J Cancer 2019; 10(13):2915-2926. doi:10.7150/jca.31130

Research Paper

Glutathione S-transferases genes variants and chemotherapy efficacy in gastrointestinal cancer patients: a meta-analysis based on 50 pharmacogenetic studies

Yuesheng Sun1, Jianghua Pan1, Xiaochun Tong1, Ende Chen1, Wangxin Yan1, Mengpei Wu2, Qiang Qu3,✉, Jian Qu4,✉

1. Department of General Surgery, The Third Clinical College of Wenzhou Medical University, Wenzhou People 's Hospital, Wenzhou, 325000, People's Republic of China
2. Department of General Surgery, Taishun People's Hospital, Wenzhou, 325000, People's Republic of China
3. Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410078, People's Republic of China
4. Department of Pharmacy, the Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University, Changsha 410011, People's Republic of China.

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Citation:
Sun Y, Pan J, Tong X, Chen E, Yan W, Wu M, Qu Q, Qu J. Glutathione S-transferases genes variants and chemotherapy efficacy in gastrointestinal cancer patients: a meta-analysis based on 50 pharmacogenetic studies. J Cancer 2019; 10(13):2915-2926. doi:10.7150/jca.31130. Available from http://www.jcancer.org/v10p2915.htm

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Abstract

Background: The role of glutathione s-transferase genes (GSTP1, GSTM1 and GSTT1) variants and the GSTP1 expression level on chemotherapy efficacy of gastrointestinal cancer (GIC) patients were inconsistent.

Methods: A meta-analysis about GSTP1, GSTM1 and GSTT1 variants and the GSTP1 expression level on chemotherapy efficacy of GIC patients was performed using data from PubMed, PMC, EMBASE, Web of Science, and Wanfang database.

Results: Our meta-analysis enrolled 50 publications including 6518 patients. We found that patients with GIC harboring GSTP1 (IIe105Val) Val locus had higher objective response rates (ORR) than the IIe/IIe genotypic patients (odds ratio (OR) = 1.580, 95% confidence interval (CI) = 1.159-2.154, P = 0.004). Significant associations were found between the Ile105Val variant and overall survival of Caucasian GIC patients (IIe/Val vs. IIe/IIe: OR = 0.797 (0.674-0.944), P = 0.009). Caucasian GIC patients and gastric cancer patients with GSTT1 null genotype had worse response rates compared to GSTT1 present patients (OR = 0.530 (0.356-0.789), P = 0.002; OR = 0.643 (0.463-0.895), P = 0.009, respectively).

Conclusion: This meta-analysis illustrates that GSTP1 IIe105Val and GSTT1 null/present variants could be useful predictors of chemotherapy efficacy in patients with gastrointestinal cancer.

Keywords: gastrointestinal cancer, glutathione S-transferases genes, variants, chemotherapy, efficacy