Alcohol and tobacco, and the risk of cancers of the upper aerodigestive tract in Latin America: a case-control study.

BACKGROUND: Cancers of the upper aerodigestive tract (UADT; including oral cavity, pharynx, larynx and oesophagus) have high incidence rates all over the world, and they are especially frequent in some parts of Latin America. However, the data on the role of the major risk factors in these areas are still limited. METHODS: We have evaluated the role of alcohol and tobacco consumption, based on 2,252 upper aerodigestive squamous-cell carcinoma cases and 1,707 controls from seven centres in Brazil, Argentina, and Cuba. RESULTS: We show that alcohol drinkers have a risk of UADT cancers that is up to five times higher than that of never-drinkers. A very strong effect of aperitifs and spirits as compared to other alcohol types was observed, with the ORs reaching 12.76 (CI 5.37-30.32) for oesophagus. Tobacco smokers were up to six times more likely to develop aerodigestive cancers than never-smokers, with the ORs reaching 11.14 (7.72-16.08) among current smokers for hypopharynx and larynx cancer. There was a trend for a decrease in risk after quitting alcohol drinking or tobacco smoking for all sites. The interactive effect of alcohol and tobacco was more than multiplicative. In this study, 65% of all UADT cases were attributable to a combined effect of alcohol and tobacco use. CONCLUSIONS: In this largest study on UADT cancer in Latin America, we have shown for the first time that a prevailing majority of UADT cancer cases is due to a combined effect of alcohol and tobacco use and could be prevented by quitting the use of either of these two agents.

TP53 and EGFR mutations in combination with lifestyle risk factors in tumours of the upper aerodigestive tract from South America.

Cancers of the upper aerodigestive tract [(UADT): oral cavity, pharynx, larynx and oesophagus] have high incidence rates in some parts of South America. Alterations in the TP53 gene are common in these cancers. In our study, we have estimated the prevalence and patterns of TP53 mutations (exons 4-10) in 236 UADT tumours from South America in relation to lifestyle risk factors, such as tobacco smoking and alcohol drinking. Moreover, we have conducted a pilot study of EGFR mutations (exons 18-21) in 45 tumours from the same population. TP53 mutation prevalence was high: 59% of tumours were found to carry mutant TP53. We found an association between TP53 mutations and tobacco smoking and alcohol drinking. The mutation rate increased from 38% in never-smokers to 66% in current smokers (P-value for trend = 0.09). G:C>T:A transversions were found only in smokers (15%). Alcohol drinkers carried more G:C>A:T transitions (P = 0.08). Non-exposed individuals were more probable to carry G:C>A:T transitions at CpG sites (P = 0.01 for never-smokers and P < 0.001 for never-drinkers). EGFR mutations were found in 4% of cases. Inactivation of TP53 by mutations is a crucial molecular event in the UADT carcinogenesis and it is closely related to exposure to lifestyle risk factors. EGFR mutations do not appear to be a common event in UADT carcinogenesis in this population.

Prevalence of BRCA1 and BRCA2 gene mutations in families with medium and high risk of breast and ovarian cancer in Brazil

Of all malignant neoplasias affecting women, breast cancer has the highest incidence rate in Brazil. The objective of the present study was to determine the frequency of genetic modifications in families with medium and high risk for breast and ovarian cancer from different regions of Brazil. An exploratory, descriptive study was carried out on the prevalence of the BRCA1 and BRCA2 mutations in case series of high-risk families for breast and/or ovarian cancer. After heredogram construction, a blood sample was taken and DNA extraction was performed in all index cases. The protein truncation test was used to screen for truncated mutations in exon 11 of the BRCA1 gene and in exons 10 and 11 of the BRCA2 gene. Of the 612 individuals submitted to genetic testing, 21 (3.4 percent), 19 women and 2 men, had mutations in the BRCA1 or BRCA2 genes. Of the 19 BRCA1 mutations found in the 18 participants, 7 consisted of ins6kb mutations, 4 were 5382insC, 3 were 2156delGinsCC, 2 were 185delAG, 1 was C1201G, 1 was C3522T, and 1 was 3450del4. With respect to the BRCA2 gene, 3 mutations were found: 5878del10, 5036delA and 4232insA (one case each). The prevalence of germline mutations in the BRCA1 and BRCA2 genes found in the present study was lower than reported by other studies on high-risk Brazilian populations. The inclusion of individuals with medium risk may have contributed to the lower prevalence observed.

