Cancer Epidemiology and Health Services Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK.
Academic Primary Care, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
Aliment Pharmacol Ther. 2018 Jul;48(1):55-64. doi: 10.1111/apt.14796. Epub 2018 May 9.
Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly used. PPIs have been shown to promote liver cancer in rats; however, only one study has examined the association in humans.
To investigate PPIs and H2RAs and risk of primary liver cancer in two large independent study populations.
We conducted a nested case-control study within the Primary Care Clinical Informatics Unit (PCCIU) database in which up to five controls were matched to cases with primary liver cancer, recorded by General Practitioners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations with prescribed PPIs and H2RAs were calculated using conditional logistic regression. We also conducted a prospective cohort study within the UK Biobank using self-reported medication use and cancer-registry recorded primary liver cancer. Hazard ratios (HRs) and 95% CIs were calculated using Cox regression.
In the PCCIU case-control analysis, 434 liver cancer cases were matched to 2103 controls. In the UK Biobank cohort, 182 of 475 768 participants developed liver cancer. In both, ever use of PPIs was associated with increased liver cancer risk (adjusted OR 1.80, 95% CI 1.34, 2.41 and adjusted HR 1.99, 95% CI 1.34, 2.94 respectively). There was little evidence of association with H2RA use (adjusted OR 1.21, 95% CI 0.84, 1.76 and adjusted HR 1.70, 95% CI 0.82, 3.53 respectively).
We found some evidence that PPI use was associated with liver cancer. Whether this association is causal or reflects residual confounding or reverse causation requires additional research.
质子泵抑制剂 (PPIs) 和组胺-2 受体拮抗剂 (H2RAs) 被广泛使用。PPIs 已被证明会在大鼠中促进肝癌的发生；然而，只有一项研究在人类中研究了这种关联。
在两个大型独立研究人群中调查 PPIs 和 H2RAs 与原发性肝癌的风险。
我们在初级保健临床信息单位 (PCCIU) 数据库中进行了一项嵌套病例对照研究，其中多达 5 名对照与由全科医生记录的原发性肝癌病例相匹配。使用条件逻辑回归计算与处方 PPIs 和 H2RAs 相关的比值比 (OR) 和 95%置信区间 (95%CI)。我们还在英国生物库中使用自我报告的药物使用和癌症登记记录的原发性肝癌进行了前瞻性队列研究。使用 Cox 回归计算风险比 (HR) 和 95%CI。
在 PCCIU 病例对照分析中，434 例肝癌病例与 2103 例对照相匹配。在英国生物库队列中，475768 名参与者中有 182 人患上了肝癌。在这两种情况下，PPIs 的使用均与肝癌风险增加相关（调整后的 OR 为 1.80，95%CI 为 1.34-2.41 和调整后的 HR 为 1.99，95%CI 为 1.34-2.94）。使用 H2RA 的证据很少（调整后的 OR 为 1.21，95%CI 为 0.84-1.76 和调整后的 HR 为 1.70，95%CI 为 0.82-3.53）。
我们发现一些证据表明 PPI 的使用与肝癌有关。这种关联是因果关系还是反映了残余混杂或反向因果关系，需要进一步研究。
