Do weak opioids increase risk of GI cancers?

Evidence on the association of weak opioids with a higher risk of oesophageal and colorectal cancer is not reliable, but there appears to be a small association with gastric cancer, suggests a study.

“We observed no consistent evidence of an association between weak opioids and an increased risk of oesophageal and colorectal cancer, but some evidence of a small association between weak opioids and gastric cancer,” the researchers said.

Scottish general practice records from the Primary Care Clinical Informatics Unit Research database were used to carry out this series of nested case-control studies. The researchers identified a total of 2,432 oesophageal, 1,443 gastric, and 8,750 colorectal cancer cases, diagnosed between 1999 and 2011, and matched these with up to five controls.

Use of weak opioids was ascertained from prescribing records. Using conditional logistic regression, the researchers calculated odds ratios (ORs) and 95 percent confidence intervals (CIs), adjusting for relevant comorbidities and medication use.

No significant association was observed between weak opioids and colorectal cancer (adjusted OR, 0.96, 95 percent CI, 0.90‒1.02; p=0.15), but an increased risk of oesophageal (adjusted OR, 1.16, 95 percent CI, 1.04‒1.29; p=0.01) and gastric cancer (adjusted OR, 1.26, 95 percent CI, 1.10‒1.45; p=0.001) was noted. [Br J Clin Pharmacol 2023;89:2757-2766]

When weak opioid users were compared with those of another analgesic, the association with oesophageal cancer (adjusted OR, 1.03, 95 percent CI, 0.86‒1.22; p=0.76) was attenuated, but not with gastric cancer (adjusted OR, 1.29, 95 percent CI, 1.02‒1.64; p=0.04).

“The cause of the association between weak opioids and gastric cancer is unknown,” the researchers said. “It could reflect our hypothesis that a decrease in gastrointestinal (GI) motility increases risk of GI tract cancers.”

In experimental models, opioids influence the integrity of GI epithelial cells and increase pro-inflammatory cytokines through induction of the immune system. [J Surg Res 2017;219:214-221; Anesth Analg 1998;86:166-172]

“Alternatively, the gastric cancer association could reflect confounding by indication, and there was some evidence of this as the association between paracetamol, used for pain, and gastric cancer was similar to the association for weak opioids,” the researchers said.

“Future studies of weak opioids and gastric cancer are warranted and should attempt to account for chronic pain,” they added.

On the other hand, the lack of association between weak opioids and oesophageal and colorectal cancer is an encouraging finding for both patients and physicians, according to the researchers.

Weak opioids are helpful in providing pain relief for mild to moderate pain in both acute and chronic settings. These are also included in the model list of essential medicines by the World Health Organization. [https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2021.02]

“Opioids remain useful analgesics; further studies are required to replicate these findings, both for opioids and other medications which affect GI motility, to help inform clinicians' safe prescribing practice,” the researchers said.