Background: Antibiotics have recently been suggested to increase the risk of colorectal cancer. Here, we aimed to investigate the association of frequent antibiotic use and genetic susceptibility with the increased risk of the development of colorectal cancer. Therefore, a genome-wide association study was conducted in colorectal cancer patients with frequent antibiotic use and controls to identify potential chromosomal regions that could indicate an increased risk of colorectal cancer associated with antibiotic use. The results were replicated with a case-case analysis. Methods: A genome-wide case-control study involving 143 colorectal cancer cases with frequent exposure to antibiotics and 1642 healthy individuals with unknown antibiotic use was undertaken. A logistic regression model was used to identify associations between certain chromosomal regions (loci) and the risk of colorectal cancer in cases with frequent antibiotic use. The results were replicated in a follow-up association case-case study comparing the frequent users to those with a more modest use of antibiotics. Results: Six chromosomal regions were associated with colorectal cancer in patients exposed to frequent antibiotic use. Two of the six regions contained genes already suggested to be associated with colorectal cancer tumorigenesis, epithelial-mesenchymal transition and colorectal cancer recurrence. The results for the six chromosomal regions were further replicated in a case-case analysis where all the chromosomal regions were confirmed with high odds ratios (ORs) supporting the hypothesis that frequent antibiotic use is associated with an increased risk of colorectal cancer development. Conclusions: The study suggested that genetic modifiers could influence the risk of colorectal cancer associated with the frequent use of antibiotics.
背景：近期有研究表明抗生素可能增加结直肠癌的发病风险。本研究旨在探讨频繁使用抗生素与遗传易感性对结直肠癌风险增加的联合影响。为此，我们对频繁使用抗生素的结直肠癌患者及对照组进行了全基因组关联分析，以识别可能与抗生素使用相关的结直肠癌风险增加的潜在染色体区域，并通过病例-病例分析对结果进行验证。 方法：本研究开展了一项全基因组病例对照研究，纳入143例频繁暴露于抗生素的结直肠癌患者及1642例抗生素使用情况未知的健康个体。采用逻辑回归模型分析特定染色体区域（基因座）与频繁使用抗生素的结直肠癌患者发病风险之间的关联。随后在随访关联研究中，通过病例-病例分析比较频繁使用抗生素患者与抗生素使用较少患者，对上述结果进行验证。 结果：在频繁使用抗生素的患者中，发现六个染色体区域与结直肠癌发病相关。其中两个区域包含已被证实与结直肠癌发生、上皮-间质转化及结直肠癌复发相关的基因。通过病例-病例分析对这六个染色体区域进行验证，所有区域均显示出较高的比值比（OR），进一步支持频繁使用抗生素与结直肠癌风险增加相关的假设。 结论：本研究表明遗传修饰因子可能影响频繁使用抗生素相关的结直肠癌发病风险。
A GWAS Suggesting Genetic Modifiers to Increase the Risk of Colorectal Cancer from Antibiotic Use
肿瘤(癌症)患者之家