Familial cancer aggregation and the risk of lung cancer

CONTEXT: Around 90% of lung cancer worldwide is attributable to cigarette smoking, although less than 20% of cigarette smokers develop lung cancer. Other factors such as diet, chronic lung diseases, occupation and possibly environmental agents also contribute to this cancer. Genetic factors seem to play a role in lung cancer, but the precise characteristics influencing lung cancer susceptibility are not known, since genetic factors are easily obscured by the strong environmental determinants of lung cancer, particularly smoking. OBJECTIVE: To estimate the effect that cancer occurrence among first-degree relatives has on the risk of lung cancer. DESIGN: Hospital-based case-control study. SETTING: The metropolitan region of São Paulo, Brazil. PARTICIPANTS: 334 incident lung cancer cases and 578 controls matched by hospitals. MAIN MEASUREMENTS: By means of a structured questionnaire, cases and controls were interviewed about cancer occurrence in first-degree relatives, tobacco smoking, exposure to passive smoking, occupation, migration and socioeconomic status. Non-conditional logistic regression was used to calculate the risk of familial cancer aggregation, the effect of cancer in first-degree relatives and smoking in conjunction, and for controlling confounders. RESULTS: The adjusted odds ratio (OR) revealed a slight, but not statistically significant, excess risk of lung cancer for subjects with a history of lung cancer in relatives (OR 1.21; 95% confidence interval [CI] 0.50 -- 2.92). The same was found among those with a history of other tobacco-related cancers in relatives (OR 1.36; 95% CI 0.87 -- 2.14). A step gradient effect was observed regarding lung cancer risk, in accordance with increases in the number of pack-years of cigarette consumption. An interaction between familial cancer aggregation and tobacco smoking was detected. CONCLUSIONS: A mildly elevated risk of lung cancer among persons with a positive history of lung and other tobacco-related cancers was observed. The finding of an interaction between the variables of familial cancer aggregation and smoking suggests that familial cancer aggregation could be considered as a marker of susceptibility, increasing the risk of lung cancer among smokers. These results improve our knowledge of lung carcinogenesis and can guide future cancer genetic studies.INTRODUÇÃO: Cerca de 90% dos casos de câncer de pulmão no mundo são atribuíveis ao tabagismo, porém menos de 20% dos fumantes desenvolvem câncer de pulmão. Fatores como dieta, doenças pulmonares crônicas, ocupação e, possivelmente, exposições ambientais também têm papel na etiologia desse câncer. Os fatores genéticos parecem influir na ocorrência da doença, mas as características que influenciam a suscetibilidade à neoplasia pulmonar não são precisamente conhecidas, obscurecidas pela forte influência dos fatores ambientais na determinação da doença, particularmente o tabagismo. OBJETIVOS: Estimar o efeito da ocorrência de câncer em parentes de primeiro grau no risco de câncer de pulmão. TIPO DE ESTUDO: Estudo caso-controle de base hospitalar. LOCAL: Região Metropolitana de São Paulo. PARTICIPANTES: 334 casos de neoplasia pulmonar e 578 controles emparelhados por hospital. VARIÁVEIS ESTUDADAS: Casos e controles foram entrevistados com respeito ao passado de neoplasias em parentes de primeiro grau, tabagismo, tabagismo passivo, ocupação, migração e status socioeconômico. Utilizou-se a regressão logística não-condicional para calcular o risco de câncer em familiares, o efeito conjunto de câncer em familiares e uso de tabaco, e para controlar potenciais variáveis de confusão. RESULTADOS: O odds ratio (OR) ajustado revelou um discreto excesso de risco para câncer de pulmão, não estatisticamente significante, entre os indivíduos com história de câncer de pulmão na família (OR 1,21; intervalo de confiança de 95% [IC 95%] 0,50 -- 2,92) ou entre aqueles com história de outros cânceres relacionados ao tabaco na família (OR 1,36; IC 95% 0,87 --2,14). Foi observado um efeito dose-resposta positivo para o risco de câncer de pulmão de acordo com o aumento do consumo de cigarros. Detectou-se uma interação entre as variáveis câncer na família e tabagismo. CONCLUSÕES: Observou-se um discreto aumento do risco de câncer de pulmão entre indivíduos com história positiva na família de câncer de pulmão e outros cânceres relacionados ao tabaco. Esses resultados sugerem que a presença de aglomerados de câncer na família pode ser considerada como um marcador de suscetibilidade e aumenta o risco de câncer de pulmão entre os fumantes. A interação detectada entre as variáveis agregadas de câncer na família e tabagismo no risco de câncer de pulmão é uma contribuição no conhecimento dos mecanismos da carcinogênese e poderá orientar futuras pesquisas no campo da genética do câncer.University of São Paulo Public Health School Department of EpidemiologyWorld Health Organization International Agency for Research on Cancer Unit of Environmental Cancer EpidemiologyFederal University of São Paulo Department of Preventive MedicineUNIFESP, Department of Preventive MedicineSciEL

