Study of the potential association of the BCHE rs1803274 genetic polymorphism and serum level of its protein with breast cancer

Abstract

Background

Genetic-based individual differences remain a promising area for studying cancer susceptibility. BCHE gene encodes the butyrylcholinesterase (BChE) enzyme, which has been linked to inflammation and tumor genesis. The commonest missense mutation of BCHE gene is the rs1803274 G/A polymorphism. We aimed to analyze BCHE rs1803274 gene polymorphism in terms of distribution among breast cancer patients, its effect on enzyme activity and its correlation with clinic pathological parameters.

Methods

160 breast cancer female patients matched by age with 120 female healthy controls were recruited. CA 15–3 and CEA were measured by ELISA. BChE activity was measured by spectrophotometry. BCHE rs1803274 polymorphism was analyzed by real time- PCR.

Results

Significant higher prevalence of GA genotype and A allele were observed in patients [P < 0.001, OR (95% CI); 3.12 (1.67–5.85), P < 0.001, OR (95% CI); 2.86 (1.68–4.87) respectively]. This significance was observed under the dominant mode of inheritance (P < 0.001, OR (95% CI); 3.22 (1.78–5.85). GA + AA patients showed significant association with tumor grade, stage, and metastasis (P < 0.001). GA + AA patients exhibited significantly lower BChE activity compared to GG patients (3648.5 (2968–4332) mU/ml and 7128.5 (6332–8341) mU/ml respectively, P < 0.001).

Conclusions

Higher frequency of the A-variant of BCHE rs1803274 and the associated low activity of BChE in breast cancer patients could represent susceptibility elements for development of breast cancer. Moreover, the rs1803274 is linked to some tumor features, which could be a proof of its prognostic value.