Colorectal cancer is a leading cause of cancer deaths, and both genetics and environmental factors influence colorectal cancer risk. In cancer tissues, a specific genetic variant is linked to higher levels of Fusobacterium nucleatum, a bacterium that can promote colorectal cancer growth and resistance to anti-cancer therapy, new research has shown.

The findings, published in Cell Host & Microbe, suggest that genetic factors can influence tumor-associated microbes, offering insights into colorectal cancer progression and potential therapeutic targets.

Previous studies indicate that certain bacteria, including Fusobacterium nucleatum, are more abundant in tumor tissues and can promote cancer growth. While a person’s genetics is known to affect the gut microbiota, its impact on tumor-associated bacteria in colorectal cancer is not well understood.

Researchers led by Jing Yu at Sun Yat-sen University in Guangzhou, China, analyzed tumor and adjacent normal tissues from 243 people with colorectal cancer to investigate the relationship between human genetic variants and the presence of specific bacteria in tumors.

Genetic associations

Certain variants were linked to the abundance of bacteria such as Fusobacterium, Parvimonas and Streptococcus in tumor tissues. In particular, the variant rs2355016, located in the KCNJ11 gene, was associated with higher levels of Fusobacterium and poor clinical outcomes, including larger and more aggressive tumors.

Fusobacterium nucleatum was the most common species of Fusobacterium in colorectal cancer tumors, and its abundance was linked to the variant rs2355016. Patients with this variant had higher levels of F. nucleatum, which were associated with tumor size. 

The researchers also found that this genetic variant led to lower expression of the KCNJ11 gene in tumor cells, which in turn increased the binding of F. nucleatum to the cells, promoting tumor growth. 

Boosting tumor-associated bacteria

Reducing the expression of the KCNJ11 gene in mouse models of colorectal cancer increased the growth of tumors and the presence of F. nucleatum in tumor tissues. Downregulating KCNJ11 also boosted the expression of a molecule on the surface of tumor cells that facilitated the binding of F. nucleatum to these cells.

The findings suggest that the role of KCNJ11 in regulating tumor progression can be influenced by a person’s genetics and tumor-associated microbes, the researchers say. However, they add, the exact mechanisms and the generalizability of the findings across different populations require further research.

“This study also deepens our understanding of the complex nature of host-microbiota interactions and provides insights into the role of intratumoral microbiota in other cancers,” the authors say.