Vitamin C Intake and Colorectal Cancer Survival According to KRAS and BRAF Mutation: a Prospective Study in Two US Cohorts

Overview

Journal Br J Cancer

Specialty Oncology

Date 2023 Sep 29

PMID 37775523

Authors

Shanshan Shi

Kai Wang

Tomotaka Ugai

Marios Giannakis

Jules Cazaubiel

Andrew T Chan

Edward L Giovannucci

Jonathan A Nowak

Jeffrey A Meyerhardt

Shuji Ogino

Mingyang Song

Affiliations

Soon will be listed here.

Abstract

Background: The associations of vitamin C intake with colorectal cancer (CRC) survival according to tumour KRAS or BRAF mutation status remain unclear.

Methods: We used the inverse probability weighted multivariable Cox proportional hazards regression model to calculate the hazard ratio (HR) of mortality, and spline analysis to evaluate the dose-response relationship in the Nurses' Health Study and Health Professionals Follow-up Study. We also assessed SLC2A1 mRNA expression according to KRAS or BRAF mutation in the TCGA database.

Results: During an average of 12.0 years of follow-up, we documented 2,096 CRC cases, of which 703 cases had KRAS and BRAF mutation data. The association between total vitamin C intake and CRC-specific mortality suggestively differed according to KRAS or BRAF mutation status (P = 0.04), with the multivariable HR (95% CI) per 400 mg/day increase in vitamin C intake for CRC-specific mortality of 1.07 (0.87-1.32, P = 0.52) in cases with both wild type and 0.74 (0.55-1.00, P < 0.05) in cases with either KRAS or BRAF mutant type. TCGA analysis showed a higher mRNA SLC2A1 expression in KRAS or BRAF-mutated tumours than in wild-type tumours (P = 0.02).

Conclusion: Our findings support the laboratory evidence for a potential benefit of vitamin C for CRC patients with KRAS or BRAF mutated tumours.

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