Dataset Information

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

ABSTRACT: 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. 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. 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 Pheterogeneity < .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. Risk factor profiles may differ for CRC arising from different molecular pathways.

SUBMITTER: Wang L

PROVIDER: S-EPMC7791624 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Wang Liang L He Xiaosheng X Ugai Tomotaka T Haruki Koichiro K Lo Chun-Han CH Hang Dong D Akimoto Naohiko N Fujiyoshi Kenji K Wang Molin M Fuchs Charles S CS Meyerhardt Jeffrey A JA Zhang Xuehong X Wu Kana K Chan Andrew T AT Giovannucci Edward L EL Ogino Shuji S Song Mingyang M

JNCI cancer spectrum 20201007 1

<h4>Background</h4>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.<h4>Methods</h4>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 <i>BRAF</i> and <i>KRAS</i> mutations ...[more]

PMID: 33442661

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Dataset Information

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

Publications

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

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