癫痫人群丙戊酸暴露与癌症发生风险的相关性分析

doi:10.6040/j.issn.1671-7554.0.2019.1280

摘要/Abstract

摘要： 目的探讨癫痫人群丙戊酸(VPA)暴露与癌症发生风险的相关性。方法通过山东省多中心健康医疗大数据平台获取2012~2017年癫痫人群,分析VPA暴露与非暴露组癌症总发病密度差异与相对危险度(RR);应用Cox模型分析VPA暴露的癌症发生风险比(HR);分析癌症发生风险与VPA暴露时长及处方剂量间的关系。结果通过大数据平台获得2012~2017年癫痫患者3 107例,其中筛选出VPA暴露者1 233例,非暴露者1 788例。暴露与非暴露组分别有27、23例诊断为癌症,癌症总发病密度分别为9.68/1 000(6.03~13.33/1 000)人年、5.70/1 000(3.37~8.03/1 000)人年;剔除卡马西平、苯巴比妥和苯妥英钠3种抗癫痫药物暴露的人群干扰后,暴露与非暴露组癌症总发病密度分别为4.95/1 000(0.10~9.80/1 000)人年、5.25/1 000(2.15~8.35/1 000)人年;经年龄调整后RR为0.79(0.26~2.40),P=0.681,Cox模型调整后HR为0.80(0.25~2.53),P=0.702。筛选暴露时长D≥100且处方剂量P≥10的高暴露剂量人群,癌症总发病密度与暴露时长的χ2线性趋势检验发现,癌症总发病密度的点估计结果随暴露时长增加依次下降,且具有统计学意义(P=0.031);暴露时长按中位数分组的Cox分析得到调整HR为0.59(0.22~1.59),P=0.301;处方剂量按中位数分组的Cox分析得到调整HR为0.93(0.35~2.47),P=0.890。结论未发现VPA具有降低癌症发生风险的作用。

关键词: 癫痫, 丙戊酸, 癌症, 风险比

Abstract: Objective To explore the relationship between valproic acid(VPA)exposure and cancer risk in epileptic population. Methods Patients with epilepsy from 2012 to 2017 were collected from Shandong Multi-Center Healthcare Big-Data. Total incidence of cancer in VPA exposed and unexposed groups were analyzed, and the relative risk(RR)was calculated. The Hazard ratio(HR)was analyzed with Cox model. Correlations between cancer risk and duration of VPA exposure(D)and prescription dose of VPA exposure(P)were analyzed. Results A total of 3 107 people with epilepsy were collected, including 1 233 VPA exposed and 1 788 unexposed. Cancer was detected in 27 and 23 cases in the exposed and unexposed groups, respectively, and the total incidence of cancer was 9.68/1 000(6.03-13.33/1 000)person/year, and 5.70/1 000(3.37-8.03/1000)person/year, respectively. After exposures to carbamazepine, phenobarbital and phenytoin were excluded, the total incidence of cancer in VPA exposed and unexposed group was 4.95/1 000(0.10-9.80/1 000)person/year, and 5.25/1 000(2.15-8.35/1 000)person/year, respectively. After age was adjusted, the RR was 0.79(0.26-2.40), P=0.681. After Cox model was adjusted, HR was 0.80(0.25-2.53), P=0.702. For population with high VPA exposure(D≥100 and P≥10), the incidence of cancer significantly decreased with the increase of duration of exposure(P=0.031). After grouping based on the median duration of VPA exposure, the adjusted HR was 0.59(0.22-1.59), P=0.301. After grouping based on the median of the prescription dose of VPA, the adjusted HR was 0.93(0.35-2.47), P=0.890. Conclusion VPA is not associated with a significant reduction in cancer risk.

Key words: Epilepsy, Valproic acid, Cancer, Hazard ratio

中图分类号:

R730.1

王振东,丁稳稳,凤志慧. 癫痫人群丙戊酸暴露与癌症发生风险的相关性分析[J]. 山东大学学报 (医学版), 2020, 58(4): 110-117.

WANG Zhendong, DING Wenwen, FENG Zhihui. Correlation between valproic acid exposure and cancer risk in epileptic population[J]. Journal of Shandong University (Health Sciences), 2020, 58(4): 110-117.

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