Prevalence of BRCA1 and BRCA2 gene mutations in families with medium and high risk of breast and ovarian cancer in Brazil.

Of all malignant neoplasias affecting women, breast cancer has the highest incidence rate in Brazil. The objective of the present study was to determine the frequency of genetic modifications in families with medium and high risk for breast and ovarian cancer from different regions of Brazil. An exploratory, descriptive study was carried out on the prevalence of the BRCA1 and BRCA2 mutations in case series of high-risk families for breast and/or ovarian cancer. After heredogram construction, a blood sample was taken and DNA extraction was performed in all index cases. The protein truncation test was used to screen for truncated mutations in exon 11 of the BRCA1 gene and in exons 10 and 11 of the BRCA2 gene. Of the 612 individuals submitted to genetic testing, 21 (3.4%), 19 women and 2 men, had mutations in the BRCA1 or BRCA2 genes. Of the 19 BRCA1 mutations found in the 18 participants, 7 consisted of ins6kb mutations, 4 were 5382insC, 3 were 2156delGinsCC, 2 were 185delAG, 1 was C1201G, 1 was C3522T, and 1 was 3450del4. With respect to the BRCA2 gene, 3 mutations were found: 5878del10, 5036delA and 4232insA (one case each). The prevalence of germline mutations in the BRCA1 and BRCA2 genes found in the present study was lower than reported by other studies on high-risk Brazilian populations. The inclusion of individuals with medium risk may have contributed to the lower prevalence observed.

High birth weight as an important risk factor for infant leukemia.

In this paper, we compared the birth weight distribution among 201 infant leukaemia (IL) cases with that of 440 noncancer controls enrolled in Brazil in 1999-2005. Compared with the general population and the stratum 2500-2999 g as reference, IL cases weighing 3000-3999 g presented an odds ratio (OR) of 1.68 (95% CI: 1.03-2.76), and those of 4000 g or more, an OR of 2.28 (95% CI: 1.08-4.75), P trend<0.01. Using hospital-based controls, the OR for 4000 g or more, compared to 2500-2999 g, was 1.30 (95% CI: 1.02-1.43) after adjusting for confounders (gender, income, maternal age, pesticide and hormonal exposure during pregnancy). The results suggest that high birth weight is associated with increased risk of IL.

Feasibility study for a long-term follow-up in a historical cohort of Brazilian coal miners.

The first Brazilian historical mortality cohort study on miners was conducted. The cohort consisted of 3224 workers in the underground coal mining industry in southern Brazil. This industry has been operating since 1942 without compliance with any regulatory standards, since there were no relevant national regulations. Over almost 60 years, about 5000 workers were exposed to high levels of radiation. However, later radiation exposure was significantly reduced, particularly that due to radon exposure. Recent radon concentration measurements indicated an average annual exposure to radon progeny of 2.1 WLM, ranging from 0.2 to 7.2 WLM. As radon exposure in the past was unknown, it can be suggested that mine workers have not been working safely as regards the health hazard related to radon and radon progeny exposure. The cohort inclusion criteria are as follows: (a) all male employees who had worked for at least one year at the coal mine; (b) workers with complete workplace information (underground and surface); (c) employment hiring between 1945 and 1997 and (d) the worker must have been alive on 1 January 1979. Through multiple strategies of search it was possible to follow up the members of the cohort with a success rate of 92%. This paper presents the characteristics of the study population and provides information about the feasibility of conducting a retrospective mortality study in Brazil, taking into account the methodological and logistical difficulties of conducting such a study in a developing country.

Acute leukemia in early childhood.

