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About this Publication
Title
Intake of Dietary Fruit, Vegetables, and Fiber and Risk of Colorectal Cancer According to Molecular Subtypes: A Pooled Analysis of 9 Studies.
Pubmed ID
32816852 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Cancer Res. 2020 Oct 15; Volume 80 (Issue 20): Pages 4578-4590
Authors

Hidaka A, Harrison TA, Cao Y, Sakoda LC, Barfield R, Giannakis M, Song M, Phipps AI, Figueiredo JC, Zaidi SH, Toland AE, Amitay EL, Berndt SI, Borozan I, Chan AT, Gallinger S, Gunter MJ, Guinter MA, Harlid S, Hampel H, Jenkins MA, Lin Y, Moreno V, Newcomb PA, Nishihara R, Ogino S, Obón-Santacana M, Parfrey PS, Potter JD, Slattery ML, Steinfelder RS, Um CY, Wang X, Woods MO, Van Guelpen B, Thibodeau SN, Hoffmeister M, Sun W, Hsu L, Buchanan DD, Campbell PT, Peters U

Abstract

Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of BRAF-mutated tumors [OR 4th vs. 1st quartile = 0.82 (95% confidence interval, 0.65-1.04)] but not BRAF-wildtype tumors [1.09 (0.97-1.22); P difference as shown in case-only analysis = 0.02]. This difference was observed in case-control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative, BRAF-wildtype, and KRAS-wildtype tumors (Ptrend range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive, BRAF-mutated, or KRAS-mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported. SIGNIFICANCE: These analyses by colorectal cancer molecular subtypes potentially explain the inconsistent findings between dietary fruit or fiber intake and overall colorectal cancer risk that have previously been reported.

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