A recent study looking for a link between antibiotics and cancer risk uncovers a complex relationship. The researchers conclude that there is an association between antibiotic use and an increase in colon cancer risk, but a decrease in rectal cancer risk.

With the advent of antibiotic resistance, doctors are more conscious than ever before of limiting these drugs. However, the use of antibiotics continues to grow globally. From 2000–2010, consumption increased by 35% to 70 billion doses each year. That equates to 10 doses for each human on earth. These staggering figures are the fuel that drives researchers to understand the impact of antibiotics on human health better.

Over recent years, scientists have begun to appreciate the significant role that gut bacteria play in maintaining a healthy body. Likewise, because antibiotics kill gut bacteria, they have the potential to make a lasting impact on human health.

In short, if antibiotics kill off a colony of "good" bacteria, it leaves a niche for "bad," or pathogenic bacteria to colonize. These pathogenic bacteria include ones that can be carcinogenic.

Moving forward with the research base

Earlier research has found associations between antibiotics and cancer, but current evidence is limited, as the authors of the most recent study note. For instance, some of the previous studies recruited relatively few participants; others did not account for cancer risk factors, such as smoking and alcohol use; yet more relied on participants to self-report their antibiotic usage, which is open to errors and lacks the type and dosage of the drugs. With that in mind, the authors of a new study, now appearing in the journal Gut, set out their intent: "Our aim was to investigate the associations between antibiotic use and site-specific colorectal cancer risk in the world's largest primary care database."

To investigate, they took data from the Clinical Practice Research Datalink from 1989–2012. This database carries the anonymized medical records of 11.3 million people from 674 doctor's offices across the United Kingdom.

The records contain detailed information about the types of drugs doctors prescribed, the dosage, and how they instructed people to take them.

From this information, the researchers extracted the records of 19,726 people, aged 40–90 years, who developed colon cancer and 9,254 who developed rectal cancer. They also collected information about 137,077 people who did not develop bowel cancer who they matched by age and sex.

Dissecting antibiotics and cancer by types

When the scientists collated information about antibiotic use, they focused on pills and tablets, as science currently has limited understanding of the impact of intravenous antibiotics on gut bacteria.

They split antibiotics into categories by drug class, for instance, tetracyclines and penicillins. They also categorized antibiotics by the type of bacteria they impact, namely, aerobic or anaerobic. Aerobic bacteria need oxygen to survive, whereas anaerobic bacteria do not.

They also categorized the type of cancer by its position: rectum, proximal colon (the section furthest from the rectum), and distal colon (the last part of the colon before the rectum).

They followed participants for a median of 8.1 years, during which time some 70% had taken antibiotics. Overall, the research team measured a relationship between colon cancer risk and the use of any antibiotic. As the authors outline: "Participants who subsequently developed colon cancers were more likely to be exposed to antibiotics as compared with controls (71.3% vs 69.1%)."

When they looked at this interaction in more detail, they found that "the effect, size, and pattern of risk varied by anatomical location." The effect was strongest for cancer in the proximal colon. They also showed that antibiotics that target anaerobic bacteria rather than aerobic bacteria primarily drive the relationship.

A surprise finding for rectal cancer

Conversely, the authors found that there was an association between antibiotic use and a reduced risk of rectal cancer. This link was stronger for longer exposures to antibiotics. More precisely, they showed a link between taking antibiotics for more than 60 days and a 15% reduction in the risk of rectal cancer.

When they investigated individual classes of antibiotics, they found that penicillin was "strongly associated with increased colon cancer risk." However, tetracyclines showed a reduced risk of rectal cancer. The links between antibiotics and cancer risk appeared to be long lived, as the authors explain: "The association between antibiotic exposure and colon cancer was seen in participants with antibiotic exposure more than 10 years before [bowel] detection."

Strengths and limitations of the study

This latest piece of research has many strengths; for instance, it is the largest study of its type. Also, thanks to the quality of the data, the scientists could account for a range of additional variables in their analysis. However, the authors also note the limitations, for example, the significant gaps in the data regarding lifestyle factors. These include the inability to confirm that a person took antibiotics correctly. Also, the database did not collate information on dietary intake, levels of physical activity, and family history of bowel cancer, all of which can impact risk.

The scientists went to great lengths to account for many factors in their analysis but were unable to eliminate every possibility. The authors conclude that "whether antibiotic exposure is causal or contributory to colon cancer risk, our results highlight the importance of judicious antibiotic use by clinicians."

Because antibiotics are so widespread, and because antibiotic resistance is in the spotlight, potentially adverse effects are likely to face growing scrutiny over the coming years.