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Following Appendectomy, a Higher Incidence of Cancer Suggests an Immune-Function of Appendix

Casey Luskin

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In the past two weeks I’ve given three talks, and each time during the Q&A afterward, the same question came up from the audience: Does the appendix have a function, or as Darwinian evolutionists prefer, is the organ merely vestigial and therefore useless?

We’ve covered this issue many times before here on ENV. The answer is that the appendix is indeed functional. But a recent paper from PLOS One, “Association between Appendectomy and Subsequent Colorectal Cancer Development: An Asian Population Study,” sheds further light.

The study looked at over 75,000 patients who had undergone an appendectomy, and over 300,000 individuals who had not. The researchers investigated the incidence of colorectal cancer in both groups, and found that cancer rates were significantly higher in the group that had their appendix removed:

The overall colorectal cancer incidence was 14% higher in the appendectomy patients than in the comparison cohort (p <0.05): the highest incidence was observed for rectal cancer, and the lowest incidence was observed for cancer of the cecum-ascending colon for both cohorts. … Results of our study suggest that appendectomy in patients with appendicitis is likely associated with the development of colorectal cancer in the post-surgery period. … In this large retrospective cohort study with a 14-year follow-up, we found that patients who underwent an appendectomy had a 1.14-fold higher risk of colorectal cancer than the general population. The risk of cancer was 12.8-fold higher for older subjects compared with younger subjects. The results are reliable because the robustness of this relationship is supported by accurate diagnosis of both appendectomy and colorectal cancer with histological confirmation.

(Shih-Chi Wu, William Tzu-Liang Chen, Chih-Hsin Muo, Tao-Wei Ke, Chu-Wen Fang, Fung-Chang Sung, “Association between Appendectomy and Subsequent Colorectal Cancer Development: An Asian Population Study, PLOS One (February 24, 2015).)

What does this mean?

It could be that the surgical trauma of an appendectomy somehow increases your likelihood of developing colorectal cancer. Or, it could be that the causes of appendicitis (which of course leads to an appendectomy) can also be responsible for causing colorectal cancer. Perhaps appendicitis itself may even be a symptom of the cancerous conditions.

On the other hand, it could mean that the appendix performs an important immune function that helps prevent cancer, and people who have had their appendix removed lose this immune function, resulting in a higher rate of colorectal cancer.

The evidence from the paper suggests that all of the above are probably correct. They first explain how the appendix functions as a “safe house” for beneficial bacteria:

The vermiform appendix in humans is generally regarded as a vestigial structure. However, studies suggest that it serves as a “safe house” for biofilm formation to preserve and protect commensal bacteria needed for the epithelial mucosa in the colon. Biofilms are most abundant in the appendix, cecum and ascending colon (right side colon). The microbiota and biofilm in the large bowel might be changed after removal of the appendix (i.e., appendectomy). The role of appendectomy in inflammatory bowel disease is of concern, whether as a cause or a consequence. Patients who underwent appendectomy are associated with a 1.6- to 2.1-fold increased risk of Crohn’s disease but are less likely to have ulcerative colitis. The inflammatory responses differ in ulcerative colitis and appendicitis post-appendectomy. These conditions reflect an essential role of the appendix in the ecology of the microbiota and inflammation of the large bowel. Studies have rarely investigated whether the removal of the appendix changes the microbiota ecology and risk of colorectal cancer. In the present study, using longitudinal insurance claims data, we explored the link between patients who underwent appendectomy and the risk of subsequent colon cancer.

It is possible that the inflammation of the appendix itself (which requires the appendectomy) may result from colon cancer or from the same mechanisms that cause colon cancer. In that case, the association of appendicitis with colon cancer might not necessarily be due to the lack of an appendix (and the loss of its disease-preventing functions) but rather to some other disease-related cause. As the paper explains:

Appendicitis is thus considered the first manifestation of colon cancer, indicating a close relationship between the appendix and colon cancer. Our follow-up study also found that the colorectal cancer risk is higher for appendectomy patients than for the general population, although it is not as high as the rate found by Lai et al. The mechanism of cancer development associated with appendicitis may not be similar to the mechanism of cancer development associated with appendectomy.

However, it’s important to note that not everyone who has his appendix removed had appendicitis. Many people undergo an “incidental appendectomy,” where the appendix is removed for reasons that are separate from appendicitis, often during surgery for some other problem. And crucially, it turns out that these people too have a higher incidence of colorectal cancer:

This study also showed that patients who undergo incidental appendectomy are at a higher risk of subsequent colorectal cancer. It is possible that such patients could in fact have undetected cancer or have related high-risk conditions. To reduce misclassification, we excluded patients with colorectal cancer that was detected within 18 months after the appendectomy. Therefore, removal of an ordinary appendix is also associated with a higher incidence of subsequent colorectal cancer. This result may provide further evidences in the “safe house” hypothesis of the appendix.

So patients who didn’t have appendicitis or an immediate case of cancer, but did have their appendix removed, still showed a long-term increase in the incidence of colorectal cancer. This fact provides very strong evidence that the appendix has functions that help prevent cancer.

As we saw, the “safe house” function means that the appendix allows the growth of biofilms (thin sheets of bacteria) in the colon that help protect our cells in our large intestine (the colon). The authors seek to explain the relevance of these biofilms to fostering colon health and preventing cancer of the colon:

The biofilms of the large bowel are abundant in the appendix, cecum and right side colon. Impairing the growth of these biofilms may lead to dysbiosis [imbalance of bacteria] and may make the tissue vulnerable to inflammation, ultimately leading to the development of colorectal cancer. In the present study, the incidences of cancer among all colon sites are elevated after appendectomy. However, we found the lowest incidence of colorectal cancer in the cecum and the ascending colon in both cohorts. The previous abundant biofilm in cecum and ascending colon may be with lesser degree of dysbiosis and lesser declination in biofilm protective effect than in the rectum, which resulted in lower potential for malignancy. This finding may support the “safe house” hypothesis of biofilms in the appendix.

In other words, regardless of whether people had their appendix removed, the incidence of bowel cancer is lowest in regions that are closest to the appendix. The appendix and its nearby regions of the colon have lower incidences of cancer, but are rich in these biofilms. This suggests that the biofilms produced by the appendix and surrounding tissue help protect the large intestines from cancer — supporting what they call the “safe house hypothesis.”

Along with the clinical implications, the meaning of this study for the evolution debate is also noteworthy. Supposed vestigial organs have been a mainstay of the case for Darwinism. With research like this, following on earlier work along the same lines, that case grows weaker and weaker. If anything, Darwinian assumptions about vestigial organs have hindered our research into the functions for the appendix.

Image: � xixinxing / Dollar Photo Club.


Casey Luskin

Associate Director, Center for Science and Culture
Casey Luskin is a geologist and an attorney with graduate degrees in science and law, giving him expertise in both the scientific and legal dimensions of the debate over evolution. He earned his PhD in Geology from the University of Johannesburg, and BS and MS degrees in Earth Sciences from the University of California, San Diego, where he studied evolution extensively at both the graduate and undergraduate levels. His law degree is from the University of San Diego, where he focused his studies on First Amendment law, education law, and environmental law.



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