Colorectal cancer is a leading cause of morbidity and mortality worldwide in both men and women. The gut microbiome is increasingly recognized as having an important role in human health and disease. Fusobacterium has been identified in former studies as a leading gut bacterium associated with colorectal cancer, but it is still not clear if it plays an oncogenic role. In the current study, fecal samples were collected prior to bowel preparation from participants of screening colonoscopy in the German BliTz study. Using 16S rRNA gene analysis, we examined the presence and relative abundance of Fusobacterium in fecal samples from 500 participants, including 46, 113, 110 and 231 individuals with colorectal cancer, advanced adenomas, non-advanced adenomas and without any neoplasms, respectively. We found that the abundance of Fusobacterium in feces was strongly associated with the presence of colorectal cancer (P-value < 0.0001). This was confirmed by PCR at the species level for Fusobacterium nucleatum. However, no association was seen with the presence of advanced adenomas (P-value = 0.80) or non-advanced adenomas (P-value = 0.80), nor were there any associations observed with dietary or lifestyle habits. Although a causal role cannot be ruled out, our observations, based on fecal microbiome, support the hypothesis that Fusobacterium is a passenger that multiplies in the more favorable conditions caused by the malignant tumor rather than a causal factor in colorectal cancer development.

Background: Smoking and alcohol increase risk for colorectal malignancies. However, colorectal cancer (CRC) is a heterogenic disease and associations with the molecular pathological pathways are unclear. Methods: This population-based case–control study includes 2444 cases with first-diagnosis CRC and 2475 controls. Tumour tissue was analysed for MSI (microsatellite instability), CIMP (CpG island methylator phenotype), BRAF (B-Raf proto-oncogene serine/threonine kinase gene) and KRAS (Kirsten rat sarcoma viral oncogene homologue gene) mutations. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for associations between alcohol and smoking and CRC molecular subtypes and pathways. Results: Current smoking showed higher ORs for MSI-high (OR = 2.79, 95% CI: 1.86–4.18) compared to MSS (OR = 1.41, 1.14–1.75, p-heterogeneity (p-het) = 0.001), BRAF-mutated (mut) (OR = 2.40, 1.41–4.07) compared to BRAF-wild type (wt) (OR = 1.52, 1.24–1.88, p-het = 0.074), KRAS-wt (OR = 1.70, 1.36–2.13) compared to KRAS-mut (OR = 1.26, 0.95–1.68, p-het = 0.039) and CIMP-high (OR = 2.01, 1.40–2.88) compared to CIMP-low/negative CRC (OR = 1.50, 1.22–1.85, p-het=0.101). Current smoking seemed more strongly associated with sessile serrated pathway (CIMP-high + BRAF-mut; OR = 2.39, 1.27–4.52) than with traditional pathway CRC (MSS + CIMP-low/negative + BRAF-wt; OR = 1.50, 1.16–1.94) and no association was observed with alternate pathway CRC (MSS + CIMP-low/negative + KRAS-wt; OR = 1.08, 0.77–1.43). No heterogeneity was observed in alcohol consumption association by molecular subtypes. Conclusions: In this large case–control study, smoking was more strongly associated with MSI-high and KRAS-wt CRC and with cases showing features of the sessile serrated pathway. Association patterns were less clear for alcohol consumption.

Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR = 0.42, 95% CI: 0.21–0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR = 1.53, 95% CI: 1.21–1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features.

Colorectal cancer (CRC) is a leading cause of morbidity and mortality. Post-CRC resection complications and lower quality of life (QoL) are associated with a lower long-term survival. Perioperative administration of probiotics/synbiotics might lower prevalence of side effects and improve QoL and survival among CRC patients. Medline, Web of Science, Cochrane database, Embase, and clinical trials registries were searched in January 2020. Altogether, 16 randomized placebo-controlled probiotic/synbiotic clinical trials that included patients undergoing CRC surgery and investigated postoperative complications and QoL side effects were found. Meta-analyses using random-effects model were performed on data from 11 studies to calculate the effects of probiotics/synbiotics on common CRC resection postoperative side effects and complications. Perioperative probiotics/synbiotics administration was associated with lower infection incidence (odds ratio [OR] = 0.34, P < 0.001), lower diarrheal incidence (OR = 0.38, P < 0.001), faster return to normal gut function (mean difference [MD] −0.66 days, P < 0.001), shorter postoperative antibiotics use (MD −0.64 days, P < 0.001), lower incidence of septicemia (OR = 0.31, P < 0.001), and shorter length of hospital stay (MD −0.41 days, P = 0.110). The results support the hypothesis that short-term perioperative administration of probiotics/synbiotics, which are easy to administer, have few side-effects, and are low cost compared with alternatives, might help to alleviate gastrointestinal symptoms and postoperative complications among CRC patients.

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.

Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. Dysbiosis in the gut microbiota may be associated with CRC. This systematic review focuses on differences in gut microbial community between people diagnosed with CRC or adenoma and healthy individuals using fecal samples, emphasizing non-invasive fecal microbiome models for CRC early diagnosis. Nineteen studies were identified in a systematic literature search of Pubmed, Web of Science and ScienceDirect. Several bacteria were reported to differ in abundance between CRC and adenoma cases and healthy controls, with Fusobacterium the most common. Fecal multi-bacterial predictive models used to distinguish CRC patients from healthy controls had reported areas under the receiver operating curve (AUCs) in external validation populations of 0.68–0.77. Though advanced sequencing techniques could in the future complement current non-invasive methods for CRC early detection, more studies with high statistical power, comparable and reproducible methods and external validation of predictive models are needed.