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Risk Factors and Incidence of Colorectal Cancer According to Major Molecular Subtypes

BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease that can develop via 3 major pathways: conventional, serrated, and alternate. We aimed to examine whether the risk factor profiles differ according to pathway-related molecular subtypes. METHODS: We examined the association of 24 risk fa...

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Detalles Bibliográficos
Autores principales: Wang, Liang, He, Xiaosheng, Ugai, Tomotaka, Haruki, Koichiro, Lo, Chun-Han, Hang, Dong, Akimoto, Naohiko, Fujiyoshi, Kenji, Wang, Molin, Fuchs, Charles S, Meyerhardt, Jeffrey A, Zhang, Xuehong, Wu, Kana, Chan, Andrew T, Giovannucci, Edward L, Ogino, Shuji, Song, Mingyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791624/
https://www.ncbi.nlm.nih.gov/pubmed/33442661
http://dx.doi.org/10.1093/jncics/pkaa089
Descripción
Sumario:BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease that can develop via 3 major pathways: conventional, serrated, and alternate. We aimed to examine whether the risk factor profiles differ according to pathway-related molecular subtypes. METHODS: We examined the association of 24 risk factors with 4 CRC molecular subtypes based on a combinatorial status of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and BRAF and KRAS mutations by collecting data from 2 large US cohorts. We used inverse probability weighted duplication-method Cox proportional hazards regression to evaluate differential associations across subtypes. RESULTS: We documented 1175 CRC patients with molecular subtype data: subtype 1 (n = 498; conventional pathway; non-MSI-high, CIMP-low or negative, BRAF-wild-type, KRAS-wild-type), subtype 2 (n = 138; serrated pathway; any MSI status, CIMP-high, BRAF-mutated, KRAS-wild-type), subtype 3 (n = 367; alternate pathway; non-MSI-high, CIMP-low or negative, BRAF-wild-type, KRAS-mutated), and subtype 4 (n = 172; other marker combinations). Statistically significant heterogeneity in associations with CRC subtypes was found for age, sex, and smoking, with a higher hazard ratio (HR) observed for the subtype 2 (HR per 10 years of age = 2.64, 95% CI = 2.13 to 3.26; HR for female = 2.65, 95% CI = 1.60 to 4.39; HR per 20-pack-year of smoking = 1.29, 95% CI = 1.14 to 1.45) than other CRC subtypes (all P(heterogeneity) < .005). A stronger association was found for adiposity measures with subtype 1 CRC in men and subtype 3 CRC in women and for several dietary factors with subtype 1 CRC, although these differences did not achieve statistical significance at α  level of .005. CONCLUSIONS: Risk factor profiles may differ for CRC arising from different molecular pathways.