Antibiotic use and cancer risk: Repeat exposure poses harm

Issue: June 25, 2016

For years, data have suggested that previous exposure to antibiotics may be associated with an increased risk for diabetes, as well as an increased risk for obesity among certain populations.

Research now suggests that years of repeat exposure to various antibiotics is associated with an increased risk for specific cancer types.

A nested, case-control, observational study in which investigators used a large population-based primary care database to assess 15 common malignancies showed that recurrent exposure to certain antibiotics increased the risk for specific cancers, possibly through changes in composition and diversity of the microbiota.

“Because this is only an observational study, our results do not support cause and effect, but they do support an association between repeated antibiotic exposure and cancer risk,” researcher Ben Boursi, MD, postdoctoral researcher at University of Pennsylvania’s Perelman School of Medicine, said in an interview.

HemOnc Today spoke with Boursi about the potential for antibiotics to increase the risk for different cancer types and the importance of physicians prescribing antibiotics only when truly indicated.

Question: What do we know about the association between the microbiota and cancer risk?

Answer: We know from previous studies in animal models that mice that were raised in a germ-free environment and were exposed to carcinogens developed significantly fewer colonic polyps and tumors compared with conventional mice. In another animal model, researchers were able to transmit the cancer phenotype from diseased to healthy mice using fecal samples. In humans, changes in the microbiota composition were described in malignant and pre-malignant lesions in the gastrointestinal tract. It has been suggested that the microbiota composition might affect cancer risk through induction of chronic inflammation, changes in the normal tissue metabolism, direct genotoxic effects and weakening of the immune response.

Q: You led a study published in European Journal of Cancer about recurrent antibiotic exposure promoting cancer formation. Can you discuss the motivation for this study, as well as the key findings?

A: Our study examined the association between antibiotic exposure and the risk for 15 common cancers. We evaluated different antibiotics that were prescribed more than 1 year before cancer diagnosis. We found a positive association between cancer risk and repeated exposure to specific antibiotics. Although there was almost no change in risk with a single course of antibiotics, the risk increased with increasing number of antibiotic courses prescribed. We observed no association between exposure to antivirals or antifungals and cancer risk. There also was no association between antibiotic prescriptions and melanoma or carcinoma of the cervix that are known to be caused by UV exposure and HPV infection.

Q: How might the findings change the way the physician practices in terms of prescribing antibiotics? Should the course of antibiotics be re-examined?

A: Physicians and patients should be aware of both the short- and long-term risks of antibiotics. There is a need to decrease unnecessary antibiotic prescriptions, especially among patients who present in the clinic with nonspecific symptoms. Regarding the duration of antibiotic treatment, even 1 day of treatment may alter the microbiota composition. Therefore, it is important for clinicians to prescribe antibiotics only when indicated.

Q: Is one specific population — eg, men vs. women, younger vs. older — more susceptible to cancer risk from antibiotic exposure?

A: Specifically in our study, there were no differences in cancer risk with antibiotic use by sex. However, it is important to note that we included only adults who were diagnosed with cancer after the age of 20 years and, therefore, cannot generalize our results to younger adults. Future studies should focus on the impact of antibiotic use on various outcomes among the very young, including cancer risk.

Q: Is one type of antibiotic associated with a higher risk for cancer?

A: In our study, the magnitude of risk varied by antibiotic and tumor type. Globally, penicillins were associated with the most significant cancer risk, mainly in the gastrointestinal and genitourinary systems, as well as the lungs. Tetracyclines, on the other hand, were associated only with modest increase in prostate cancer risk.

Q: What would you say to patients who know about the associated risk for cancer from antibiotic use and do not want to take their prescribed antibiotic?

A: Irresponsible use of antibiotics can cause antibiotic resistance at the population level, and growing data suggest that antibiotics may even increase the risk for diabetes, obesity and maybe certain cancers. It is important to mention, however, that antibiotics for the right indications save lives and prevent significant morbidities. So, as always, we should talk with our treating physician about the need for antibiotics for a given condition and better understand the possible risks and benefits of the antibiotic prescribed.

Q: What would you like to see from future research into antibiotic exposure and cancer risk?

A: Future studies should focus on evaluating specific pathologic pathways behind this association. For example, how do the microbiota affect our genes and immune system? Because microbiota is more prone to changes during the first years of life, additional investigations should evaluate the impact of antibiotic exposure specifically during childhood. However, it is important to note that these studies will require decades of follow-up. – by Jennifer Southall

Reference:

Boursi B, et al. Eur J Cancer. 2015;doi:10.1016/j.ejca.2015.08.015.

For more information:

Ben Boursi, MD, can be reached at University of Pennsylvania, 34th and Spruce streets, Philadelphia, PA 19104; email: boursi@mail.med.upenn.edu.

Disclosure: Boursi reports no relevant financial disclosures.