Rheumatoid Arthritis genes associated with reduced risk of colorectal cancer development, suggests study

A recent study published in the Journal of Cellular and Molecular Medicine highlighted the complex relationship between rheumatoid arthritis (RA) and cancer. Despite the ongoing debate about whether RA increases the risk of malignancy, this research suggests that RA might actually reduce the risk of certain malignancy like colorectal cancer.

The study utilized Mendelian randomization (MR) analysis to investigate the potential causal relationship between RA and various cancers. The research employed a multi-faceted investigation to explore the overall relationship between RA and cancer (referred to as "pan-cancer" analysis). The results found a negative correlation between RA and pan-cancer (p = 0.008) which suggests the role of RA which might actually lower the overall risk of cancer development. An intermediate MR analysis was set out to understand how immune-mediated inflammation influences cancer risk. The autoimmune traits were identified as the main mediating variable which indicated the heightened activity of immune system in RA patients and its protective role against cancer development.

Further validation from a large-scale meta-analysis compared the standardized incidence rate (SIR) of malignancy in RA patients against the general population. This analysis confirmed that RA patients had a reduced likelihood of developing colorectal cancer with an SIR of 0.69 (95% CI 0.53–0.85). This meant that RA patients were 31% less likely to develop colorectal cancer when compared to the general population.

The study performed a detailed pan-cancer analysis of genes associated with RA which were identified through the MR analysis. This was to uncover the genetic mechanisms behind the observed protective effect, where one gene stood out. IL6R showed the highest correlation with immune cells in colorectal cancer. High expression of RA-related genes, the IL6R, was negatively correlated with colon adenocarcinoma.

IL6R is known for its role in the immune response regulation where this study suggests that IL6R and other RA-related genes might enhance the ability of immune system to target and destroy cancer cells in the colon. This study provides strong evidence that RA is associated with a reduced risk of colorectal cancer and the protective effect is primarily driven by immune-mediated inflammation where IL6R plays a crucial role. These findings open new opportunities for understanding the underlying interplay between autoimmune diseases and cancer which could lead to novel therapeutic strategies.

Source:

Li, Q., Zhou, L., Xia, D., & Wang, J. (2024). Rheumatoid arthritis reduces the risk of colorectal cancer through immune inflammation mediation. In Journal of Cellular and Molecular Medicine (Vol. 28, Issue 13). Wiley. https://doi.org/10.1111/jcmm.18515