Abstract 2176: Obesity and risk of colorectal cancer: A Mendelian randomization study
Notice bibliographique
Résumé
Abstract Background: Obesity has been consistently linked to higher risk of colorectal cancer (CRC) in men, whereas the association is generally lower in women. Although these findings come from well conducted epidemiologic studies, it is difficult to exclude all other explanations for associations in observational studies, such as measurement error and other forms of bias, reverse causality and confounding. Mendelian randomization studies, using instrumental variables (IVs), can overcome some of the inherent limitations of observational studies and provide an unbiased and unconfounded estimate of the causal association between an exposure and outcome. Objective: We used genetic variants that are associated with body mass index (BMI) or waist-hip ratio (WHR) to examine the causal association between obesity and CRC. Methods: We used epidemiologic and genetic data from 10 226 CRC cases and 10 286 controls of European ancestry from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) or the Colon Cancer Family Registry (CCFR). The primary Mendelian randomization analysis was performed using a genetic risk score, derived from 77 established “BMI-increasing” genetic variants, as an instrumental variable for higher BMI. We additionally derived a risk score for WHR using 47 variants for WHR. We compared the IV odds ratio (OR) with the OR obtained using a traditional multivariable logistic regression model adjusted for age, sex, smoking status, family history, aspirin use, and HRT use (women). Results: For men and women combined, in traditional multivariable analysis, each 5 kg/m2 increase in BMI was associated with a 24% (95% confidence interval [CI]: 1.17-1.32) increase in risk of CRC. In the IV analysis, the OR was higher (IV-OR per 5 kg/m2=1.54, 95% CI: 1.15-2.06); however, the two estimates were not statistically significantly different (Pdifference=0.07). For men, there was a statistically significant association between BMI and CRC in traditional multivariable analysis (OR per 5kg/m2=1.33, 95% CI: 1.21-1.46), but no association in the IV analysis (IV-OR per 5 kg/m2=1.13, 95% CI: 0.70-1.83). The estimates however were not significantly different (Pdifference=0.56). In contrast, for women, the IV estimate (IV-OR per 5 kg/m2=1.94, 95% CI: 1.33-2.82) was significantly higher than the estimate from the traditional multivariable analysis (OR per 5 kg/m2=1.18, 95% CI: 1.11-1.25; Pdifference=0.01). In secondary analysis, we found a positive association between WHR and CRC in men (IV-OR per 0.1 unit increase=1.84, 95% CI: 1.02-3.31) but no statistically significant association in women (IV-OR per 0.1 unit increase=1.22, 95% CI: 0.75-1.98). Conclusions: Obesity is independently associated with risk of CRC and may confer greater risk of CRC in women than previously reported. The mechanisms remain largely unknown; however these results suggest that visceral abdominal fat may be particularly important for promoting CRC in men. Citation Format: Aaron P. Thrift, Sonja I. Berndt, Andrew T. Chan, Jenny Chang-Claude, Martha L. Slattery, Michelle Cotterchio, Graham Casey, John D. Potter, Polly A. Newcomb, Emily White, Hermann Brenner, Ulrike Peters, Peter T. Campbell. Obesity and risk of colorectal cancer: A Mendelian randomization study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2176. doi:10.1158/1538-7445.AM2014-2176
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,008 | 0,025 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».