a lower percentage of tumours is localized to the long bones, and incidence rises less steeply with age and is accompanied by an increasing proportion of pelvic tumours. Chondrosarcoma is a rare cancer in children (less than 5% of bone cancers), with an age distribution similar to that of osteosarcoma and a sub-site distribution resembling that of Ewing's sarcoma. Little is known of the aetiology of these tumours; there is clearly a strong genetic predisposition in Ewing's sarcoma but, although the proportion of osteosarcoma cases of genetic origin seems to be small, environmental determinants so far suspected can account for only a small fraction of the total cases.

Human papillomavirus and cervical intraepithelial neoplasia grade III/carcinoma in situ: a case-control study in Spain and Colombia.

Abstract: A case-control study of 525 cases of cervical intraepithelial neoplasia grade III (CIN III) and 512 controls was conducted in Spain and Colombia between 1985 and 1988 to assess the role of human papillomavirus (HPV) in the etiology of CIN III. HPV DNA in cytological scrapes from the cervix was assessed by Virapap and by polymerase chain reaction (PCR) based on the L1 consensus primers. A subsample of 268 specimens was also tested for HPV DNA using Southern hybridization. In Spain, the PCR-based prevalences of HPV DNA were 70.7% among cases and 4.7% among controls. Odds ratio (OR) and 95% confidence interval (numbers in parentheses) for HPV DNA were 56.9 (24.8-130.6). In Columbia HPV DNA was detected by PCR in 63.2% of the cases and in 10.5% of the controls. The OR was 15.5 (8.2-29.4). The estimated fractions of CIN III attributable to HPV were 72.4% in Spain and 60.3% in Colombia. HPV 16 was the predominant viral type and showed the strongest association with CIN III; in Spain the OR was 295.5 (44.8-1946.4) and in Colombia the OR was 27.1 (10.6-69.5). HPV DNA of unknown type was frequent in HPV-positive cases (18.3% in Spain and 38.0% in Colombia) and controls (66.7% in Spain and 47.4% in Colombia). The comparison of results from Virapap and PCR indicated that PCR is the method of choice for epidemiological studies. These data strongly support the hypothesis of the viral origin of CIN III, the common etiology of CIN III and invasive cervical cancer, and the causal nature of the association between HPV and CIN III.

The human CYP2E1 gene and lung cancer : DraI and RsaI restriction fragment length polymorphisms in a finnish study population

Abstract: We investigated point mutational DraI and RsaI restriction fragment length polymorphisms (RFLPs) in the CYP2E1 gene in 101 lung cancer patients, 40 patients with other pulmonary diseases and 121 healthy control subjects. In the DraI RFLP analysis of the 121 healthy control subjects, 96 had the DD genotype, 24 the CD genotype and one the CC genotype. Genotypic distribution in the patients with other pulmonary disease showed a similar trend (P = 0.50), though the group was considerably smaller. The distribution of DraI genotypes in the lung cancer patients was not significantly different from that of the healthy controls (P = 0.44). We were not able to reproduce the results of a Japanese report describing a statistically significant association between the rare DraI RFLP genotype CC and predisposition to lung cancer. Furthermore, this genotype was much less frequent in our study populations than in the Japanese study. The other point mutation studied, which results in RsaI restriction site polymorphism in the 5'-flanking region of the CYP2E1 gene, was almost absent in our study groups. These findings on our Finnish lung cancer population suggest that the CYP2E1 gene polymorphisms studied do not have an important role in susceptibility to lung cancer.

Carcinogenicity of Mercury and Mercury Compounds

Abstract: Mercury and mercury compounds are widely used in modern society, but only sparse data are available on their carcinogenicity Methylmercury chloride causes kidney tumors in male mice Mercury chloride has shown some carcinogenic activity in male rats, but the evidence for female rats and male mice is equivocal Other mercury compounds and metallic mercury have not been tested adequately in experimental animals Epidemiologic data are available for chloralkali workers, dentists and dental nurses, and nuclear weapons workers, three groups occupationally exposed to low levels of mercury and its compounds, but those highly exposed in the past, such as miners, or populations which have suffered massive environmental exposure have not been adequately studied However, the sparse epidemiologic data point toward the possibility of a risk of lung, kidney, and central nervous system tumors Better data are needed on the carcinogenicity of mercury and mercury compounds in humans and experimental animals

Risk factors for cervical intraepithelial neoplasia grade III/carcinoma in situ in Spain and Colombia.

