Opium and opioid use and cancer risk: A systematic review and meta-analysis of epidemiological studies

Opium use has been suggested as a possible risk factor for several cancers. While increased risk may be attributable to adulterants or smoking by-products, direct effects for opium alkaloids remains a possibility. Considering the overlap between natural and semi-synthetic or synthetic opioids, such an effect may entail increased risk in a broader population. We reviewed reports on associations between opium or opioid use and cancer. MEDLINE, Scopus, and Web of Science were searched. Epidemiological studies were included. Two researchers performed screening, data extraction, and quality assessment independently. Meta-analysis was carried out using a random-effects model. 82 publication (from 78 studies) contributed to the meta-analysis. Opium use was associated with increased cancer odds (OR = 3.55; 95% CI 2.94, 4.29; 95% PI 1.07, 11.82), particularly for bladder, laryngeal, and oesophageal cancers. In contrast, opioids use showed a modest association in case-control studies (OR 1.04; 95% CI 1.00, 1.07, 95% PI 0.94, 1.15), and a non-significant trend in cohort studies (HR = 1.44; 95% CI 0.98, 2.11; 95% PI 0.25, 8.32). Opioid use was also associated with increased cancer mortality (HR = 1.69; 95% CI 1.16, 2.46; 95% PI 0.36, 7.98). However, high heterogeneity, residual confounding, and the paucity of longitudinal evidence preclude causal inferences.