Background/Aim: Gut microbiota plays an important role in colorectal cancer (CRC) and its composition in CRC patients can be influenced by ethnicity and tumour genomics. Herein, the aim was to study the possible associations of ethnicity and gene mutations with the gut microbiota in CRC patients. Materials and Methods: Bacterial composition in stool samples of 83 CRC patients and 60 controls from Iran and Finland was studied by 16S rRNA gene sequencing. The association of gut microbiota composition with CRC, host mutations in KRAS, NRAS and TP53, and ethnicity analysed. Results: Beta diversity analysis indicated significant differences between the Iranian and Finnish gut microbiota composition, in both controls and patients' groups. The Iranian controls had higher abundance of Prevotella and lower abundance of Bacteroides compared to the Finnish controls, while the Finnish patients had higher abundance of Clostridium compared to Iranian patients. Abundance of Ruminococcus was higher in patients compared to the controls. Higher abundances of Herbaspirillum, Catenibacterium and lower abundances of Barnesiella were associated with mutations in NRAS, TP53, and RAS respectively. Conclusion: A possible link of host gene mutations with gut bacterial composition is suggested. The gut microbiota plays an integral role in the regulation of different gastrointestinal functions. There is increasing evidence that the gut microbiota not only contributes to the initiation and progression of colorectal cancer (CRC) but also influences the host response to cancer treatment, especially chemo-and immunotherapy (1). In addition to its regional effect in the gastrointestinal tract, the gut microbiota also affects distant organs via its role in shaping the immune system and host metabolism (2). Diet, lifestyle and ethnicity are among the main determinants of microbiota composition, and changes in diet associated with a modern lifestyle have been linked to microbiota-mediated cancer risk (3). The host genetic variation is also known to effect bacterial composition (4), although this area has not been investigated extensively. The host genetics is reported to strongly influence the abundance of gut Christensenellaceae (5), the bacteria associated with low body mass index. The Bifidobacterium abundance has been linked with a variation in the lactose tolerance gene LCT loci (6, 7). On the other hand, tumour genome is reported to be a factor modulating colonization of certain bacteria around colorectal tumour tissue (8, 9). A high abundance of Fusobacterium has been reported to be associated with CpG island methylator phenotype (CIMP), microsatellite instability (MSI) and mutations in CHD7/8 (10). However, the associations between tumour mutations and gut microbiota composition remain poorly understood. The association of the gut microbiota composition with different disease states makes them useful as potential diagnostic markers of health and disease (11). Recent largescale studies have however demonstrated that ethnicity (12) and geogra...

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Colorectal cancer (CRC) rated among the three most diagnosed cancers and the fourth main cause of death worldwide. CRC is a curable cancer provided to be diagnosed at its early-stage. Colonoscopy, stool and blood-based tests are in use for CRC diagnosis/screening. Due to low patient compliance, low specificity and high rate of false results, more reliable methods with desired level of detection accuracy and high patients’ compliance are highly demanded. Detecting hotspot mutations in stool DNA emerged as a robust noninvasive alternative, but due to the different genetic background of various populations and hence varied mutation spectrum/prevalence, prior assessment of CRC mutations in the population is essential. Here, we have evaluated stool DNAs from CRC patients and controls using a NGS based 22 genes panel. Hotspot mutations in NRAS, FGFR3, SMAD4 and TP53 genes had higher prevalence among the CRC patients compare to normal controls. Patients were followed up in their post-surgical period. Six of them (12%) with TP53 mutations (2 patients had NRAS mutation as well) were died of cancer. Those harboring mutations in TP53 and/or NRAS would be regarded as high risk and should be provided with special care.