Abstract: A case-control study of 525 histologically confirmed cases of cervical intraepithelial neoplasia grade III and 512 controls was done in Spain and Colombia to assess the role of various risk factors taking into account the effect of human papillomavirus (HPV). The presence of HPV DNA, assessed by a polymerase chain reaction-based method, was the strongest risk factor identified. In Spain the adjusted odds ratio (OR) and 95% confidence interval (CI) (numbers in parentheses) were 56.9 (24.8-130.6) and, in Colombia, were 15.5 (8.2-29.4). In addition to HPV, the multivariate analysis revealed independent effects of early age at first intercourse (in Spain ORa, 4.3; 95% CI, 2.0-9.3 for ages or = 6 versus 1) while number of partners of the woman and specially of her husband showed a strong effect in Spain only (ORa, 6.9; 95% CI, 3.1-15.3 for partners of the husband > or = 21 versus 1-5). Smoking and use of oral contraceptives did not show significant or consistent associations. Among HPV-DNA positive women early age at first intercourse and high parity increased the risk of cervical intraepithelial neoplasia III but the effect was statistically significant only for the former.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary assessment methods evaluated in the Malmö food study

Abstract: A study to evaluate the relative validity of two dietary assessment methods, to be used in a prospective cohort study on diet and cancer, was conducted in a random sample of the Malmo population during 1984-1985. The study compared (i) a long, self-administered «food-use questionnaire» (about 2 50 food items), asking for frequency of consumption of food and beverages and for usual portion size estimated with the help of a booklet of food pictures, and (ii) a combined method involving a shorter food frequency questionnaire (about 130 food items) and a 2-week diet diary, with (iii) a reference method requiring 18 days of weighed food records

DNA Screening for Breast/Ovarian Cancer Susceptibility Based on Linked Markers: A Family Study

Abstract: Background: Linkage to chromosome 17q has been identified in hereditary breast cancer and hereditary breast/ovarian cancer syndrome. A hereditary breast/ovarian cancer syndrome kindred was identified that yielded a highly significant lod score (4.20) when 17q markers were studied, enabling us to identify those who probably carried the cancerassociated gene among the high-risk members of the family. Methods: High-risk members of the hereditary breast/ ovarian cancer syndrome kindred were offered counseling on the basis of 17q markers. Family members responding positively received one-to-one genetic counseling in a structured setting. Subjects were educated before disclosure, and the immediate impact of this information was assessed after disclosure. Results: We provided genetic counseling on the basis of linkage findings to 32 relatives (four men and 28 women). Women who were told they were linkage positive expressed an increased motivation for surveillance and prophylactic surgery. Most women who were told they were linkage negative indicated that they would not proceed with prophylactic surgery but would continue careful surveillance. To date, there has been no evidence of serious emotional disturbances resulting from this disclosure. We believe that this experience can be used by cancer geneticists and physicians in developing protocols for genetic counseling in cancer-associated hereditary disorders. Conclusions: Physicians must understand current developments in cancer genetics and linkage so that they can be applied to genetic counseling and treatment of high-risk patients. (Arch Intern Med. 1993;153:1979-1987)

p53 mutations and aflatoxin B1 exposure in hepatocellular carcinoma patients from thailand

Abstract: The prevalence and type of mutations in the p53 tumour-suppressor gene have been determined in 15 hepatocellular carcinomas (HCC) originating from Thailand. Direct sequencing of exons 5-8 revealed 2 mutations, an AGG to AGT (Arg-->Ser) transversion at codon 249, and an ATC-->AAC (Ile-->Asn) transversion at codon 254. Samples from the Thai patients were analyzed for the presence of aflatoxin-liver DNA and aflatoxin-serum albumin adducts, and all but one were found negative. All the patients were genotyped for glutathione-S-transferase (GST) mu, an enzyme possibly involved in the detoxification of AFB1, and 12 out of 15 had the null genotype. In general, the level of aflatoxin-albumin adducts in sera and the prevalence of p53 mutation at codon 249 in HCC were lower than in other areas at high risk of HCC, including southern China and parts of Africa.

Cigarette smoking, alcohol, tea and coffee consumption and pancreas cancer risk: a case-control study from Opole, Poland.

Abstract: A population-based, case-control study of pancreas cancer was undertaken in Opole, Poland, within the framework of the SEARCH Programme of the International Agency for Research on Cancer: this is the first aetiological study of pancreas cancer reported from Poland where the reported mortality rate has doubled since 1963. This study of pancreas cancer has provided some further supporting evidence of an association between increased pancreas risk with increasing levels of cigarette smoking. The risk rose with increasing lifetime cigarette consumption with a trend which was weakly significant (p = 0.061). Findings regarding lifetime tea and coffee consumption were not consistent with intake of either beverage increasing the risk of this disease. There was a strongly significant trend of decreasing risk with increasing lifetime consumption of tea (p < 0.001), which was also apparent when the analysis was restricted to subjects who were interviewed directly. For coffee consumption, which is low in Poland, there was also a negative association apparent in the data which was not statistically significant among the sub-set of subjects who were directly interviewed. The findings regarding alcoholic beverages were overall null, although the weakly positive trend in risk with spirits consumption (p = 0.71) may deserve further investigation in view of the special nature of the source of spirits (vodka) in Poland.