Nonmalignant respiratory disease mortality among woodworkers participating in the American Cancer Society Cancer Prevention Study-II (CPS-II)

Nonmalignant respiratory disease (NMRD) mortality was examined among woodworkers participating in the American Cancer Society’s CPS-II cohort study. During the 6-year prospective follow-up, there were 97 NMRD deaths among 11,541 men reporting employment in wood-related occupations and 1,338 NMRD deaths among 317,424 men reporting no exposure to wood dust or wood-related jobs. Relative risks, adjusted for age and smoking, were calculated using Poisson regression. A small excess of NMRD was observed among woodworkers. However, the relative risk was higher among woodworkers who did not report exposure to wood dust (RR = 1.52, 95% CI = 1.18–1.97) than those who did (RR = 1.27, 95% CI = 0.91–1.77), and no clear trend with duration of exposure was observed. An excess of NMRD was observed among woodworkers reporting exposure to asbestos (RR = 1.59, 95% CI = 0.85–2.96), as well as the small number of woodworkers reporting exposure to formaldehyde (RR = 1.95, 95% CI = 0.63–6.06), but men not reporting exposure to these substances also had an excess risk. Although limited by a short follow-up period and crude indicators of exposure, the strengths of this analysis were the ability to compare woodworkers to a similar, healthy population and to adjust for the effects of smoking. Cohort studies with better exposure information are needed to examine the role of occupational exposures among woodworkers in the etiology of respiratory disease

Cancer mortality and wood dust exposure among participants in the American Cancer Society Cancer Prevention Study-II (CPS-II).

In 1994, the International Agency for Research on Cancer (IARC) classified wood dust as a human carcinogen, based on very strong evidence of a carcinogenic risk of sino-nasal cancer. Excesses of other cancers, including lung and stomach, have been reported among persons employed in wood industries or occupationally exposed to wood dust, but not as consistently. We investigated such possible associations using the mortality experience of 362,823 men enrolled in the American Cancer Society’s Cancer Prevention Study—II in 1982 and followed up for 6 years. Within this group, 45,399 men (12.5%) reported either employment in a wood-related occupation or exposure to wood dust or both. Among woodworkers, a small but significant excess risk was found for all causes of death (RR 1.17 (95% CI 1.11–1.24)) and for total malignancies (RR 1.17 (1.05–1.30)). Among men who reported exposure to wood dust, there was an elevated risk of total mortality (RR 1.07 (1.03–1.11)), total malignancies (RR 1.08 (1.01—1.15)), and lung cancer (RR 1.17 (1.04–1.31)). Among woodworkers, a significant trend (P = 0.02) of increasing risk of lung cancer with increasing duration of exposure was observed. An unexpected, significantly increased mortality from prostate cancer was observed in both wood-employed and wood-exposed, and a twofold increased risk of fatal brain cancer was seen among the former. Lung cancer mortality was especially high among woodworkers who also reported exposure to asbestos or formaldehyde, and it appears that exposure to these known carcinogens may partly explain the observed increased risks. Excess sino-nasal cancer was not observed, but the number of cases was small

A genetic intervention.

A tool that analyzes the genome of parasites found in the blood of malaria patients can help inform policy decisions on how best to tackle the rise in drug-resistant infections

Power transformer model in railway applications based on bond graph and parameter identification

Validation and verification are the most important issues in railway applications due to cost and security reasons. Therefore, having a model of the system would be necessary in this case. Due to non-ideal test conditions in industrial applications, an accurate parameter identification process has to be defined. In this paper, bond graph method is used to model energy exchanges within components of a traction chain. More precisely, the non-linear transformer model and its parameter identification is studied. In the case of non-ideal test conditions, the usual Jiles-Atherton parameter identification procedure can not be performed. Regarding state of the art, the Jiles-Atherton parameter identification is discussed. It is highlighted that an uncomplete hysteresis cycle, including extremum point and coercive field are mandatory for an accurate parameter identification. The proposed identification process is applied to a real application case. The obtained parameters are then inserted into the overall system model. The consecutive simulations are compared to experimental data obtained through traction chain test bench

