Body size and risk of colorectal cancer molecular defined subtypes and pathways: Mendelian randomization analyses.
EBioMedicine
; 101: 105010, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38350331
ABSTRACT
BACKGROUND:
Obesity has been positively associated with most molecular subtypes of colorectal cancer (CRC); however, the magnitude and the causality of these associations is uncertain.METHODS:
We used Mendelian randomization (MR) to examine potential causal relationships between body size traits (body mass index [BMI], waist circumference, and body fat percentage) with risks of Jass classification types and individual subtypes of CRC (microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutations). Summary data on tumour markers were obtained from two genetic consortia (CCFR, GECCO).FINDINGS:
A 1-standard deviation (SD5.1 kg/m2) increment in BMI levels was found to increase risks of Jass type 1MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.46, 3.13; p-value = 9 × 10-5) and Jass type 2non-MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype CRC (OR 2.20, 95% CI 1.26, 3.86; p-value = 0.005). The magnitude of these associations was stronger compared with Jass type 4non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-wildtype CRC (p-differences 0.03 and 0.04, respectively). A 1-SD (SD13.4 cm) increment in waist circumference increased risk of Jass type 3non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-mutated (OR 1.73, 95% CI 1.34, 2.25; p-value = 9 × 10-5) that was stronger compared with Jass type 4 CRC (p-difference 0.03). A higher body fat percentage (SD8.5%) increased risk of Jass type 1 CRC (OR 2.59, 95% CI 1.49, 4.48; p-value = 0.001), which was greater than Jass type 4 CRC (p-difference 0.03).INTERPRETATION:
Body size was more strongly linked to the serrated (Jass types 1 and 2) and alternate (Jass type 3) pathways of colorectal carcinogenesis in comparison to the traditional pathway (Jass type 4).FUNDING:
Cancer Research UK, National Institute for Health Research, Medical Research Council, National Institutes of Health, National Cancer Institute, American Institute for Cancer Research, Brigham and Women's Hospital, Prevent Cancer Foundation, Victorian Cancer Agency, Swedish Research Council, Swedish Cancer Society, Region Västerbotten, Knut and Alice Wallenberg Foundation, Lion's Cancer Research Foundation, Insamlingsstiftelsen, Umeå University. Full funding details are provided in acknowledgements.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Proteínas Proto-Oncogênicas B-raf
Tipo de estudo:
Clinical_trials
/
Etiology_studies
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Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
EBioMedicine
Ano de publicação:
2024
Tipo de documento:
Article