- Colon cancer rates are increasing among younger people in the United States.
- Scientists think that antibiotics could upset the balance of the gut microbiome, leading to immune system dysregulation and causing disease.
- New research has found a link between oral antibiotic use and the risk of developing colon cancer.
- These results could help increase awareness of the potential harms associated with unnecessary antibiotic use.
Colorectal cancer (CRC) is currently the second most common cause of cancer-related deaths in the U.S.
Traditionally, CRC develops in older people. However, the incidence of CRC in younger people — meaning those below 50 years of age — has increased over the last 25 years.
Researchers from the United Kingdom recently conducted a large population-based case-controlled study involving data from almost 40,000 people.
They identified a link between antibiotic use and the risk of developing colon cancer before 50 years of age. This link was stronger in younger people. Their findings appear in the British Journal of Cancer.
Lead author Dr. Leslie Samuel, who is based at the University of Aberdeen, explained the situation to Medical News Today:
“There has been a substantial increase in antibiotics consumption by children across the globe, and it is likely that this is a factor — perhaps a minor factor — in the increased, and unfortunately increasing, incidence of both colon and rectal cancer in young people.”
“Other factors that are also likely related include refined food diets high in sugar, obesity, physical inactivity, and diabetes,” he continued.
Antibiotics and the microbiome
The collective name for the microorganisms living in the gastrointestinal tract is the gut microbiome, and it has a complex relationship with our health.
These microorganisms help digest food, break down toxic chemicals, and release important substances that help regulate the immune system. Scientists believe that many diseases are linked to a shift away from the healthy balance of these organisms.
Antibiotics can upset the balance of the gut microbiome, which can lead to the over- or underproduction of certain chemicals that experts believe to be important for regulating the immune system. This imbalance may even contribute to the development of some cancers.
Previous studies have found a possible link between antibiotic use and CRC. However, these studies have focused mainly on older adults, and the results are not conclusive.
Gathering the data
Recently, a group of researchers set out to identify whether antibiotic use was associated with the development of CRC in younger people. The U.K.-based scientists work at the University of Aberdeen, National Health Service (NHS) Grampian, and Queen’s University Belfast.
The scientists also wanted to understand whether the risk varies among different types of CRC or antibiotics.
Using routine 1999–2011 data from across Scotland, they found 7,903 people with a CRC diagnosis and matched them to 30,418 people who did not have a cancer diagnosis.
The researchers matched the participants based on location, approximate year of birth, sex, and approximate year of database registration.
They removed from the analysis anyone who was taking immunosuppressing drugs or living with a health condition predisposing them to CRC.
The scientists split the data into two groups: early onset and late onset. Those in the first group received their diagnosis before reaching 50 years of age, whereas those in the late onset group were 50 years old or older at the time of diagnosis. There were 445 people in the early onset group and 7,458 in the late onset group.
As evidence suggests that risk factors may differ between early onset and late onset disease, the team analyzed these groups separately.
The database included prescriptions for oral antibiotics, which the researchers classified by drug class and the presence or absence of anti-anaerobic effects. They did this to provide insight into the types of bacteria that might be associated with CRC.
Anti-anaerobic drugs kill anaerobic bacteria — those that do not need oxygen to live. These bacteria make up the vast majority of the human gut microbiome.
The team also collected other important information, including:
- existing health conditions, known as comorbidities
- use of other drugs, such as aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs)
- smoking status
- alcohol use
Where data were available, the scientists carried out separate analyses that included the exact location of the primary tumor and body mass index (BMI).
About 55% of those with CRC in each group were male, and almost 50% of participants had received a prescription for antibiotics. More people who developed CRC had taken antibiotics compared with those who did not develop CRC.
Overall, antibiotic use was associated with an estimated 49% higher risk of colon cancer in those younger than 50 years and an estimated 9% higher risk in those aged 50 years and over.
Dr. Samuel told MNT:
“It was not surprising to find a link between antibiotics and an increased risk of colon cancer in younger people, but it is true that the magnitude of the risk (nearly 50%) was a surprise.”
Antibiotic use was not significantly associated with an increased risk of rectal cancer in either of the age groups. Also, the risk did not seem to be linked to the duration of the antibiotics course.
Anti-anaerobic antibiotics had an association — although not a statistically significant one — with an increased risk of colon cancer in both age groups. Non-anti-anaerobic antibiotics did have a statistically significant difference in CRC risk in the younger age group but not in the older age group.
When the researchers adjusted the data for BMI, medication use, and comorbidities, the association between CRC risk and antibiotics increased. However, the authors note that the sample size in this analysis was not large enough to make any solid claims.
Thoughts on the findings
The researchers state that multiple factors are likely driving the increase in early onset CRC, and it remains uncertain whether this link is causal. These factors include dietary aspects, obesity, stress, and reduced exercise.
Alice Davies, health information manager at Cancer Research UK, says: “Currently, there isn’t enough evidence to say if antibiotics are definitely increasing people’s risk, but this gives us another piece of the puzzle. Continued research is needed — we still need to understand which antibiotics might increase the risk, how this happens, and how much they increase risk by.”
“Antibiotics are an essential tool in combatting common illnesses, so it’s important to follow your doctor’s advice on taking them,” she explains.
The authors of the paper say it is likely that the antibiotic-associated changes in the microbiome disrupt the gut bacteria that usually stimulate the immune system. This disruption may encourage pathogenic, or disease-causing, bacteria to move in. This recolonization, the authors explain, is likely to be carcinogenic.
In other words, it is not the antibiotics that are carcinogenic, but the changes in gut flora that occur following their use.
Dr. Samuel told MNT that he would like to see further research into why particular areas of the colon are more at risk. “Given […] that the risks appear to be particularly higher for proximal (or right-sided) colon cancers,” he said, “it would be of interest to know the microbiome of the ‘normal’ proximal colon and how it changes in different situations, such as in people on refined high sugar diets, for example.”
“If we were able to know what the significant differences in the microbiome were between ‘normal’ and patients with risk factors, then we can design strategies to reduce the differences, [such as] dietary [changes], probiotics, [and] fecal transplants,” he explained.
The authors of the paper acknowledge that the group with early onset CRC was fairly small, especially as it was necessary to split the data between non-anti-anaerobic and anti-anaerobic antibiotics.
They add that it might be irrelevant whether antibiotics are anti-anaerobic because most antibiotics have dual anti-anaerobic and aerobic activity.
Also, the dataset did not contain information on the family history or dietary habits of the participants, and there was BMI information for only about one-third of the sample. Both of these factors may have a significant influence on CRC risk.
MNT asked Dr. Samuel whether he thought that the findings might inform policy changes, such as screening programs:
“Our results remind our policymakers of the steady increase in the incidence of colon and rectal cancer in younger people, as well as the risk factors that can be changed through changes in social policies.”
“These include promoting physical activity, reducing obesity, reducing the focus on energy dense, high sugar diets, reducing average alcohol consumption, and promoting professional and public awareness of the risks, as well as benefits from medicines such as antibiotics.”
Source: Read Full Article