Umea, Sweden—A nationwide analysis of more than 40,00 colorectal cancer cases in Sweden determined a “robust association” between use of antibiotics and proximal colon cancer.

The report in the Journal of the National Cancer Institute notes that those findings are consistent with previous investigations. The Umeå University–led research also confirms an inverse association between antibiotics use and rectal cancer risk, which appears to occur primarily in women.

Researchers advise that antibiotic use might increase colorectal cancer (CRC) risk by altering the gut microbiota.

The study employed complete-population data, extracted from Swedish national registers for 2005-2016. Included were 40,545 CRC cases and 202,720 controls.

“Using the full dataset, we found a positive association between more frequent antibiotics use and CRC, excluding antibiotics prescribed within 2 years of diagnosis attenuated results toward the null,” the authors write. “In site-specific analyses, excluding the 2-year washout, the positive association was confined to the proximal colon (adjusted odds ratio for very high use vs. no use = 1.17, 95% confidence interval = 1.05 to 1.31).”

Researchers report that quinolones and sulfonamides and/or trimethoprims were positively associated with proximal colon cancer but note that a more general inverse association across antibiotics classes was observed for rectal cancer.

“This register-based study covering the entire population of Sweden found a robust association between antibiotics use and higher risk of proximal colon cancer and an inverse association with rectal cancer in women,” the authors conclude. “This study strengthens the evidence from previous investigations and adds important insight into site-specific colorectal carcinogenesis.”

Background information in the articles points out that CRC is a multifactorial disease that can involve lifestyle and medical risk factors. “A continued effort to identify risk factors for CRC is imperative because reducing even minor risk factors at the population level could have a substantial impact on the incidence of CRC,” researchers emphasize.

Much of their focus was on the composition and function of the gut microbiome, which is believed to have a role in CRC development.

“Many established CRC risk factors, including excess body fat and dietary factors, could alter the gut microbiome,” the study notes. “However, use of antibiotics can have a more disruptive effect.

For example, treatment with antibiotics can alter the microbial balance in the gut resulting in intestinal overgrowth of toxin-producing Clostridium difficile bacteria, causing diarrhea and inflammation. Antibiotic-induced dysbiosis may disrupt the anti-inflammatory effects of some microbiota and increase pathogenic bacteria, influencing CRC tumorigenesis.”

They add that a positive association between antibiotic use and CRC has been identified but that most studies “had limited information or insufficient power for extensive analyses of aspects such as type, dose, or duration of antibiotics and tumor stage and site.”

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