Exposure to antibiotics appears to be associated with the development of colon cancer, particularly in younger people, and could be contributing to the increase in early onset colorectal cancer (CRC) that is being documented, say UK researchers.
The team conducted a nested case-control study using data from primary care in Scotland, which involved almost 8000 cases of CRC and over 30,000 healthy controls.
The analysis suggests that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer (but not rectal) by 49%.
"To our knowledge, this is the first study to link antibiotic use with the growing risk of early onset colon cancer, a disease which has been increasing at a rate of at least 3% per year over the last two decades," said study presenter Sarah Perrott, a medical student at the University of Aberdeen, Scotland, UK.
"Junk food, sugary drinks, obesity, and alcohol are likely to have played a part in that rise, but our data stress the importance of avoiding unnecessary antibiotics, especially in children and young adults," Perrott said in a statement.
"We now want to find out if there is a link between antibiotic use and changes in the microbiome which can make the colon more susceptible to cancer especially in younger people," added senior author Leslie Samuel, MD, consultant oncologist at Aberdeen Royal Infirmary.
"It's a complex situation as we know that the microbiome can quickly revert to its previous state even when the bowel has been cleared out for a diagnostic procedure," Samuel continued.
The research was presented on July 2 at the ESMO World Congress on Gastrointestinal Cancer 2021.
Commenting for ESMO, Alberto Sobrero, MD, PhD, Medical Oncology Unit, Ospedale San Martino, Genoa, Italy, said that younger patients with colon cancer typically have a worse prognosis than older people because they are generally diagnosed later.
"Physicians are less likely to investigate a patient with abdominal discomfort for colon cancer if they are in their 30s than if they are in their 70s, and younger patients are not eligible for bowel cancer screening," he explained.
However, Sobrero believes it is "too early to say if excessive use of antibiotics could be a causative factor, and we need to understand more about the possible role of the microbiome in bowel cancer before we consider the impact of antibiotics on the intestinal flora."
The results, nevertheless, "remind us that antibiotics should not be given unless they are really needed, and we cannot exclude the possibility that unnecessary use of antibiotics may be exposing people to an increased risk of cancer," he concluded.
Similar comments were made by Thomas Seufferlein, MD, Department of Internal Medicine, Ulm University, Germany, who discussed the findings.
He agreed with the authors "that careful use of antibiotics is sensible and paramount," but added that more studies are needed on this suggestion of a link between antibiotic use and the observed increase in early CRC.
Previous studies have demonstrated that, in older adults, significant alterations in the structure and diversity of the gut microbiome induced by antibiotic therapy influence the development of colorectal cancer.
However, Perrott said that the impact of antibiotic use on early onset colorectal cancer has not been investigated.
The researchers therefore conducted a nested case–control study of primary care records to identify colorectal cancer cases diagnosed in Scotland between 1999 and 2011.
Patients were divided into those diagnosed before 50 years of age and those diagnosed at 50 years and older, and matched with up to five healthy controls.
The study included 7903 CRC cases, of which 5281 were colon cancer and 2622 rectal cancer, alongside 30,418 controls.
Among the CRC patients, 445 (5.6%) were under 50 years of age at diagnosis.
The team also analyzed antibiotic use history. Prescriptions for oral antibiotics, stratified by drug class and by anaerobic/nonanaerobic effect, were extracted and the total antibiotic exposure period was calculated and categorized as 0, 1-15, 16-60, and > 60 days.
Overall, 45% of the patients were prescribed antibiotics. Any antibiotic use was associated with a significantly increased risk of colon cancer, but this was most pronounced in patients aged less than 50 years at diagnosis.
Specifically, any antibiotic use was associated with an adjusted odds ratio of colon cancer of 1.49 (P = .018) in patients aged less than 50 years versus 1.09 (P = .029) in those aged 50 years and over.
In younger patients, the largest association between antibiotic use and colon cancer was seen in patients with a total antibiotic exposure of 1-15 days (at an adjusted odds ratio of 1.55), falling to 1.46 with 16-60 days of exposure, and no association for > 60 days exposure.
No such relationship was seen in patients with colon cancer aged 50 years and over at diagnosis.
There was also no significant relationship between any antibiotic use and the occurrence of rectal cancer, at an adjusted odds ratio of 1.17 (P = .493) in those aged under 50 years at diagnosis and 1.07 (P = .698) in older patients.
The study was supported by Cancer Research UK. Seufferlien has reported relationships with Amgen, Bayer, Merck, Sanofi, Celgene, Shire, Roche, Falk Foundation, AstraZeneca, Lilly, Merck-Serono, Servier, Pierre Fabre, Cantargia, and Boehringer Ingelheim.
WCGC 2021. Presented July 2, 2021. Abstract SO-25.
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