The Role of Matrix Metalloproteinase Single-Nucleotide Polymorphisms in the Clinicopathological Properties of Breast Cancer.

(1) Background. Breast cancer is the leading cancer type among women. Despite convenient diagnostics at early stages, there is a need for continuous monitoring to predict more aggressive or recurring breast cancer forms. The evidence suggests that the detection of genetic biomarkers could help in improving disease management and reduce mortality. Matrix metalloproteinases (MMPs) are a large family of enzymes that perform physiologically relevant functions and have the potential properties to be biomarkers for cancer assessment. We aimed to evaluate the contribution and association of single-nucleotide polymorphisms (SNPs) in MMP genes (MMP1, MMP2, MMP3, MMP7, MMP8, MMP9) with clinicopathological breast-cancer features. (2) Methods. In this study, 100 breast cancer patients were genotyped by polymerase chain reaction-restriction fragment length polymorphism methodology (PCR-RFLP). (3) Results. The presence of the MMP7 rs11568818 A allele was associated with lower chances for poorly differentiated breast cancer. The lower possibility for HER2-positive breast cancer was associated with the presence of the MMP9 rs3918242 C allele. (4) Conclusions. These results indicate that MMP7 rs11568818 and MMP9 rs3918242 are potential biomarkers for the anticipation of breast cancer aggressiveness.

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

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.

The role of functional polymorphisms in oxidative stress-related genes on early-stage breast cancer survival.

BACKGROUND: Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer. METHODS: The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I-II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays. RESULTS: The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size (P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status (P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048). CONCLUSION: Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.

The impact of mitochondria-related POLG and TFAM variants on breast cancer pathomorphological characteristics and patient outcomes.

PURPOSE: Breast cancer is the most frequent female cancer, leading to relapse with distant metastasis of approximately one-third of patients. Cancer is usually considered a genetic disease involving mutations in nuclear DNA. However, genes, coding for mitochondrial proteins or regulatory molecules, are rarely under consideration. This study aimed to analyse 10 single nucleotide variants in POLG and TFAM genes and assess their association with tumour phenotype and disease outcome. MATERIALS AND METHODS: A total of 234 breast cancer patients were included in this study. Variations were determined with Real-Time PCR using TaqMan® probes. RESULTS: We found that patients with POLG rs2307441 TT and CT genotypes had a lower probability for vascular invasion than those with CC genotype (p = 0.001). Patients with POLG rs2072267 AG genotype were predisposed for progression compared with GG genotype (p = 0.015). TFAM rs3900887 TT genotype was associated with a higher probability for positive oestrogen receptors (p = 0.003) and lymphatic invasion (p = 0.001) in comparison to AA genotype, patients with TT (p = 0.000) were more likely to have positive lymph nodes. CONCLUSIONS: Our data suggest that variations in POLG and TFAM genes are important determinacies of tumour phenotype and disease outcome in breast cancer patients.

Associations of MDM2 and MDM4 Polymorphisms with Early-Stage Breast Cancer.

Breast cancer is one of the most common cancers worldwide. Single nucleotide polymorphisms (SNPs) in MDM2 and MDM4 have been associated with various cancers. However, the influence on clinical characteristics of breast cancer has not been sufficiently investigated yet. Thus, this study aimed to investigate the relationship between SNPs in MDM2 (rs2279744, rs937283, rs937282) and MDM4 (rs1380576, rs4245739) and I-II stage breast cancer. For analysis, the genomic DNA was extracted from 100 unrelated women peripheral blood. Polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The study showed that MDM2 rs937283 and rs937282 were significantly associated with estrogen receptor status and human epidermal growth factor receptor 2 (HER2) status. SNPs rs1380576 and rs4245739, located in MDM4, were significantly associated with status of estrogen and progesterone receptors. Our findings suggest that rs937283 AG, rs937282 CG, rs1380576 CC, and rs4245739 AA genotypes were linked to hormonal receptor positive breast cancer and may be useful genetic markers for disease assessment.