How human genetics and intratumoral microbiota affect colorectal cancer microbiologystudy

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. While scientists believe that gut microbiota play an important role in both the onset and progression of CRC, emerging evidence points to the significance of intratumoral microbiota—microbiota inside tumors—in CRC progression.

Nevertheless, little research has been done on the impact of genetics on intratumoral microbiota in CRC patients.

Now, a recent study by the Guangzhou Institutes of Biomedicine and Health of the Chinese Academy of Sciences, in collaboration with Sun Yat-sen University and the University of Hong Kong, has focused on this relationship and its effect on CRC.

The study shows that the single-nucleotide polymorphism (SNP) rs2355016—a tiny DNA change that some people carry—affects how intratumoral microbiota adhere to tumor cells, promoting CRC progression. These findings were published in Cell Host & Microbe.

For this study, the researchers conducted a comprehensive evaluation of the connection between host genetics and intratumoral microbiota in 748 CRC patients. Host genetics were analyzed using the Asian Screening Array, while intratumoral microbiota were identified through 16S rRNA sequencing. Genome-wide association study analyses assessed the relationships between SNPs and intratumoral microbiota.

The results indicated that SNP rs2355016, which is located in the intronic region of the KCNJ11 gene (ATP-sensitive inward rectifier potassium channel 11), was significantly correlated with levels of F. nucleatum—an anaerobic bacterium that mainly lives in the human mouth and gut—in CRC tissues.

Additionally, analyses of the expression Quantitative Trait Locus (eQTL) and protein Quantitative Trait Locus (pQTL) regions, i.e., regions of chromosomal DNA, showed that the A allele of SNP rs2355016 downregulates the expression of KCNJ11 in CRC cells. This downregulation may increase the presence of Gal-GalNAc on the surface of tumor cells. The increased Gal-GalNAc interacts with Fap2, enhancing the adhesion and invasion of F. nucleatum, ultimately contributing to CRC growth.

These findings enhance our understanding of CRC progression and may inform the development of effective treatments aimed at curbing tumor growth driven by intratumoral microbiota. Furthermore, this study broadens our understanding of the complex dynamics between host and microbiota interactions, shedding light on the role of intratumoral microbiota in other types of cancer.