Use of Antibiotics and Risk of Cancer: A Systematic Review and Meta-Analysis of Observational Studies

Abstract

The association between antibiotic use and risk of cancer development is unclear, and clinical trials are lacking. We performed a systematic review and meta-analysis of observational studies to assess the association between antibiotic use and risk of cancer. PubMed, the Cochrane Library and EMBASE were searched from inception to 24 February 2019 for studies reporting antibiotic use and subsequent risk of cancer. We included observational studies of adult subjects with previous exposure to antibiotics and available information on incident cancer diagnoses. For each of the eligible studies, data were collected by three reviewers. Risk of cancer was pooled to provide an adjusted odds ratio (OR) with a 95% confidence interval (CI). The primary outcome was the risk of developing cancer in ever versus non-antibiotic users. Cancer risk’s association with antibiotic intake was evaluated among 7,947,270 participants (n = 25 studies). Overall, antibiotic use was an independent risk factor for cancer occurrence (OR 1.18, 95%CI 1.12–1.24, p < 0.001). The risk was especially increased for lung cancer (OR 1.29, 95%CI 1.03–1.61, p = 0.02), lymphomas (OR 1.31, 95%CI 1.13–1.51, p < 0.001), pancreatic cancer (OR 1.28, 95%CI 1.04–1.57, p = 0.019), renal cell carcinoma (OR 1.28, 95%CI 1.1–1.5, p = 0.001), and multiple myeloma (OR 1.36, 95%CI 1.18–1.56, p < 0.001). There is moderate evidence that excessive or prolonged use of antibiotics during a person’s life is associated with slight increased risk of various cancers. The message is potentially important for public health policies because minimizing improper antibiotic use within a program of antibiotic stewardship could also reduce cancer incidence.

Antibiotics, cancer risk and oncologic treatment efficacy: a practical review of the literature

“…Relevant publications have raised the hypothesis that certain drugs are associated with carcinogenesis [ 32 , 33 ] and that the regular use of antibacterial drugs may be associated with cancer development [ 34 ]. According to a recent meta-analysis of 25 observational case–control or cohort studies, there is moderate evidence that the prolonged or excessive use of antibiotics during a person’s life is associated with a slight increased risk of various types of cancers [ 35 ]. Besides, a nested case–control study for 15 common malignancies revealed that a recurrent exposure to certain antibiotics frequently used in the community may be associated with cancer risk in specific organ sites [ 35 , 36 ].…”

“…According to a recent meta-analysis of 25 observational case–control or cohort studies, there is moderate evidence that the prolonged or excessive use of antibiotics during a person’s life is associated with a slight increased risk of various types of cancers [ 35 ]. Besides, a nested case–control study for 15 common malignancies revealed that a recurrent exposure to certain antibiotics frequently used in the community may be associated with cancer risk in specific organ sites [ 35 , 36 ]. Since antibiotics have no known direct carcinogenic effect, the main hypothesis for the increased cancer risk focuses on their influence on the composition of the human microbiome, which involves the bacteria that compose the microbiota, their genes, metabolites and interactions with one another, as well as with their host collectively, including the immune system [ 4 , 37 ].…”

“…On the primary analysis of overall cancer incidence, the previous exposure to antibiotics increased the risk of cancer by 18% (odds ratio (OR): 1.18, p < 0.001), which was particularly increased for the following primary tumours: lung cancer (OR 1.29, p = 0.02), renal cell carcinoma (OR 1.28, p = 0.001), pancreatic cancer (OR 1.28, p = 0.019), lymphomas (OR 1.31, p < 0.001) and multiple myeloma (OR 1.36, 95% CI 1.18–1.56, p < 0.001). Higher risks were found in individuals with either a long duration of antibiotic exposure or higher doses [ 35 ]. In addition, the antibiotic classes with the strongest significant association with cancer development were beta-lactams, macrolides and quinolones [ 35 ].…”

“…Higher risks were found in individuals with either a long duration of antibiotic exposure or higher doses [ 35 ]. In addition, the antibiotic classes with the strongest significant association with cancer development were beta-lactams, macrolides and quinolones [ 35 ].…”

“…Furthermore, several bacteria species have been shown to be enriched in lung cancer patients compared with healthy individuals [ 38 ]. Modifications in lung microbiota induced by antibiotics might explain the higher incidence of lung cancer amongst the users of antibiotics in the aforementioned meta-analysis [ 35 ].…”