Obesity, Metabolic Factors and Risk of Different Histological Types of Lung Cancer: A Mendelian Randomization Study

Background: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. Methods and findings: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01–1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15–2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79–1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84–0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25–2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. Conclusions: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior

Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study.

BACKGROUND: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. METHODS AND FINDINGS: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. CONCLUSIONS: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Essai d'interprétation du sens du substantif Hosiê dans l'Odyssée et dans les Hymnes Homériques

In the Odyssey and in the Homeric Hymns, the substantive ἡ ὁσίη expresses the existence of a divine law who, according to the τιμή and the γέρας, determines the rights and the rituals, essential elements for every god and the duties to which the men must be subject in order to conform to the allocated limits. So the ὁσίη structures the organization of the divine and human worlds.Dans l'Odyssée et dans les Hymnes homériques, le substantif ἡ ὁσίη qualifie l'existence d'une loi divine fixant, en fonction de la τιμή et du γέρας, les droits et les rituels indispensables à chaque dieu pour être reconnu comme tel ainsi que les devoirs auxquels les hommes doivent se soumettre pour se conformer aux limites à eux assignées. L'ὁσίη structure ainsi l'organisation des univers divin et humain.Jay-Robert Ghislaine. Essai d'interprétation du sens du substantif Hosiê dans l'Odyssée et dans les Hymnes Homériques. In: Revue des Études Anciennes. Tome 101, 1999, n°1-2. pp. 5-20

Le vocabulaire du commandement chez Aristophane

The vocabulary of order in Aristophanes is not well represented, but offers some interesting particularities. We establish that the comic poet differentiates political power from the others and does not believe in a strong and just power. Power, in the Athenian democracy, is disparaged and identified with the relation between master and slave. So Aristophanes prefers other relations that are not based only upon domination.Chez Aristophane, le vocabulaire du commandement est peu fourni, mais présente des spécificités intéressantes. Son emploi montre que le poète comique distingue soigneusement le pouvoir politique des autres types de pouvoir. Il montre également qu’il n’existe pas pour le poète de pouvoir fort et juste. Discréditées, les relations de pouvoir dans la démocratie athénienne sont identifiées aux rapports maître-esclave. Elles ont donc tendance à être écartées au profit de relations qui ne se fondent pas uniquement sur des rapports de domination.Jay-Robert Ghislaine. Le vocabulaire du commandement chez Aristophane. In: Ktèma : civilisations de l'Orient, de la Grèce et de Rome antiques, N°36, 2011. pp. 169-183

Avant-propos

Joël Thomas, vu par Philippe Heuzé Si quis erit raros inter numerandus amicos, Quales prisca fides famaque nouit anus, Si quis Cecropiae madidus Latiaeque Mineruae Artibus et uera simplicitate bonus, Si quis erit recti custos, mirator honesti Et nihil arcano qui roget ore deos, Si quis erit magnae subnixus robore mentis : Dispeream, si non hic J. Thomasus erit. La première fois que j’ai parlé avec Joël Thomas, c’était au téléphone, un jour d’é..

Aristophane et Longin ou le sublime en question

International audienc

Au spectacle avec Aristophane : regards échangés et métathéâtre

At the Spectacle with Aristophanes : Exchanged Looks and Metatheatre ̶ Through a precise study of the verbs ὁράω, βλέπω, θεάομαι, σκοπέω and σκέπτομαι, the author analyses how Aristophanes stages the gaze in his comedies. The action of seeing assumes a dynamic exchange between the subject and object in vision. This movement allows the character to build his identity. It also allows the development of a kind of community between characters and spectators. This conception of vision has a fundamental impact on the status of the spectator, the definition of the theatrical space and the distinction between fact and fiction.Grâce à une étude précise des verbes ὁράω, βλέπω, θεάομαι, σκοπέω et σκέπτομαι, l’auteur analyse la façon dont Aristophane met en scène le regard dans ses comédies. L’action de voir suppose un échange dynamique entre le sujet et l’objet de la vision. Ce mouvement permet au personnage de construire son identité et il permet aussi d’élaborer une sorte de communauté entre les acteurs et les spectateurs. Cette conception de la vision a des conséquences fondamentales sur le statut du spectateur, la définition de l’espace théâtral et la distinction entre la réalité et la fiction.Jay-Robert Ghislaine. Au spectacle avec Aristophane : regards échangés et métathéâtre. In: L'antiquité classique, Tome 85, 2016. pp. 19-35

L’œil et sa mise en scène chez Aristophane

International audienceCet ouvrage réunit dix contributions de chercheurs sur les réponses qu’on donne aujourd’hui à la question des origines rituelles de la comédie ancienne et de son articulation avec l’histoire des idées politiques. Il fait ainsi l’inventaire, trente ans après la parution de l’ouvrage Le Carnaval et la politique de Jean-Claude Carrière, des acquis que la recherche actuelle en retient. À partir du cas exemplaire de la comédie ancienne, il produit une nouvelle somme sur une question beaucoup plus vaste, celle de l’opposition entre l’interprétation ritualiste et l’interprétation politique des sociétés anciennes