Duplications of KIAA1549 and BRAF screening by Droplet Digital PCR from formalin-fixed paraffin-embedded DNA is an accurate alternative for KIAA1549-BRAF fusion detection in pilocytic astrocytomas

Pilocytic astrocytomas represent the most common glioma subtype in young patients and account for 5.4% of all gliomas. They are characterized by alterations in the RAS–MAP kinase pathway, the most frequent being a tandem duplication on chromosome 7q34 involving the BRAF gene, resulting in oncogenic BRAF fusion proteins. BRAF fusion involving the KIAA1549 gene is a hallmark of pilocytic astrocytoma, but it has also been recorded in rare cases of gangliogliomas, 1p/19q co-deleted oligodendroglial tumors, and it is also a common feature of disseminated oligodendroglial-like leptomeningeal neoplasm. In some difficult cases, evidence for KIAA1549-BRAF fusion is of utmost importance for the diagnosis. Moreover, because the KIAA1549-BRAF fusion constitutively activates the MAP kinase pathway, it represents a target for drugs such as MEK inhibitors, and therefore, the detection of this genetic abnormality is highly relevant in the context of clinical trials applying such new approaches. In the present study, we aimed to use the high sensitivity of Droplet Digital PCR (DDPCR™) to predict KIAA1549-BRAF fusion on very small amounts of formalin-fixed paraffin-embedded tissue in routine practice. Therefore, we analyzed a training cohort of 55 pilocytic astrocytomas in which the KIAA1549-BRAF fusion status was known by RNA sequencing used as our gold standard technique. Then, we analyzed a prospective cohort of 40 pilocytic astrocytomas, 27 neuroepithelial tumors remaining difficult to classify (pilocytic astrocytoma versus ganglioglioma or diffuse glioma), 15 dysembryoplastic neuroepithelial tumors, and 18 gangliogliomas. We could demonstrate the usefulness and high accuracy (100% sensitivity and specificity when compared to RNA sequencing) of DDPCR™ to assess the KIAA1549-BRAF fusion from very low amounts of DNA isolated from formalin-fixed paraffin-embedded specimens. BRAF duplication is both necessary and sufficient to predict this fusion in most cases and we propose that this single analysis could be used in routine practice to save time, money, and precious tissue

New, primitive termites (Isoptera) from Early Cretaceous ambers of France and Lebanon

This is the publisher's version, also available electronically from palaeodiversity.org.Three new genera and species of primitive termites (Isoptera) are described and figured from Early Cretaceous French and Lebanese ambers: Santonitermes chloeae ENGEL, NEL & PERRICHOT, n. gen., n. sp., from an imago preserved in Charentese amber (Albian–Cenomanian); Syagriotermes salomeae ENGEL, NEL & PERRICHOT, n. gen., n. sp., from an alate detected in opaque amber from the same locality and reconstructed using synchrotron microtomographic imaging; and Lebanotermes veltzae ENGEL, AZAR & NEL, n. gen., n. sp., from an alate preserved in Lebanese amber (Aptian). The three genera exhibit primitive features of the Meiatermes-grade of early isopteran genera (sensu ENGEL et al. 2009). In addition, three further fragmentary specimens from Lebanon amber are reported, each apparently distinct from Lebanotermes n. gen. and the previously described Melqartitermes ENGEL et al., 2007. The new fossils further document the diversity and morphological disparity of ‘lower’ termite groups during the Early Cretaceous, highlighting the importance of palaeontological material for understanding isopteran phylogeny as well as the diversification of Isoptera in the latest Jurassic and Early Cretaceous

Creative collaboration in citizen science and the evolution of ThinkCamps

This chapter discusses how to harness the potential of creative collaboration through ThinkCamp events – an ‘unconference’ style event with an open and creative environment designed to foster co-creation, co-design and collaborative thinking at key points in the citizen science research cycle. It draws on the authors’ experiences of running (and participating in) creative collaborative events and explores their potential to support inclusive, co-creational approaches to citizen science. Finally, it makes specific recommendations for project initiators, event organisers and policymakers

Identification des paramètres d’un transformateur d’un banc de test ferroviaire à échelle réelle

Cette étude aborde le problème de l’identification in situ des paramètres d’un modèle de transformateur mis en œuvre dans une chaine de traction ferroviaire. Le modèle considéré permet de rendre compte du comportement non linéaire de l’inductance magnétisante du transformateur. L’identification se base sur des données expérimentales où le cycle B(H) n’est pas considéré dans son intégralité. Des résultats expérimentaux et des simulations sont comparés afin de valider la démarche et le modèle