Geographic association between urinary excretion of N‐nitroso compounds and oesophageal cancer mortality in china

Abstract: Overnight urine samples were collected from approximately 60 male adults in each of 69 counties of China in 1989. Two specimens were collected from each subject--one after a loading dose of proline and ascorbic acid and another after a loading dose of proline only. Levels of N-nitrosamino acids and nitrate were measured in urine samples and correlated with cumulative mortality rates for subjects aged between 0 and 64 years in the 1970s. Oesophageal cancer mortality rates were positively and significantly associated with (i) urinary levels of excreted N-nitrosoproline (NPRO) (after proline and ascorbic acid loading or proline loading only), (ii) N-nitrososarcosine levels, and (iii) nitrosation potential (the decrease in the amount of urinary NPRO after adding ascorbic acid to the proline load). There were also positive correlations between the urinary level of NPRO or other N-nitrosamino acids and that of nitrate. The urinary excretion of nitrate was associated with consumption of various nitrate-rich vegetables. The results suggest that N-nitroso compounds (NOC) or other nitrite-derived carcinogens are implicated in the aetiology of oesophageal cancer in China.

Carcinogenicity of trace elements with reference to evaluations made by the International Agency for Research on Cancer

Abstract: The monograph program of the International Agency for Research of on Cancer has evaluated many trace elements for their carcinogenicity to humans. Five groups of compounds were considered human carcinogens: arsenic and arsenic compounds, beryllium and beryllium compounds, cadmium and cadmium compounds, hexavalent chromium compounds, and nickel compounds. Antimony trioxide, cobalt and cobalt compounds, lead and inorganic lead compounds, methylmercury compounds, and metallic nickel were considered possibly carcinogenic to humans. Antimony trisulfide, trivalent chromium compounds, metallic chromium, ferric oxide, organolead compounds, metallic mercury, inorganic mercury compounds, selenium and selenium compounds, and titanium dioxide were not classifiable. Trace elements studied to a limited extent include copper, manganese, tin, vanadium, and zinc. Among the problems are the lack of relevant data, the definition of active species, the extrapolation of the results of experimental studies to humans, the methodological problems of epidemiologic studies, and the possible anticarcinogenic activity of some trace elements.

Aflatoxin, liver enzymes, and hepatitis B virus infection in Gambian children.

Abstract: The relative contribution of, and possible mechanism of interaction between, aflatoxin and hepatitis B virus (HBV) in the development of primary hepatocellular carcinoma can be better investigated now that markers of individual exposure to both factors are available. In this study, blood samples were collected over a 1-month period from 117 children aged 3 to 4 years, resident in Kuntair or Kerr Cherno in the Upper Niumi District of The Gambia. Samples were analyzed for aflatoxin-albumin (AF-alb) adducts, markers of HBV infection, liver enzymes [serum alanine aminotransferase (ALT)] as markers of liver damage, and glutathione S-transferase M1 genotype. All but two children showed detectable serum AF-alb with levels ranging from 2.2 to 250.4 pg aflatoxin B1-lysine equivalent/mg albumin. There was a significant positive correlation between AF-alb and ALT (r = 0.4; P < 0.001). HBV carriers showed moderately higher levels of AF-alb than noncarriers but the difference was not statistically significant and the association between AF-alb and ALT was unchanged when the HBV carriers were excluded from the analysis, suggesting that factors other than HBV infection contributed to the association. The null glutathione S-transferase M1 genotype was infrequent (17.7%) in this population and was not associated with any difference in AF-alb adduct levels compared to glutathione S-transferase M1-positive individuals. However, the percentage of individuals with the null genotype varied significantly between ethnic groups with 32.1% in Fula, 8.8% in Mandinka, and 13.3% in Wollof.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunohistochemical localization of an inducible form of nitric oxide synthase in various organs of rats treated with Propionibacterium acnes and lipopolysaccharide

Abstract: Immunohistochemical localization of an endotoxin-inducible form of nitric oxide synthase was examined using rabbit polyclonal antibody against the enzyme purified from rat liver. In rats treated with Propionibacterium acnes and lipopolysaccharide, immunostaining was observed in macrophages, occasional lymphocytes, neutrophils and eosinophils in red pulp of spleen, Kupffer cells, endothelial cells and hepatocytes in liver, alveolar macrophages in lung, macrophages and endothelial cells in adrenal glands, and histiocytes, eosinophils, mast cells and endothelial cells in colon. Immunoreactivity was also evident in the following tissues: histiocytes and endothelial cells in kidney; histiocytes and neutrophils in esophagus; macrophages and eosinophils in duodenum; macrophages, some lymphocytes and mast cells in ileum; histiocytes in thymus; and endothelial cells in heart and aorta. Immunoreactivity was not detected in these organs from untreated rats. Positively staining cells in these rat organs appeared within 2.5 h after lipopolysaccharide administration; their number dramatically increased within the next 2.5 h, remained at high levels for a further 19 h, and then decreased over the following 24 h. The number of positive cells appearing correlated well with the nitric oxide synthase activity biochemically determined in the same organs.