The Investigation of Associations between TP53 rs1042522, BBC3 rs2032809, CCND1 rs9344, EGFR rs2227983 Polymorphisms and Breast Cancer Phenotype and Prognosis.

Justina Bekampytė,Aistė Savukaitytė,Agnė Bartnykaitė,Jurgita Gudaitienė,Erika Korobeinikova,Rasa Ugenskienė,Elona Juozaitytė

doi:10.3390/diagnostics11081419

Abstract

Breast cancer is one of the most common oncological diseases among women worldwide. Cell cycle and apoptosis—related genes TP53, BBC3, CCND1 and EGFR play an important role in the pathogenesis of breast cancer. However, the roles of single nucleotide polymorphisms (SNPs) in these genes have not been fully defined. Therefore, this study aimed to analyze the association between TP53 rs1042522, BBC3 rs2032809, CCND1 rs9344 and EGFR rs2227983 polymorphisms and breast cancer phenotype and prognosis. For the purpose of the analysis, 171 Lithuanian women were enrolled. Genomic DNA was extracted from peripheral blood; PCR-RFLP was used for SNPs analysis. The results showed that BBC3 rs2032809 was associated with age at the time of diagnosis, disease progression, metastasis and death. CCND1 rs9344 was associated with tumor size, however an association resulted in loss of significance after Bonferroni correction. In survival analysis, significant associations were observed between BBC3 rs2032809 and OS, PFS and MFS. EGFR rs2227983 also showed some associations with OS and PFS (univariate Cox regression analysis). However, the results were in loss of significance (multivariate Cox regression analysis). In conclusion, BBC3 rs2032809 polymorphism was associated with breast cancer phenotype and prognosis. Therefore, it could be applied as potential markers for breast cancer prognosis.

Highlights

Breast cancer is one of the most common cancers and the second leading cause of cancer-related deaths among women worldwide
Single nucleotide polymorphisms (SNPs), located in genes, which code proteins involved in the regulation of cell cycle and apoptosis, can cause dysregulation of essential cellular processes by affecting protein expression or activity resulting in uncontrolled cell growth [3]
Our results showed that 67.8% and 59.1% of patients were positive for ER and PR, respectively, while human epidermal growth factor receptor 2 (HER2) expression was found only in 18.7% of cases

Summary

Introduction

Breast cancer is one of the most common cancers and the second leading cause of cancer-related deaths among women worldwide. Diagnosis is an important approach leading to good prognosis and a high survival rate. The morbidity and mortality from breast cancer are still high. The investigation of new prognostic factors is necessary for breast cancer patients [1,2]. Single nucleotide polymorphisms (SNPs), located in genes, which code proteins involved in the regulation of cell cycle and apoptosis, can cause dysregulation of essential cellular processes by affecting protein expression or activity resulting in uncontrolled cell growth [3]. Previous studies indicated that TP53, BBC3, CCND1 and EGFR genes play important roles in the pathogenesis of breast cancer [4,5,6,7]. The roles of most SNPs in these genes have not been fully defined

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