Acute leukemia in early childhood is biologically and clinically distinct. The particular characteristics of this malignancy diagnosed during the first months of life have provided remarkable insights into the etiology of the disease. The pro-B, CD10 negative immunophenotype is typically found in infant acute leukemia, and the most common genetic alterations are the rearrangements of the MLL gene. In addition, the TEL/AML1 fusion gene is most frequently found in children older than 24 months. A molecular study on a Brazilian cohort (age range 0-23 months) has detected TEL/AML1+ve (N = 9), E2A/PBX1+ve (N = 4), PML/RARA+ve (N = 4), and AML1/ETO+ve (N = 2) cases. Undoubtedly, the great majority of genetic events occurring in these patients arise prenatally. The environmental exposure to damaging agents that give rise to genetic changes prenatally may be accurately determined in infants since the window of exposure is limited and known. Several studies have shown maternal exposures that may give rise to leukemogenic changes. The Brazilian Collaborative Study Group of Infant Acute Leukemia has found that mothers exposed to dipyrone, pesticides and hormones had an increased chance to give birth to babies with infant acute leukemia [OR = 1.48 (95%CI = 1.05-2.07), OR = 2.27 (95%CI = 1.56-3.31) and OR = 9.08 (95%CI = 2.95-27.96)], respectively. This review aims to summarize recent clues that have facilitated the elucidation of the biology of early childhood leukemias, with emphasis on infant acute leukemia in the Brazilian population.

Acute leukemia in early childhood

Acute leukemia in early childhood is biologically and clinically distinct. The particular characteristics of this malignancy diagnosed during the first months of life have provided remarkable insights into the etiology of the disease. The pro-B, CD10 negative immunophenotype is typically found in infant acute leukemia, and the most common genetic alterations are the rearrangements of the MLL gene. In addition, the TEL/AML1 fusion gene is most frequently found in children older than 24 months. A molecular study on a Brazilian cohort (age range 0-23 months) has detected TEL/AML1+ve (N = 9), E2A/PBX1+ve (N = 4), PML/RARA+ve (N = 4), and AML1/ETO+ve (N = 2) cases. Undoubtedly, the great majority of genetic events occurring in these patients arise prenatally. The environmental exposure to damaging agents that give rise to genetic changes prenatally may be accurately determined in infants since the window of exposure is limited and known. Several studies have shown maternal exposures that may give rise to leukemogenic changes. The Brazilian Collaborative Study Group of Infant Acute Leukemia has found that mothers exposed to dipyrone, pesticides and hormones had an increased chance to give birth to babies with infant acute leukemia [OR = 1.48 (95 percentCI = 1.05-2.07), OR = 2.27 (95 percentCI = 1.56-3.31) and OR = 9.08 (95 percentCI = 2.95-27.96)], respectively. This review aims to summarize recent clues that have facilitated the elucidation of the biology of early childhood leukemias, with emphasis on infant acute leukemia in the Brazilian population.

High radon exposure in a Brazilian underground coal mine.

The main source of radiation exposure in most underground mining operations is radon and radon decay products. The situation of radon exposure in underground mining in Brazil is still unknown, since there has been no national regulation regarding this exposure. A preliminary radiological survey in nonuranium mines in Brazil indicated that an underground coal mine in the south of Brazil had high radon concentration and needed to be better evaluated. This paper intends to present an assessment of radon and radon decay product exposure in the underground environment of this coal mining industry and to estimate the annual exposure to the workers. As a product of this assessment, it was found that average radon concentrations at all sampling campaign and excavation sites were above the action level range for workplaces of 500-1500 Bq m(-3) recommended by the International Commission on Radiological Protection--ICRP 65. The average effective dose estimated for the workers was almost 30 times higher than the world average dose for coal miners.

Breast cancer mortality among Ashkenazi Jewish women in São Paulo and Porto Alegre, Brazil.

