Excess body weight, exogenous hormones, and polymorphisms in steroid metabolism: Links with hereditary colorectal cancer
Notice bibliographique
Résumé
Consistent with the theme of hormonal influence on colorectal cancer, the second objective in this thesis sought to identify the associations between risk of incident colorectal cancer and exogenous hormone-use (hormonal contraceptives and postmenopausal hormone-use). As above, a case-control study design was implemented. Hormonal contraceptives (OR: 0.79) and postmenopausal hormones (OR: 0.67) were inversely linked with colorectal cancer risk. The reduced risks were quite consistent across subgroups of familial risk of cancer and microsatellite instability status. A potential age effect was indicated for age at first use of hormonal contraceptives; women who began using these agents prior to age 22 years experienced a greater reduced risk of colorectal cancer (OR: 0.6) than did women who initiated use at age>30 y (OR: 0.92). The objective of this thesis was to examine the influence of hormonal factors on the risk of colorectal cancer from three perspectives. First, adiposity, height, and weight gain (e.g. indicators of endogenous hormone exposure) were assessed as risk factors for incident colorectal cancer in a population based case-control study from Ontario and Newfoundland. Self-reported family history of cancer and information on lifestyle and demographic factors were collected; data were used from 2,696 cases and 2,668 controls. Colorectal cancer was positively linked with obesity (ORs: 1.75 and 1.82; recent and past BMI, respectively) and weight gain since age 20 years (OR: 1.59) in men; the observed risks were consistent in subgroups of familial risk of cancer and tumour microsate1lite instability status. Among women, no associations were observed between adiposity or weight gain and colorectal cancer risk. The null associations persisted in premenopausal and postmenopausal women, and across strata of familial risk of cancer and microsatellite instability. Height, however, was positively linked with disease risk in women (OR: 2.36). That obesity was associated with increased risk in men, but not in women, may be explained by androgen conversion to estradiol in the adipocyte, as several lines of evidence suggest that estrogen-related hormones are inversely linked with colorectal cancer risk. These data provide support for a hormonal influence on colorectal tumourigenesis. From a clinical and public health perspective, these findings suggest that men who are overweight or obese and who report a familial risk of cancer may represent a key group for interventions aimed at the prevention and control of colorectal cancer. The third objective of this work was motivated by evidence that common variation in certain genes correlates with hormone levels. Since genotype is constant, genotypic variation may act as a proxy measure for lifetime exposure to steroid hormones. A candidate gene approach was selected to address whether or not common variants in genes involved in steroid production (CYP17) and estrogen metabolism (COMT) were linked with age at onset of colon cancer among a cohort of confirmed Lynch syndrome mutation carriers in Newfoundland and Labrador (n = 153). This cohort experiences a dramatic predilection to colon and certain extracolonic cancers. The variant allele in CYP17 was linked with earlier age at colon cancer onset and overall increased risk of colon cancer (HR: 3.83). The COMT variant was not related to the outcomes in this thesis.
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 | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».