Dataset Information

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

ABSTRACT: Abstract

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 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 ?? level of .005.

Conclusions

Risk factor profiles may differ for CRC arising from different molecular pathways.

SUBMITTER: Wang L

PROVIDER: S-EPMC7791624 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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