C-reactive Protein and Future Risk of Clinical and Molecular Subtypes of Colorectal Cancer

Abstract

Background: Inflammation has been implicated in colorectal cancer (CRC) etiology, but the relationship between C-reactive protein (CRP) and CRC risk is unclear. We aimed to investigate the association between pre-diagnostic plasma CRP concentrations and the risk of clinical and molecular CRC subtypes. Methods: We used prospectively collected samples from 1010 matched CRC case-control pairs from two population-based cohorts in Northern Sweden, including 259 with repeated samples. Conditional logistic regression and linear mixed models were used to estimate relative risks of CRC, including subtypes based on BRAF and KRAS mutations, microsatellite instability status, tumor location, stage, lag-time, and (using unconditional logistic regression) BMI. Results: CRP was not associated with CRC risk, regardless of clinical or molecular CRC subtype. For participants with advanced tumors and blood samples <5 years before diagnosis, CRP was associated with higher risk (odds ratio per 1 unit increase in natural logarithmtransformed (ln) CRP 1.32, 95% CI 1.01-1.73). CRP levels increased over time, but average time trajectories were similar for cases and controls (P interaction =0.19). Conclusions: Our results do not support intertumoral heterogeneity as an explanation for previous inconsistent findings regarding the role of CRP in CRC etiology. The possible association in the subgroup with advanced tumors and shorter follow-up likely reflects undiagnosed cancer at baseline. Impact: Future efforts to establish the putative role of chronic, low-grade inflammation in CRC development will need to address the complex relationship between systemic inflammatory factors and tumor microenvironment, and might consider larger biomarker panels than CRP alone.

Pre-diagnostic C-reactive protein concentrations, CRP genetic variation and mortality among individuals with colorectal cancer in Western European populations

“…The positive association with pre-diagnostic CRP was observed for colon but not for rectal cancer, and among men but not women. In the most recent investigation, a populationbased nested case-control study from Northern Sweden, CRP concentrations were not related to subsequent risk of CRC, regardless of CRC location, stage or molecular subtype [9]. In the European Prospective Investigation into Cancer and Nutrition (EPIC), we previously observed that elevated circulating CRP concentrations were associated with a higher risk of colon but not rectal cancer and a higher risk of colon cancer was particularly observed in men but not in women [10].…”

Inflammation-Immunity-Nutrition Score: A Novel Prognostic Score for Patients with Resectable Colorectal Cancer

“…10 Prognostic scores derived from the combination of several of C-reactive protein (CRP), hsCRP, LYM, and ALB have been constructed and presented better performance than individual indicators. [11][12][13] The high-sensitivity modified Glasgow Prognostic Score (hs-mGPS: the combination of hsCRP and ALB), hsCRP/ALB, and prognostic nutrition index (PNI: the combination of LYM and ALB) have been proposed as predictors for survival of cancer patients. [14][15][16][17][18] A comparative study reported that the prognostic value of Glasgow Prognostic Score (GPS: the combination of CRP and ALB) was better than those of CRP and ALB in patients with hepatocellular carcinoma.…”