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\begin{document}

\title{Exposure to weak opioids and risk of gastrointestinal tract cancers: A
series of nested case-control studies.}



\author[1]{Martin Houston}%
\author[1]{Una McMenamin}%
\author[2]{Brian Johnston}%
\author[1]{Ronald McDowell}%
\author[3]{Carmel Hughes}%
\author[4]{Peter Murchie}%
\author[1]{C Cardwell}%
\affil[1]{Queen's University Belfast Centre for Public Health}%
\affil[2]{Royal Victoria Hospital}%
\affil[3]{Queen's University of Belfast School of Pharmacy}%
\affil[4]{University of Aberdeen Institute of Applied Health Sciences}%


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  \date{June 17, 2024}


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\begin{abstract}
Background There is evidence gastrointestinal (GI) motility may play a
role in the development of GI cancers. Weak opioids (codeine and
dihydrocodeine) decrease GI motility, but their effect on GI cancer risk
has not been assessed. Aim To assess the association between weak
opioids and cancers of the GI tract. Methods A series of nested
case-control studies was conducted using Scottish general practice
records from the Primary Care Clinical Informatics Unit Research
database. Oesophageal (n=2,432), gastric (n=1,443), and colorectal
cancer (n=8,750) cases, diagnosed between 1999 and 2011, were identified
and matched with up to five controls. Weak opioid use was identified
from prescribing records. Odds ratios (OR) and 95\% confidence intervals
(CI) were calculated using conditional logistic regression, adjusting
for relevant comorbidities and medication use. Results There was no
association between weak opioids and colorectal cancer (adjusted
OR=0.96, CI 0.90, 1.02, p=0.15). There was an increased risk of
oesophageal (adjusted OR=1.16, CI 1.04, 1.29, p=0.01) and gastric cancer
(adjusted OR=1.26, CI 1.10, 1.45, p=0.001). The associations for
oesophageal cancer, but not gastric cancer, were attenuated when weak
opioid users were compared with users of another analgesic (adjusted
OR=1.03 CI 0.86, 1.22, p=0.76 and adjusted OR=1.29 CI 1.02, 1.64, p=0.04
respectively). Conclusion In this large population-based study, there
was no consistent evidence of an association between weak opioids and
oesophageal or colorectal cancer risk, but a small increased risk of
gastric cancer. Further investigation is required to determine whether
this association is causal or reflects residual confounding or
confounding by indication.%
\end{abstract}%



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