BACKGROUND: Increased BRCA1 and BRCA2 germline mutation rates have been reported in Ashkenazi Jewish women in North America, Europe and Israel, and have been mentioned as possibly related to a higher incidence of breast and ovarian cancer among these communities. The present study was carried out with the aim of obtaining evidence on the magnitude of breast cancer as a cause of death among Ashkenazi women in Brazil. METHODS: We reviewed all death certificates archived in the Jewish Burial Societies of São Paulo (1971-1997) and Porto Alegre (1948-1997), two of the main and oldest Jewish communities in Brazil. Breast cancer observed deaths were compared with expected deaths according to breast cancer mortality in the general population. RESULTS: The observed ratios were approximately quite close to unity, suggesting a similar breast cancer mortality pattern among the Ashkenazi population and the general population in both cities. These results maintain similar behavior regardless of whether analyzed before or after the mid-1980s, when mammography came to be increasingly performed in Brazil. Cancer proportional mortality ratios were 1.04 (0.83-1.29) in São Paulo and 1.16 (0.84-1.57) in Porto Alegre before 1985, and 1.17 (1.00-1.44) and 1.21 (0.81-1.79), respectively, between 1985 and 1997. Some evidence of the maintenance of protective risk factors such as high parity has been observed among Ashkenazi women in São Paulo. CONCLUSION: A quite similar breast cancer mortality pattern was observed between Ashkenazi Jewish women and the general population in São Paulo and Porto Alegre, Brazil. These results may suggest an environmental role on germ mutation expression reported in this ethnic group.

[Evaluation of the nutritional status of the Parkatêjê indigenous community in Bom Jesus do Tocantins, Pará, Brazil]. / Avaliação do estado nutricional da comunidade indígena Parkatêjê, Bom Jesus do Tocantins, Pará, Brasil.

The nutritional status of the Mãe-Maria indigenous community in Bom Jesus do Tocantins, Pará State, Brazil, was ascertained in a descriptive study in which ninety percent of the total population (278 individuals) agreed to participate. Weight-for-height and height-for-age indices and Body Mass Index (BMI) were ascertained for children and adults by gender, respectively, as were weight and height means in adolescents. Compared to NCHS curves, overweight and chronic malnutrition were observed, respectively, in 6.7 and 8.6 % of all children under 10 years old (104). Weight means were similar among Indians and NCHS adolescents, while height means were lower among the former. Overweight prevalence (BMI 25 to 29) was 23.7% among male adults and 50.0% among female adults, and obesity (BMI > 30) was observed in 12.5% of adult females.

[Electric power generation and transmission: the impact on indigenous peoples in Brazil]. / Geração e transmissão da energia elétrica: impacto sobre os povos indígenas no Brasil.

This paper presents an overview of the effects of electric power generation and transmission on indigenous communities in Brazil. According to data from FUNAI (the Brazilian government's Board of Indian Affairs), there are 156 cases of direct impact, present or future, of the electric power sector on Indian settlements geographically distributed throughout Brazil, 65% of which are located in the Northern Region of the country. The principal complaints by indigenous communities relate to the direct effects of flooding following construction of hydroelectric dams, destruction of sacred sites like cemeteries, mosquito proliferation, and health-related hazards such as malaria and other infectious diseases, decrease in game for hunting, crowding out of farm land, and increased invasion of indigenous lands. Future perspectives include a scenario with further construction of hydroelectric dams, especially in the Amazon region, with possible similar effects on indigenous communities.

[Association between dietary factors and brain tumors in adults: a review]. / Associação entre fatores da dieta e tumores de cérebro em adultos: uma revisão da literatura.

This paper reviews the scientific literature published from 1986 to 1999 assessing the relationship between dietary factors and brain tumors in adults. The work aimed to describe the estimated associations and to discuss methodological aspects that might influence the results. The studies generally appear to show a moderate association between dietary factors and brain tumors. There is evidence that N-nitroso compounds enhance the risk of developing such tumors and that consumption of fruits and vegetables can inhibit them. Use of proxies in most of the studies may have introduced bias, thereby contributing to some inconsistent observations. Epidemiological research on diet and brain tumors should consider other components of food besides N-nitroso compounds. It is important to carefully assess exposure periods and to prevent bias related to control selection and recall.

[Risk factors for breast cancer among rural Teréna Indian women in the State of Mato Grosso do Sul, Brazil]. / Fatores de risco para câncer de mama em mulheres indígenas Teréna de área rural, Estado do Mato Grosso do Sul, Brasil.

