Recurrent antibiotic exposure may promote cancer formation--Another step in understanding the role of the human microbiota?

BACKGROUND Bacterial dysbiosis was previously described in human malignancies. In a recent animal model, tumour susceptibility was transmitted using faecal transplantation. Our aim was to evaluate possible association between antibiotic exposure and cancer risk. METHODS We conducted nested case-control studies for 15 common malignancies using a large population-based electronic medical record database. Cases were defined as those with any medical code for the specific malignancy. Individuals with familial cancer syndromes were excluded. For every case, four eligible controls matched on age, sex, practice site and duration of follow-up before index-date were selected using incidence-density sampling. Exposure of interest was antibiotic therapy >1 year before index-date. Adjusted odds-ratios (AORs) and 95% confidence intervals (CIs) were estimated for each antibiotic type using conditional logistic regression. RESULTS 125,441 cases and 490,510 matched controls were analysed. For gastro-intestinal malignancies, the use of penicillin was associated with an elevated risk of oesophageal, gastric and pancreatic cancers. The association increased with the number of antibiotic courses and reached 1.4 for gastric cancers associated with >5 courses of penicillin (95% CI 1.2-1.8). Lung cancer risk increased with the use of penicillin, cephalosporins, or macrolides (AOR for >5 courses of penicillin: 1.4 95% CI 1.3-1.6). The risk of prostate cancer increased modestly with the use of penicillin, quinolones, sulphonamides and tetracyclines. The risk of breast cancer was modestly associated with exposure to sulphonamides. There was no association between the use of anti-virals and anti-fungals and cancer risk. CONCLUSION Recurrent exposure to certain antibiotics may be associated with cancer risk in specific organ sites.

[1]  Shawn W. Polson,et al.  High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity , 2014, Nature.

[2]  A. Feinstein,et al.  The problem of "protopathic bias" in case-control studies. , 1980, The American journal of medicine.

[3]  J H Lubin,et al.  Biased selection of controls for case-control analyses of cohort studies. , 1984, Biometrics.

[4]  M. Cheng,et al.  Microbiota modulate tumoral immune surveillance in lung through a γδT17 immune cell-dependent mechanism. , 2014, Cancer research.

[5]  Kevin Haynes,et al.  Cancer incidence in The Health Improvement Network , 2009, Pharmacoepidemiology and drug safety.

[6]  W. Bilker,et al.  Validation studies of the health improvement network (THIN) database for pharmacoepidemiology research , 2007, Pharmacoepidemiology and drug safety.

[7]  G. Hajishengallis,et al.  The keystone-pathogen hypothesis , 2012, Nature Reviews Microbiology.

[8]  E. Giovannucci,et al.  Acne and risk of prostate cancer , 2007, International journal of cancer.

[9]  Les Dethlefsen,et al.  The Pervasive Effects of an Antibiotic on the Human Gut Microbiota, as Revealed by Deep 16S rRNA Sequencing , 2008, PLoS biology.

[10]  T. Keku,et al.  Gut Microbiome and Colorectal Adenomas , 2014, Cancer journal.

[11]  W. Bilker,et al.  The relationship between time since registration and measured incidence rates in the General Practice Research Database , 2005, Pharmacoepidemiology and drug safety.

[12]  P. Hartge,et al.  Urinary tract infection and risk of bladder cancer. , 1984, American journal of epidemiology.

[13]  Anders F. Andersson,et al.  Short-term antibiotic treatment has differing long-term impacts on the human throat 1 and gut microbiome 2 “ Running title " : Long-term antibiotic impacts 3 4 , 2010 .

[14]  A. Hajeer,et al.  Association between antibiotic use and risk of prostate cancer , 2010, International journal of cancer.

[15]  A. Maguire,et al.  The importance of defining periods of complete mortality reporting for research using automated data from primary care , 2009, Pharmacoepidemiology and drug safety.

[16]  J. Tap,et al.  Microbial Dysbiosis in Colorectal Cancer (CRC) Patients , 2011, PloS one.

[17]  D. Chia,et al.  Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer , 2011, Gut.

[18]  A. Aromaa,et al.  Antibiotic use predicts an increased risk of cancer , 2008, International journal of cancer.

[19]  C. Hoebe,et al.  Trends in Antibiotic Prescribing in Adults in Dutch General Practice , 2012, PloS one.

[20]  J. Shamonki,et al.  Microbial Dysbiosis Is Associated with Human Breast Cancer , 2014, PloS one.

[21]  Sang-Uk Seo,et al.  Role of the gut microbiota in immunity and inflammatory disease , 2013, Nature Reviews Immunology.

[22]  S. Hernández-Díaz,et al.  Antibiotic Use and the Risk of Lung Cancer , 2008, Cancer Epidemiology Biomarkers & Prevention.

[23]  E. Cario Microbiota and innate immunity in intestinal inflammation and neoplasia , 2013, Current opinion in gastroenterology.

[24]  D. Pezet,et al.  High Prevalence of Mucosa-Associated E. coli Producing Cyclomodulin and Genotoxin in Colon Cancer , 2013, PloS one.

[25]  L. G. García Rodríguez,et al.  Reduced Risk of Colorectal Cancer among Long-Term Users of Aspirin and Nonaspirin Nonsteroidal Antiinflammatory Drugs , 2001, Epidemiology.

[26]  Amy M. Sheflin,et al.  Stool Microbiome and Metabolome Differences between Colorectal Cancer Patients and Healthy Adults , 2013, PloS one.

[27]  A. Bourke,et al.  Generalisability of The Health Improvement Network (THIN) database: demographics, chronic disease prevalence and mortality rates. , 2011, Informatics in primary care.

[28]  R. Peek,et al.  Gastrointestinal malignancy and the microbiome. , 2014, Gastroenterology.