Recurrent antibiotic exposure may promote cancer formation--Another step in understanding the role of the human microbiota?
Recurrent antibiotic exposure may promote cancer formation--Another step in understanding the role of the human microbiota?
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DOI：
10.1016/j.ejca.2015.08.015
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Yang YX
中科院分区：
文献类型：
--
作者：
Boursi B;Mamtani R;Haynes K;Yang YX
细菌生态失调以前在人类恶性肿瘤中有描述。在最近的动物模型中，肿瘤易感性通过粪便移植传播。我们的目的是进一步评估抗生素暴露与癌症风险之间的可能联系。我们使用一个大型的基于人群的电子病历数据库对15种常见恶性肿瘤进行了巢式病例对照研究。病例定义为具有特定恶性肿瘤的任何医学代码的病例。排除了家族性癌症综合征的个体。对于每一个案例，四个合格的控制匹配的年龄，性别，实践网站，并在索引日期之前的随访时间，使用发病率密度抽样。关注的暴露是索引日期前>1年的抗生素治疗。使用条件Logistic回归估计每种抗生素类型的校正比值比（AOR）和95%CI。分析了125，441例病例和490，510例匹配对照。对于胃肠道恶性肿瘤，青霉素的使用与食管癌、胃癌和胰腺癌的风险升高相关。随着抗生素疗程数的增加，相关性增加，对于与青霉素>5个疗程相关的胃癌，相关性达到1.4（95%CI 1.2-1.8）。使用青霉素、头孢菌素或大环内酯类药物增加肺癌风险（>5个疗程青霉素的AOR：1.4 95%CI 1.3-1.6）。使用青霉素、喹诺酮类、磺胺类和四环素类药物，前列腺癌的风险适度增加。乳腺癌的风险与磺胺类药物的暴露适度相关。抗病毒药物和抗真菌药物的使用与癌症风险之间没有关联。反复暴露于某些抗生素可能与特定器官部位的癌症风险有关。
Bacterial dysbiosis was previously described in human malignancies. In a recent animal model, tumor susceptibility was transmitted using fecal transplantation. Our aim was to further evaluate possible association between antibiotic exposure and cancer risk. We conducted nested case-control studies for 15 common malignancies using a large population-based electronic medical records 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%CIs were estimated for each antibiotic type using conditional logistic regression. 125,441 cases and 490,510 matched controls were analyzed. For gastro-intestinal malignancies, the use of penicillin was associated with an elevated risk of esophageal, 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, cephalosporines, 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 for breast cancer was modestly associated with exposure to sulphonamides. There was no association between use of anti-virals and anti-fungals and cancer risk. Recurrent exposure to certain antibiotics may be associated with cancer risk in specific organ sites.