Cancer Epidemiology and Health Services Research Group, Centre for Public Health, Queen's University Belfast, Belfast, BT12 6BA, UK.
School of Pharmacy, Queen's University Belfast, Belfast, BT9 7BL, UK.
Pharmacoepidemiol Drug Saf. 2019 Apr;28(4):460-470. doi: 10.1002/pds.4688. Epub 2018 Nov 20.
Preclinical studies show statins inhibit pathways involved in gastric cancer progression, with observational studies demonstrating reduced gastric cancer risk in statin users. However, few studies have investigated statin use and survival in gastric cancer. We investigated statin use and survival in two large population-based gastric cancer cohorts.
Patients diagnosed with gastric cancer from 1998 to 2012 were identified from English and Scottish cancer registries. Statin prescriptions were identified from linkages to the UK Clinical Practice Research Datalink in England and the Prescribing Information System in Scotland, and deaths identified from national mortality records. Time-dependent Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) for cancer-specific mortality by statin use in multivariate analysis. Meta-analysis techniques pooled results across the cohorts.
The combined cohorts contained 3833 patients with gastric cancer and 2392 cancer-specific deaths. Statin use after diagnosis was associated with reduced cancer-specific mortality (adjusted HR 0.83; 95% CI, 0.74-0.92). HRs for less than 1 year and over 1 year of statin use were similar (adjusted HR 0.83; 95% CI, 0.73-0.94 and adjusted HR 0.83; 95% CI, 0.64-1.01, respectively). Statin use prior to diagnosis was also associated with reduced cancer-specific mortality (adjusted HR 0.91; 95% CI, 0.84-0.98).
In two independent UK cohorts, there was some evidence that statin use was associated with reduced cancer-specific mortality. However, these associations were weak in magnitude and did not follow a clear dose response, and we cannot rule out confounding by stage.
临床前研究表明,他汀类药物可抑制胃癌进展相关的途径,观察性研究表明,他汀类药物使用者的胃癌风险降低。然而,很少有研究调查过他汀类药物的使用与胃癌患者的生存情况。我们调查了两项大型基于人群的胃癌队列研究中他汀类药物的使用与生存情况。
从英国和苏格兰癌症登记处确定了 1998 年至 2012 年间诊断为胃癌的患者。在英格兰的英国临床实践研究数据链接和苏格兰的处方信息系统中确定了他汀类药物的处方,从国家死亡率记录中确定了死亡情况。使用时间依赖性 Cox 回归模型,在多变量分析中计算了按他汀类药物使用情况的癌症特异性死亡率的危险比(HR)和 95%置信区间(CI)。荟萃分析技术汇总了两个队列的结果。
联合队列包含 3833 例胃癌患者和 2392 例癌症特异性死亡患者。诊断后使用他汀类药物与降低癌症特异性死亡率相关(调整后的 HR 为 0.83;95%CI,0.74-0.92)。使用他汀类药物不到 1 年和超过 1 年的 HR 相似(调整后的 HR 分别为 0.83;95%CI,0.73-0.94 和调整后的 HR 0.83;95%CI,0.64-1.01)。诊断前使用他汀类药物也与降低癌症特异性死亡率相关(调整后的 HR 为 0.91;95%CI,0.84-0.98)。
在两个独立的英国队列中,有一些证据表明他汀类药物的使用与降低癌症特异性死亡率有关。然而,这些关联的幅度较弱,且没有遵循明确的剂量反应关系,我们不能排除与分期有关的混杂因素。