Journal of Shandong University (Health Sciences) ›› 2020, Vol. 58 ›› Issue (4): 110-117.doi: 10.6040/j.issn.1671-7554.0.2019.1280

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Correlation between valproic acid exposure and cancer risk in epileptic population

WANG Zhendong, DING Wenwen, FENG Zhihui   

  1. Department of Occupational and Environmental Health, School of Public Health, Shandong University, Jinan 250012, Shandong, China
  • Published:2022-09-27

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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

CLC Number: 

  • R730.1
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