In one part of a three-part analysis, researchers observed a 73% increase in CRC risk among appendectomy cases compared, with controls over a 20-year follow-up.
, published in Oncogene, suggests that appendectomy may promote colorectal tumorigenesis by influencing the gut microbiome and that surgeons should “more cautiously consider the necessity of appendectomy,” the authors concluded.
Charles Dinerstein, MD, who was not involved in the research, said that the findings are “intriguing,” but it’s “too soon to tell” what the potential clinical implications may be. For now, “I would not think those patients having undergone an appendectomy should have more intense screening,” said Dr. Dinerstein, medical director of the American Council on Science and Health.
A growing body of evidence suggests that microbes in the gut may play a role in CRC risk, and other research indicates that the appendix might play a role in maintaining the diversity of the gut microbiome. However, whether removing the appendix influences a person’s risk for CRC remains controversial.
In the current study, Feiyu Shi, MD, of The First Affiliated Hospital of Xi’an Jiaotong University, and colleagues sought to better understand a possible association between appendectomy and CRC risk.
The team performed a three-part study: (1) analyzed a population of 129,155 adults who had an appendectomy and those who did not to assess a possible clinical connection between appendectomy and CRC risk; (2) performed fecal metagenomics sequencing to evaluate characteristics of the gut microbiome in appendectomy cases versus matched normal controls without appendectomy; and (3) investigated a CRC mouse model with appendectomy to uncover a mechanism of appendectomy-induced colorectal tumorigenesis.
In the large epidemiological study, Dr. Shi and colleagues compared CRC risk in almost 44,000 appendectomy cases versus more than 85,000 age- and gender-matched nonappendectomy controls. The researchers found that, over the 20-year follow-up, the risk for CRC increased by 73% in appendectomy cases (adjusted hazard ratio, 1.73; P < .001). CRC risk and gut dysbiosis were more pronounced in adults older than 50 years with a history of appendectomy.
In the gut microbiome analysis, Dr. Shi’s team performed metagenomic sequencing on fecal samples from 314 participants – 157 appendectomy cases and 157 controls – and found significant alterations in the gut microbiome in appendectomy cases. The changes were characterized by enrichment of seven CRC-promoting bacteria, including Bacteroides vulgatus and Bacteroides fragilis, and depletion of five beneficial bacteria, including Collinsella aerofaciens and Enterococcus hirae.
Finally, to examine the influence of appendectomy on microbial dysbiosis and CRC tumorigenesis, Dr. Shi’s team performed an appendectomy or a sham procedure in a carcinogen-induced CRC mouse model and found that appendectomy appeared to promote CRC tumorigenesis by prompting gut dysbiosis.
Aasma Shaukat, MD, MPH, a gastroenterologist at NYU Langone Health, who was not involved in the research, urged caution in interpreting the findings, which “need confirmation in larger diverse cohorts.”
First, Dr. Shaukat explained, “the two groups are not comparable, even though [they were] matched for age and gender, and many known and unknown factors can explain the results.” For instance, information on which subjects underwent colon cancer screening is not known, which may explain differences.
Dr. Shaukat also cautioned that the researchers only profiled the microbiome in “a small group of individuals and a cross-sectional analysis is not sufficient to explain causation.”
The study had no commercial funding. Dr. Shi, Dr. Dinerstein, and Dr. Shaukat have no relevant conflicts of interest to report.
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