Inflammatory potential of the diet and colorectal tumor risk in persons with Lynch syndrome

Abstract

Persons with Lynch syndrome (LS) have high lifetime risk of developing colorectal tumors (CRTs) because of a germline mutation in one of their mismatch repair (MMR) genes. An important process in the development of CRTs is inflammation, which has been shown to be modulated by diet. We aimed to investigate the association between the inflammatory potential of the diet and the risk of CRTs in persons with LS. We used the dietary intake of 457 persons with LS from a prospective cohort study to calculate the adapted dietary inflammatory index (ADII). The ADII was split into tertiles in which the highest tertile reflects the most proinflammatory potential of the diet. Cox proportional hazard models, with robust sandwich variance estimates to adjust for dependency within families, were used to calculate HRs and 95% CIs of CRTs by ADII tertile. HRs were adjusted for age, smoking status, and education level, and number of colonoscopies as a time-dependent variable. A potential effect measure modification was explored by stratifying the results by mutated MMR gene, sex, and a history of CRTs. We performed sensitivity analyses by repeating the analyses in non-nonsteroidal anti-inflammatory drug (NSAID) users ( = 315). During a median follow-up time of 59 mo, 200 participants (43.8%) developed CRTs. No significant association was shown between highest compared with lowest ADII tertiles (HR for highest compared with lowest tertiles: 1.37; 95% CI: 0.80, 2.34). Stratification by mutated MMR gene, sex, and CRT history did not show significantly differential associations (-interactions ≥ 0.64). In non-NSAID users, an HR of 1.60 (95% CI: 0.88, 2.93) for highest compared with lowest tertiles was shown. No significant effect modification was shown in this group either (-interactions ≥ 0.24). A proinflammatory potential of the diet does not seem to be significantly associated with CRT risk in persons with LS.

Systematic review and meta-analysis of diet quality and colorectal cancer risk: is the evidence of sufficient quality to develop recommendations?

“…All studies included in our meta-analysis used the latest version of the DII, comprising 18-45 food components validated based on their association with five inflammatory biomarkers of interleukins (IL)-1b, IL-4, IL-6, IL-10, plus tumor necrosis factor alpha (TNF-a) (Shivappa et al 2014). In contrast to the overall pooled risk estimates, three studies in our meta-analysis reported a null effect of low DII scores on CRC risk (Boden et al 2019;Brouwer et al 2017;Liu et al 2017). However, a closer look at the methods used in these studies revealed that the inconsistency probably resulted from a lack of data on food parameters with antiinflammatory effects in the DII calculation, a failure to adjust for some confounders (e.g., history of NSAID use) (Boden et al 2019), and reduced generalizability due to the study population (e.g.…”

“…Assessments of the impact of diet quality, as quantified by diet indices, on CRC risk have yielded inconclusive results (Haslam et al 2017;Jones et al 2017;Hoffmann 2015a, 2015b). Some studies have demonstrated no association between CRC risk and the DII (Boden et al 2019;Brouwer et al 2017;Liu et al 2017;Tabung et al 2017), MDS (Fasanelli et al 2017;Jafari Nasab et al 2019;Lavalette et al 2018;Petimar et al 2018;Torres Stone et al 2017), or HEI (Lavalette et al 2018), whereas a large cohort study reported an approximate 30% risk reduction in CRC when people consumed a diet constituting a low DII, as an indicator of less inflammatory and high diet quality (Tabung et al 2018). Similarly, consuming diet components that yield a high score of DASH, HEI (Erben et al 2018) and MDS (Jones et al 2017), are likely to reduce CRC risk.…”

Perspective: The Dietary Inflammatory Index (DII)—Lessons Learned, Improvements Made, and Future Directions

“…We wrote a letter to the editor of the American Journal of Clinical Nutrition pointing out the methodologic improvements entailed in the new DII compared with the older version (125). Despite this, the authors persisted in using their adaptation of the old, now defunct version of the DII in a recent study examining the association between the inflammatory potential of the diet and risk of colorectal cancer in individuals with Lynch syndrome (127). Furthermore, all of the corroborative evidence cited is based on references to the new DII, not the one on which their Adapted-DII was based (56,(128)(129)(130)(131)(132)(133).…”

“…Furthermore, all of the corroborative evidence cited is based on references to the new DII, not the one on which their Adapted-DII was based (56,(128)(129)(130)(131)(132)(133). When they were touting the advantage of the Adapted-DII in their own study (127), evidently they were comparing results to the old, now defunct version DII. They also arbitrarily omitted 3 of the proinflammatory parameters and 14 others that were not estimable from their FFQ.…”

Dietary Inflammatory Index and Non-Communicable Disease Risk: A Narrative Review

“…We now know that inflammation is not a single cancer-related mechanism. Rather, it is a substrate on which other mechanisms operate, including oxidative and nitrative DNA damage, changes in gene expression and genetic instability, insulin resistance, blunted immune response, neural signaling, and vascular dysfunction [55,56,57,58,59,60,61,62,63,64,65,66,67]. The DII concept arose in the context of conducting cancer research to address the conceptual and methodologic gaps between the burgeoning fields of inflammation-related and dietary research.…”