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Article

Role of Genetic Variation in Cytochromes P450 in Breast Cancer Prognosis and Therapy Response

1
Toxicogenomics Unit, National Institute of Public Health, 100 00 Prague, Czech Republic
2
Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 301 00 Pilsen, Czech Republic
3
Department of Oncosurgery, MEDICON, 140 00 Prague, Czech Republic
4
Department of Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, 150 00 Prague, Czech Republic
5
Comprehensive Cancer Center Novy Jicin, Hospital Novy Jicin, 741 01 Novy Jicin, Czech Republic
6
Department of Surgery, EUC Hospital Zlin and Tomas Bata University in Zlin, 763 02 Zlin, Czech Republic
*
Author to whom correspondence should be addressed.
Academic Editor: Irmgard Tegeder
Int. J. Mol. Sci. 2021, 22(6), 2826; https://doi.org/10.3390/ijms22062826
Received: 10 February 2021 / Revised: 5 March 2021 / Accepted: 8 March 2021 / Published: 10 March 2021
(This article belongs to the Collection Feature Papers in Molecular Biology)
Breast cancer is the most frequent cancer in the female population worldwide. The role of germline genetic variability in cytochromes P450 (CYP) in breast cancer prognosis and individualized therapy awaits detailed elucidation. In the present study, we used the next-generation sequencing to assess associations of germline variants in the coding and regulatory sequences of all human CYP genes with response of the patients to the neoadjuvant cytotoxic chemotherapy and disease-free survival (n = 105). A total of 22 prioritized variants associating with a response or survival in the above evaluation phase were then analyzed by allelic discrimination in the large confirmation set (n = 802). Associations of variants in CYP1B1, CYP4F12, CYP4X1, and TBXAS1 with the response to the neoadjuvant cytotoxic chemotherapy were replicated by the confirmation phase. However, just association of variant rs17102977 in CYP4X1 passed the correction for multiple testing and can be considered clinically and statistically validated. Replicated associations for variants in CYP4X1, CYP24A1, and CYP26B1 with disease-free survival of all patients or patients stratified to subgroups according to therapy type have not passed a false discovery rate test. Although statistically not confirmed by the present study, the role of CYP genes in breast cancer prognosis should not be ruled out. In conclusion, the present study brings replicated association of variant rs17102977 in CYP4X1 with the response of patients to the neoadjuvant cytotoxic chemotherapy and warrants further research of genetic variation CYPs in breast cancer. View Full-Text
Keywords: breast cancer; cytochrome P450; therapy; response; survival; prognosis; next-generation sequencing breast cancer; cytochrome P450; therapy; response; survival; prognosis; next-generation sequencing
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MDPI and ACS Style

Hlaváč, V.; Václavíková, R.; Brynychová, V.; Ostašov, P.; Koževnikovová, R.; Kopečková, K.; Vrána, D.; Gatěk, J.; Souček, P. Role of Genetic Variation in Cytochromes P450 in Breast Cancer Prognosis and Therapy Response. Int. J. Mol. Sci. 2021, 22, 2826. https://doi.org/10.3390/ijms22062826

AMA Style

Hlaváč V, