Akrami Rahim, Hadji Maryam, Rashidian Hamideh, Nazemipour Maryam, Naghibzadeh-Tahami Ahmad, Ansari-Moghaddam Alireza, Zendehdel Kazem, Mansournia Mohammad Ali
Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio 70150, Finland.
Glob Epidemiol. 2024 Dec 30;9:100182. doi: 10.1016/j.gloepi.2024.100182. eCollection 2025 Jun.
Opium and cigarette smoking have been identified as significant cancer risk factors. Recently, the International Agency for Research on Cancer (IARC) classified opium as a Group 1 carcinogen in 2020.
Using data from a multicenter case-control study in Iran called IROPICAN, involving 717 cases of bladder cancer and 3477 controls, we assessed the interactions on the causal additive scale between opium use and cigarette smoking and their attributing effects to evaluate public health relevance and test for different mechanistic interaction forms to provide new insights for developing of bladder cancer. A minimally sufficient set of confounders was identified using a causal directed acyclic graph, and the data were analysed employing multiple logistic regression and the inverse probability-of-treatment weighting estimator of the marginal structural linear odds model.
Our findings indicated a significant increase in the risk of bladder cancer associated with concurrent opium use and cigarette smoking (adjusted OR = 6.34, 95 % CI 5.02-7.99; < 0.001), demonstrating a super-additive interaction between these exposures (Weighted RERI = 2.02, 95 % CI 0.47-3.58; = 0.005). The presence of a super-additive interaction suggests that interventions targeting opium users who smoke cigarettes would yield greater benefits compared to non-opium users. Furthermore, there was a mechanistic interaction between two exposures (-value = 0.005) if we assumed two of the exposures have positive monotonic effects, i.e., there must be a sufficient-component cause for developing bladder cancer, which has both opium use and cigarette smoking as components.
There is a causal additive interaction between opium use and cigarette smoking. We observed a super-additive interaction, suggesting the need to focus interventions on specific subgroups. Furthermore, the presence of mechanistic interactions offers profound insights into the mechanisms of cancer induction.
鸦片和吸烟已被确认为重大癌症风险因素。最近，国际癌症研究机构（IARC）在2020年将鸦片列为第1类致癌物。
利用伊朗一项名为IROPICAN的多中心病例对照研究的数据，该研究涉及717例膀胱癌病例和3477名对照，我们在因果相加尺度上评估了鸦片使用与吸烟之间的相互作用及其归因效应，以评估其对公共卫生的相关性，并测试不同的机制相互作用形式，为膀胱癌的发展提供新的见解。使用因果有向无环图确定了一组最小充分混杂因素，并采用多重逻辑回归和边际结构线性优势模型的逆概率治疗加权估计器对数据进行分析。
我们的研究结果表明，同时使用鸦片和吸烟会使膀胱癌风险显著增加（调整后的比值比=6.34，95%置信区间5.02-7.99；P<0.001），表明这些暴露之间存在超相加相互作用（加权相对超额危险度=2.02，95%置信区间0.47-3.58；P=0.005）。超相加相互作用的存在表明，与不使用鸦片的吸烟者相比，针对吸烟的鸦片使用者的干预措施将产生更大的益处。此外，如果我们假设其中两种暴露具有正单调效应，即必须存在一个导致膀胱癌的充分病因组分，且该组分同时包含鸦片使用和吸烟，那么这两种暴露之间存在机制相互作用（P值=0.005）。
鸦片使用与吸烟之间存在因果相加相互作用。我们观察到一种超相加相互作用，这表明需要将干预重点放在特定亚组上。此外，机制相互作用的存在为癌症诱导机制提供了深刻见解。
