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Antibiotic use and colon cancer: more evidence of link

A Swedish population study published this month in the Journal of the National Cancer Institute adds to the body of evidence that shows an association between antibiotic use and an increased risk of developing colon cancer. Evidence from a large Scottish study published earlier this year found that a history of antibiotic use in people under 50 appeared to increase the risk of developing colon cancer by 49%.

The Swedish study looked at data from over 40,000 colorectal cancer patients and 200,000 cancer-free control individuals over the period 2005-2016 (11 years). Antibiotic use was classified as:

• no use (no reported use of antibiotics during the study period)

• low (use during a period of 1-10 days)

• moderate (11-60 days)

• high (61-180 days)

• very high (>180 days)

Moderate use of antibiotics increased the risk for proximal (right-sided) colon cancer by 9%, and very high antibiotic use increased a person’s risk by 17%. The association of antibiotic use and rectal cancer was quite different (inverse association), where risk was reduced by 4% with moderate use and 9% with very high use – an association that was only found in women.

When the analysis was separated by tumor site, the dose-response relationship between antibiotic use and CRC risk was mostly confined to the right side of the colon for moderate and very high use compared to no use. Associations were almost non-existent for distal (left-sided) colon cancer. By observing association by tumour subsites, any use vs. no use of antibiotics showed a risk gradient along the colon and rectum, with the strongest positive association in the ascending colon all the way to an inverse association in the rectum.

Interestingly, for a class of antibiotic, methenamine hippurate, a urinary tract antibiotic with no known effects on gut microbiota, there were no associations found with overall risk of CRC.

Discussion

The study findings demonstrate a strong association between antibiotics use and higher risk of right-sided colon cancer, a finding consistent with previous study findings. The lack of any association between the use of methenamine hippurate, a locally acting antibiotic in the urinary tract and CRC risk provides indirect support for dysbiosis of the gut microbiome as an underlying mechanism for the link between antibiotic use and colon cancer development.

The observed gradient of risk along the colorectal “continuum” is consistent with the existence of a high microbial activity in the proximal colon, and a decreasing concentration of short-chain fatty acids along the colon (the main by-products produced by the gut bacteria in the large intestine).

This indicates higher bacterial impact and fermentation in the right side of the colon compared with the left side of colon. It is important to note that associations between antibiotics use and right-sided colon cancer began at the very lowest level of antibiotic use, underlining the importance of judicious clinical use.

Take away message:

A recent study revealed a robust association between antibiotics use and higher resulting incidence of proximal (right-sided) colon cancer and an inverse association for rectal cancer in women. These findings support previous findings and provide deeper insight into the association between antibiotics and site-specific colorectal cancer development.

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