In order to evaluate the distribution of selected risk factors for breast cancer among Teréna Indian women in the State of Mato Grosso do Sul, Brazil, two samples were interviewed, respectively, in 1995 (330 women from ten Indian villages) and 1997 (40 women from the Limão Verde village). Reproductive history, diet characteristics, and family and personal medical history were investigated and body mass index was measured. In the larger sample, mean age at menarche was 12.3 years (30% at 13 years old or later), 86% of women reported one or more pregnancies (42% reporting 5 or more), 71% reported three or more pregnancies, mean age at first pregnancy was 18.9 years (3.8% after 28 years), mean duration of breastfeeding was 84 months, and 70% reported menopause before age 50. Dietary pattern in the smaller sample revealed a high intake of fruits, vegetables, pasta, and tubers and scarce intake of red meat and chicken; 50 of the women (95% CI: 34.1-65.9) presented overweight (BMI 25-29) and 27% (95% CI: 15.1-44.1) obesity (BMI > 29).

[Using food frequency questionnaire in past dietary intake assessment]. / Uso do questionário de freqüência na avaliação do consumo alimentar pregresso.

This paper aims to discuss which one is the best estimator of past diet: a retrospective report or a recent diet recall. The analysis included 13 articles published between 1984-1997 and selected from a MEDLINE search and from other reviews on this subject. The selection criterion was the use of a food frequency questionnaire (FFQ) in a validation study of retrospective report of dietary intake in remote past. Literature review shows that even taking into account misclassification, retrospective report of diet usually yields to a more reliable estimate of past diet pattern than current report. Past diet recall was strongly influenced by current intake and by diet patterns change. Analyzed investigations indicate that agreement between original and retrospective report was higher either for foods eaten rarely or frequently and lower for foods moderately consumed. This review allows considering the FFQ as a valuable instrument when studying the role of diet on the etiology of chronic diseases.

Survival analysis in a sample of oral cancer patients at a reference hospital in Rio de Janeiro, Brazil.

This article gives the results of a 5-year survival analysis of 371 oral cancer patients who received medical care at a cancer reference hospital in Rio de Janeiro between 1986 and 1987. Patient profiles based on selected risk factors for oral cancer and 5-year survival based on prognostically relevant variables are described.

Smoking in Latin America: a major public health problem.

Smoking has become a major public health problem in Latin America, and its scope varies from country to country. Despite difficulty in obtaining methodologically consistent data for the region, we analyzed the results from prevalence surveys in 14 Latin American countries. We observed that smoking prevalence among men varied from 24.1% (Paraguay) to 66.3% (Dominican Republic) and among women from 5.5% (Paraguay) to 26,6% (Uruguay). By applying point prevalence data to the stage model of the tobacco epidemic in developed countries, we concluded that the Latin American countries are in stage 2, i.e., with a clearly rising prevalence among men, a prevalence for women that is beginning to increase, and mortality attributable to smoking among men still not reflecting peak prevalence. None of the countries analyzed appeared to have reached stage 3, in which one observes a downward trend in prevalence of smoking among men and peak prevalence among women, with broad impact on tobacco-related mortality. The only exception appears to be Paraguay, which is still emerging from stage 1, i.e., with low prevalence rates among men, too. Nevertheless, high lung cancer mortality rates in Uruguay and Argentina are comparable to those of the developed countries.

Cancer cluster among young Indian adults living near power transmission lines in Bom Jesus do Tocantins, Pará, brazil.

A case study was carried out to explore the occurrence of a cancer cluster in 1992 among young indian adults adults living in an Amazonian village near two 500 kV power transmission lines that began operating a decade ago. Current blood levels of DDT and organophosphorus pesticides and metal levels in hair samples were measured. Extremely low magnetic field exposure was determined during current daily activities carried out by the Indian villagers. Taking into account the cancer incidence rates in different Brazilian cities, the probability of the occurrence of this cluster by chance was considered remote (p< 0.003, Poisson distribution). High blood levels of p,p'-DDT (median levels ranging from 26 to 58 ppb) were observed. As a whole, this community showed a pattern of low exposure to organophosphorus pesticides, and high recent exposure was only observed in a few blood samples. Continuous exposure to extremely low electromagnetic fields originated in the power transmission lines (which reached 95.0 mG under the lines) was observed on several opportunities during daily activities carried out by Indian villagers. Further observational studies should evaluate the interaction between exposure to extremely low electromagnetic fields and prior exposure to tumor initiators in cancer development.