Colorectal cancer risk reduction following macrogol exposure: a cohort and nested case control study in the UK

PLoS One. 2013 Dec 20;8(12):e83203. doi: 10.1371/journal.pone.0083203. eCollection 2013.

Abstract

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 (CI950.74-1.03) and ORadj = 0.80 (CI950.65-1.00) 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 (CI950.50-0.92), ORadj = 0.60 (CI950.40-0.90) and ORadj = 0.30 (CI950.14-0.64) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / prevention & control*
  • Female
  • Humans
  • Laxatives / therapeutic use*
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Polyethylene Glycols / therapeutic use*
  • Risk Factors
  • Risk Reduction Behavior*
  • United Kingdom

Substances

  • Laxatives
  • Polyethylene Glycols

Grants and funding

This study was funded by Norgine Ltd. The study design, analysis and interpretation were carried out independent of the funding source and the authors had contractual freedom to publish. An employee of the funder (Dr Chris Hewson) did, however, contribute to the introduction section of the manuscript, which we have acknowledged. The funders had no role in study design, data collection and analysis and decision to publish.