Abstract

The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered 32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano-Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study.

Highlights

  • The Plurinational State of Bolivia (Bolivia) lies west of the Andes and has a high incidence of gallbladder cancer (GBC) (Orth and Beger, 2000; Moore et al, 2014)

  • The frequency of the glutathione S-transferase mu 1 (GSTM1) null genotype was significantly higher in GBC patients than in the healthy subjects

  • No significant differences were found for the cytochrome P450 1A1 (CYP1A1) rs1048943, GSTT1, or tumor suppressor protein p53 (TP53) rs1042522 polymorphisms

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Summary

Introduction

The Plurinational State of Bolivia (Bolivia) lies west of the Andes and has a high incidence of gallbladder cancer (GBC) (Orth and Beger, 2000; Moore et al, 2014). Strom et al reported that, in addition to race (i.e., Aymara speakers), risk factors for GBC in Bolivians were body mass index, family history of gallstones, typhoid fever infection, and food consumption habits (Strom et al, 1995). These well-known environmental risk factors for GBC are not specific to Bolivians. Asai et al reported that GBC development in Bolivians was related to genetic and environmental factors, mutations in tumor protein p53 (TP53) and K-ras (Asai et al, 2014). Both environmental and genetic factors are important in GBC development in Bolivians

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