Mutational and Expressional Deregulation of the CHEK1 Gene in Breast Cancer Patients

Breast cancer burden is increasing day by day. The identification of novel genetic markers based on polymorphism and expression analysis is necessary to reduce the suffering of patients.

The current study is divided into two parts; firstly, the possible association of hotspot CHEK1 gene single nucleotide polymorphisms (SNPs) was investigated in breast cancer patients. Secondly, the relative expression of CHEK1 gene was assessed at the mRNA level.

For SNP analysis 500 breast cancer patients and 500 controls were used. Tetra Amplification-Refractory Mutation System (ARMS) PCR was used for screening of the selected polymorphisms. Expression profiling of the CHEK1 gene was assessed in 200 breast tumors along with their adjacent uninvolved healthy tissue using quantitative real time (RT) PCR.

Data analysis showed that mutant genotype of selected SNPs (rs521102, p < 0.002; rs284722, p < 0.001 and rs35817404, p < 0.0001) of the CHEK1 gene showed significant association with increased tumorigenesis risk among patients compared to healthy controls. The relative expression analysis of the selected gene showed significant downregulation of the CHEK1 gene (p < 0.0001) in breast tumor tissues as compared to adjacent control tissues.

Based on the current findings we can conclude that genetic/expression deregulation of the CHEK1 gene play an important role in increased breast cancer risk. The CHEK1 gene also plays an important role in chemotherapy resistance response among the Pakistani population.