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

Abstract

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.

Keywords:

• TFAM
• POLG
• SNV
• breast cancer
• tumour phenotype
• outcome

Acknowledgments

The authors acknowledge our gratitude to patients included in this study. The authors thank The Research foundation of Lithuanian University of Health Sciences. The authors thank Ruta Insodaite for excellent technical assistance.

Ethics approval and consent to participate

This study was approved by the Kaunas Regional Biomedical Research Ethics Committee (Protocol no. BE-2-10 and P1-BE-2-10/2014). The written informed consent following the detailed explanation was obtained and blood samples were collected from each patient. All experiments comply with the current laws of the country in which they were performed.

Author contributions

RU, EJ and IG contributed to design and planning. IG contributed to experimental procedures. EJ, EK, JG, DV and LP contributed to data collection. IG and RU contributed to the writing the manuscript. All authors contributed to approval and correcting the final version of the manuscript.

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

This work was supported by the Lithuanian University of Health Sciences.