Association Between Inflammatory Diet Pattern and Risk of Colorectal Carcinoma Subtypes Classified by Immune Responses to Tumor

Abstract

Background & Aims Dietary patterns affect systemic and local intestinal inflammation, which have been linked to colorectal carcinogenesis. Chronic inflammation can interfere with the adaptive immune response. We investigated whether the association of a diet that promotes intestinal inflammation with risk of colorectal carcinoma was stronger for tumors with lower lymphocytic reactions than tumors with higher lymphocytic reactions. Methods We collected data from the molecular pathological epidemiology databases of 2 prospective cohort studies: the Nurses’ Health Study (since 1976) and the Health Professional Follow-up Study (since 1986). We used duplication-method time-varying Cox proportional cause-specific hazards regression to assess the association of empirical dietary inflammatory pattern (EDIP) score (derived from food frequency questionnaire data) with colorectal carcinoma subtype. Foods that contribute to high EDIP scores include red and processed meats, refined grains, carbonated beverages, and some vegetables; foods that contribute to low EDIP scores include beer, wine, coffee, tea, yellow and leafy vegetables, and fruit juice. Colorectal tissue samples were analyzed histologically for patterns of lymphocytic reactions (Crohn’s-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, and tumor-infiltrating lymphocytes). Results During follow up of 124,433 participants, we documented 1311 incident colon and rectal cancer cases with available tissue data. The association between the EDIP and colorectal cancer risk was significant (Ptrend = .02), and varied with degree of peritumoral lymphocytic reaction (Pheterogeneity < .001). Higher EDIP scores were associated with increased risk of colorectal cancer with an absent or low peritumoral lymphocytic reaction (highest vs lowest EDIP score quintile hazard ratio = 2.60; 95% CI, 1.60–4.23; Ptrend < .001) but not risk of tumors with intermediate or high peritumoral lymphocytic reaction (Ptrend > .80). Conclusions In a prospective cohort study, we associated inflammatory diets with a higher risk of colorectal cancer subtype that contains little or no peritumoral lymphocytic reaction. These findings suggest that diet-related inflammation might contribute to development of colorectal cancer, by suppressing the adaptive anti-tumor immune response.

Colorectal Cancers: An Update on Their Molecular Pathology

“…A recent study demonstrated an association of pro-inflammatory diets such as red and processed meats, with a higher risk for CRC subtypes with absent/low-lymphocytic reaction than CRC subtypes with high-lymphocytic reaction in the tumor microenvironment. The pro-inflammatory diet-associated CRC subtype was enriched in MSS, CIMP-low/negative, and BRAF wild-type phenotype [ 112 ]. The expression level of CD274 in tumors is inversely associated with the density of FOXP3-positive regulatory T cells, revealing the potential interactions between the immune checkpoint pathway and the host immunity in colorectal carcinogenesis [ 113 ].…”

Personalized Nutrition—Genes, Diet, and Related Interactive Parameters as Predictors of Cancer in Multiethnic Colorectal Cancer Families

“…Therefore, gene polymorphisms in the OCM pathway can decrease supplies of metabolites and cofactors, such as folate and B-vitamins, increasing the risk of CRC. Nutrients that can act as methyl donors related to these genes, including folate (vitamin B9) and vitamin B12, play integral roles in the phenotypic expression of related gene mutations in methylation pathways [ 28 , 29 , 30 , 31 , 38 , 39 ].…”

Gut microbiome meta-analysis reveals dysbiosis is independent of body mass index in predicting risk of obesity-associated CRC

“…Specifically, when B. pseudocatenulatum (CECT 7765) was given orally to obese mice, it increased Tregs and reduced pro-inflammatory cytokines (IL-17A and TNF-a), which further supports the hypothesis that certain species may protect against chronic inflammation and development of CRC (51). In reports measuring dietary inflammatory factors (empirical dietary inflammatory pattern), individuals with higher inflammatory scores had fewer tumor-associated adaptive anti-tumor immune cells suggesting immune evasion (65). Moreover, using this same approach, higher inflammatory scores were associated with higher tumor-associated F. nucleatum in CRC (66).…”