Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3,800 aerodigestive cancer cases and 5,200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P ¼ 10 À10 and 10 À9 , respectively). These effects became more apparent with increasing alcohol consumption (P for trend ¼ 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology.The alcohol dehydrogenase (ADH) pathway includes seven distinct ADH genes, a key candidate gene group for aerodigestive cancers 1-3 .Studies of aerodigestive cancer in populations of European origin have focused on ADH1C with little evidence of any effect 4 . We previously reported an association for ADH1B R48H (rs1229984) in a central European (CE) population 5 and now consider the effect of this and five other ADH variants in an expanded study comprising 809 aerodigestive cancer cases and 2,586 controls from the CE study as well as a further 3,067 aerodigestive cancer cases and 2,692 controls from two other studies in Europe (ARCAGE study) and Latin America (LA study) (total of 3,876 cases and 5,278 controls). All three studies were coordinated by the International Agency for Research on Cancer (IARC) and followed a similar protocol (Supplementary Methods online). Of the 3,876 cases, 1,790 were cancers of the oral cavity or pharynx, 1,659 were cancers of the hypopharynx or larynx and 427 were cancers of the esophagus (Supplementary Table 1 online). Cases with a histology other than squamous cell were excluded.The HapMap Consortium has genotyped 163 SNPs in the vicinity of the ADH gene cluster with a minor allele frequency (MAF) of 4% or more in the CEPH Utah (CEU) population 6 . Inspection of the linkage disequilibrium (LD) pattern across this region indicates that ADH1A, ADH1B, ADH1C, ADH4, ADH5 and ADH6 are relatively highly correlated, whereas ADH7 showed little correlation with the remaining six ( Supplementary Fig. 1a online). From all verified missense SNPs in the seven ADH genes found in both the NCBI SNP and SNP500 databases 7 , we selected eight that had a MAF 4 4% in the CEU population. Three missense SNPs in ADH4 (rs1126671, rs1126673 and rs1042364) were in strong LD, and thus were genotyped by the highly correlated tagging SNP rs1984362 (r 2 4 0.89). In total, we genotyped six genetic variants (five missense SNPs and one tagging SNP) in all three studies (Table 1 and Supplementary Table 2 online).In the pooled analysis on all 3,876 cases and 5,278 controls, four variants reported a significant association (Supplementary Table 3 online). The most prominent was with rs1229984 (in ADH1B; OR for codominant model ¼ 0.59 (95% CI ¼ 0.50-0.69); P under codominant model ¼ 8 Â 10 À10 ). This variant w...

The proposed nomograms can help physicians and patients predict the 5 year probability of LE after ALND for breast cancer. Free online versions of the nomograms are available at http://www.lymphedemarisk.com/ .

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Oropharyngeal squamous cell carcinoma is less aggressive in the HPV16 E6/E7 positive serology patients. HPV16 E6/E7 antibody is a clinically sensible surrogate prognostic marker of oropharyngeal squamous cell carcinoma.

The contribution of BRCA1 and BRCA2 to breast cancer incidence in Brazil has not yet been explored. In order to estimate the proportion of breast cancers due to BRCA1 and BRCA2 mutations in Brazil, we conducted a study of unselected breast cancer patients from Rio de Janeiro, Brazil. We enrolled 402 women with breast cancer from a large public hospital and two private medical clinics in the city. A detailed family history was obtained from each patient and a blood sample was obtained for DNA analysis. Mutations in BRCA1 and BRCA2 were sought using a combination of techniques, but all mutations were confirmed by direct sequencing. Overall, nine mutations were identified (six in BRCA1 and three in BRCA2) representing 2.3% of the total. The most common mutation, 5382insC in BRCA1, was seen five times and accounted for 56% of all identified mutations. A second mutation, in BRCA2 (6633del5) was seen in two unrelated women. In summary, BRCA1 and BRCA2 mutations are not uncommon in Brazilian women with breast cancer. It appears that a small number of founder mutations may be predominant. Moreover, a small number of founder mutations may be prevalent in Brazil, raising the possibility that a rapid and inexpensive genetic test may be developed to screen for inherited susceptibility to breast cancer in Brazil.

Many human cancers develop as a result of exposure to risk factors related to the environment and ways of life. The aim of this study was to estimate attributable fractions of 25 types of cancers resulting from exposure to modifiable risk factors in Brazil. The prevalence of exposure to selected risk factors among adults was obtained from population-based surveys conducted from 2000 to 2008. Risk estimates were based on data drawn from meta-analyses or large, high quality studies. Population-attributable fractions (PAF) for a combination of risk factors, as well as the number of preventable deaths and cancer cases, were calculated for 2020. The known preventable risk factors studied will account for 34% of cancer cases among men and 35% among women in 2020, and for 46% and 39% deaths, respectively. The highest attributable fractions were estimated for tobacco smoking, infections, low consumption of fruits and vegetables, excess weight, reproductive factors, and physical inactivity. This is the first study to systematically estimate the fraction of cancer attributable to potentially modifiable risk factors in Brazil. Strategies for primary prevention of tobacco smoking and control of infection and the promotion of a healthy diet and physical activity should be the main priorities in policies for cancer prevention in the country.

A distribuição desigual das doenças crônico-degenerativas tem sido atribuída aos diferentes graus de transformação social em diversas populações. Estudos internacionais em populações indígenas submetidas a mudanças em seus estilos de vida têm mostrado prevalências elevadas de hipertensão arterial e de outros fatores de risco cardiovasculares. Foi feito um estudo de prevalência desses fatores de risco na população adulta das aldeias indígenas Sapukai, Paraty-Mirim e Araponga no Rio de Janeiro. Após recenseamento, a população teve os dados coletados através de entrevista e de avaliações clínicas e bioquímicas. O universo estudado foi de 80 homens e 71 mulheres. As prevalências em toda a amostra foram respectivamente para: hipertensão arterial (4,8%, 2,6% e 7,4%); sobrepeso (26,7%, 19,5% e 34,8%) e obesidade (4,8%, 3,9% e 5,8%); alterações lipídicas do colesterol total (2,8%, 2,7% e 2,9%) e dos triglicerídios (12,6%, 9,5% e 15,9%). Todas as prevalências foram superiores no sexo feminino e maiores nas idades mais avançadas. Os resultados sugerem que a população avaliada encontra-se sob risco intermediário para as doenças crônicas, mostrando que devem ser empreendidos esforços para controlar os fatores de risco.

As suicide rates have increased in rural areas in Brazil, it was postulated that pesticide exposure may play a role in this phenomenon. Our study compared the suicide mortality rates observed among agricultural workers from a pesticide-intensive area in Brazil to the suicide mortality frequency noted in three reference populations. In addition, hospitalization rates attributed to suicide attempts and mood disorders including depression in residents of the same agricultural area were compared to two reference populations. Finally, data on pesticide sales per agricultural worker were obtained for each city of Rio de Janeiro State and suicide mortality risk was then calculated according to the quartiles of pesticide sales per agricultural workers, using the first quartile as reference. Agricultural workers were at greater risk for lethality due to suicide when compared to all three reference populations. In addition, residents of the same study area showed higher hospitalization rates by suicide attempts and mood disorders than observed in comparison populations. Results also showed that the risk of death by suicide was significantly higher among agricultural workers who lived in areas of Rio de Janeiro State displaying higher rates of pesticide expenditure per agricultural worker. These results suggest that pesticide exposure may indeed increase the risk of suicide frequency, especially among agricultural workers.