Colorectal Cancer Risk Reduction following Macrogol Exposure: A Cohort and Nested Case Control Study in the UK
Colorectal Cancer Risk Reduction following Macrogol Exposure: A Cohort and Nested Case Control Study in the UK
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DOI：
10.1371/journal.pone.0083203
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发表时间：
2013-12-20
期刊：
影响因子：
3.7
通讯作者：
de Vries, Corinne S.
中科院分区：
文献类型：
--
作者：
Charlton, Rachel A.;Snowball, Julia M.;de Vries, Corinne S.
背景和目的：动物研究已经证明大醇泻药可以降低结直肠癌（CRC）的风险。本研究旨在探讨大醇处方与结直肠癌风险之间的关系。方法：使用来自英国全科医学研究数据库的数据，在一组泻药使用者中进行病例对照研究。每个病例确定了6个对照，为了考虑到CRC的前置时间，在索引日期向后追溯1至5年选择了额外的对照集。在每个回溯指数日期建立之前，暴露于宏醇和协变量状态。使用条件逻辑回归计算经潜在混杂因素调整的大剂量乙醇处方后发生结直肠癌的风险。结果：共发现4734例结直肠癌病例；2722、2195、1789、1481和1214在指数日期回溯1至5年前接受过泻药处方。当指数日期向后追溯1年和2年时，观察到与“大醇后其他泻药”处方相关的结直肠癌风险无显著降低，与非大醇泻药暴露相比，ORadj = 0.87 （CI(95)0.74-1.03）和ORadj = 0.80 （CI(95)0.65-1.00）。ORadj = 0.68 (CI(95)0.50-0.92), ORadj = 0.60 （CI(95)0.40-0.90）和ORadj = 0.30 （CI(95)0.14-0.64）时，比值比进一步降低并具有显著性。然而，在“只服用大醇”和“服用大醇先于其他泻药”的类别中，没有观察到这种风险的降低。结论：在这项研究中，我们观察到在考虑到结直肠癌的前置时间后，大醇处方降低了结直肠癌的风险。需要进一步的研究来确定这种联系是否存在因果关系，以及是否可以部分地通过选择性处方来解释。
Background and Aims:Animal studies have demonstrated macrogol laxatives may reduce colorectal cancer (CRC) risk. This study aimed to investigate the association between macrogol prescribing and CRC risk.Methods: A case-control study nested within a cohort of laxative users was conducted using data from the UK General Practice Research Database. Six controls per case were identified and to account for the lead time of CRC, additional control sets were selected on the index date backdated by 1 to 5 years. Exposure to macrogols and covariate status before each of the backdated index dates was established. Conditional logistic regression was used to calculate the risk of CRC following macrogol prescribing adjusted for potential confounders.Results: 4734 incident CRC cases were identified; 2722, 2195, 1789, 1481 and 1214 had received a laxative prescription before the index dates backdated by 1 to 5 years. A suggestion of a non-significant reduction in CRC risk associated with 'macrogol after other laxative' prescribing was observed when the index date was backdated by 1 and 2 years, ORadj = 0.87 (CI(95)0.74-1.03) and ORadj = 0.80 (CI(95)0.65-1.00) compared to non-macrogol laxative exposure. The odds ratios reduced further and were significant when backdated by 3, 4 and 5 years, ORadj = 0.68 (CI(95)0.50-0.92), ORadj = 0.60 (CI(95)0.40-0.90) and ORadj = 0.30 (CI(95)0.14-0.64) respectively. This reduction in risk was not observed, however, for 'macrogol only' and 'macrogol before other laxative' exposure categories.Conclusions: In this study we observed a reduced CRC risk associated with macrogol prescribing after accounting for the lead time for CRC. Further studies are required to determine whether the association is causal and whether it can partly be explained by selective prescribing.