Does Appendectomy Increase Colorectal Cancer Risk?

A recent Chinese study raises the hypothesis that people who have undergone appendectomy, surgical removal of the appendix, may have increased colorectal cancer risk.

Compared with controls without appendectomy, the study found, after a 20-year follow-up , an increase in colorectal cancer risk of 73% .

The findings suggest that appendectomy may adversely affect the gut microbiome (microorganisms living in harmony with us in the intestines), supporting more careful consideration of surgical necessity. However, clinical significance is unclear, and larger studies in different populations are needed.

Study Details

Published on December 20, 2022 in Oncogene, the study suggests that appendectomy may alter the microbiome and promote colorectal carcinogenesis , or cancer formation, and that surgeons should "consider the need for appendectomy more carefully."

Dr. Charles Dinerstein, who was not involved, called the findings "intriguing" but said it was "too early" to determine clinical implications. The American Council on Science and Health medical director added, "I do not currently think patients who have undergone appendectomy need more intensive screening."

Growing evidence links intestinal microbes to CRC risk, and other research suggests that the appendix helps preserve gut microbiome diversity . Whether removal affects colorectal cancer (CRC) risk remains controversial.

The findings are interesting because the appendix has long been considered functionless and an evolutionary remnant.

A Three-Part Study

The researchers:

1. Analyzed 129,155 adults with and without appendectomy to assess a possible clinical link with CRC;
2. Used fecal metagenomic sequencing to compare the gut microbiome in appendectomy cases with matched controls; and
3. Studied an appendectomy CRC mouse model to explore mechanisms of appendectomy-associated carcinogenesis.

In approximately 130 thousand people, CRC risk in about 44 thousand appendectomy cases was compared with more than 85 thousand age- and sex-matched controls. Over 20 years, risk was 73% higher after appendectomy (adjusted hazard ratio [HR], 1.73; P<0.001). CRC risk and gut dysbiosis were more pronounced in adults older than 50 with an appendectomy history.

In part 2, 314 participants (157 appendectomy cases and 157 controls) provided stool samples for metagenomic analysis of stool samples and found substantial microbiome changes after appendectomy. These included Bacteroides vulgatus and Bacteroides fragilis , among 7 enriched CRC-associated bacteria , and Collinsella aerofaciens and Enterococcus hirae among five depleted beneficial bacteria.

Finally, appendectomy was performed in an experimental CRC mouse model to assess dysbiosis-related carcinogenesis. In this experiment, appendectomy promoted CRC formation by inducing gut dysbiosis.

Nevertheless, the study is observational and insufficient to establish causality.