Regular pharmaceutical opioid use was found to be associated with an elevated risk for cancers previously associated with opium consumption, but not for other cancers, according to findings from a large-scale study led by the International Agency for Research on Cancer (IARC) that was published in eClinicalMedicine.
“These findings suggest that regular use of pharmaceutical opioids may increase the risk of developing cancers previously linked to opium consumption, raising important concerns for public health,” the study authors noted in their report. “Given the widespread and increasing global use of opioids, particularly for chronic noncancer pain, even modest increases in cancer risk could have substantial population-level implications.”
The IARC also published a set of questions and answers regarding how these findings should be interpreted in clinical practice. “These findings should not be interpreted as grounds for immediate clinical application or changes to prescribing guidelines. Rather, they underscore the need for further research to determine whether the observed associations are causal, to quantify their magnitude, and to clarify their clinical relevance,” the agency noted.
Background and Study Methods
Pharmaceutical opioids derived from or synthesized to mimic opium could be associated with cancer risk. Opium has been classified by the IARC as "carcinogenic to humans."
The IARC conducted a large observational and genetic analysis study to determine the associations between pharmaceutical opioids and cancer risks.
The researchers analyzed observational patient data from 472,955 participants in the UK Biobank prospective cohort from between 2006 and 2022 as well as two-sample Mendelian randomization analyses of data from 14 genome-wide association studies. They explored associations with six opium-related cancers (lung, pancreatic, bladder, esophageal, oropharyngeal, and laryngeal) and seven non–opium-related cancers (prostate, breast, colon, endometrial, kidney, ovarian, and brain).
Key Study Findings
In the observational analysis, regular opioid use was associated with increased risk for the opium-related cancers in ever-smoking (adjusted hazard ratio [aHR] = 1.33; 95% confidence interval [CI] = 1.22–1.43) and never-smoking patients (aHR = 1.32; 95% CI = 1.10–1.59), but was not associated with non–opium-related cancers (aHR = 0.96; 95% CI = 0.91–1.02).
Cancer risk increased with the strength of the opioid as well as duration of action. For weaker opioids, the aHR was 1.30 (95% CI = 1.20–1.40) and was 1.86 (95% CI = 1.43–2.40) for stronger opioids (P < .0001). For short-acting opioids, the aHR was 1.32 (95% CI = 1.22–1.42) and was 1.65 (95% CI = 1.24–2.18) for longer-acting opioids (P < .0001).
Both analyses showed that there were increased risks for most opium-related cancers, but there was an inverse association found with prostate cancer (aHR = 0.83; 95% CI = 0.76–0.91; odds ratio [OR] = 0.99; 95% CI = 0.92–1.05), and there were null associations with non–opium-related cancers. For lung cancer, the aHR was 1.39 (95% CI = 1.27–1.53) and the OR was 1.17 (95% CI = 1.17–1.07–1.29); for pancreatic cancer, the aHR was 1.24 (95% CI = 1.01–1.52) and the OR was 1.34 (95% CI = 1.11–1.62); for bladder cancer, the aHR was 1.26 (95% CI = 1.02–1.56) and the OR was 1.15 (95% CI = 1.03–1.29); for esophageal cancer, the aHR was 1.18 (95% CI = 0.94–1.49) and the OR was 1.24 (95% CI = 1.01–1.52); and for laryngeal cancer, the aHR was 1.37 (95% CI = 0.85–2.20) and the OR was 1.29 (95% CI = 1.04–1.61).
Mahdi Sheikh, MD, PhD, Scientist, Genomic Epidemiology Branch, International Agency for Research on Cancer in Lyon, France, is the corresponding author for this report.
Disclosure: This study was funded by the U.S. National Institutes of Health and the French National Cancer Institute. For full disclosures of the study authors, visit thelancet.com.
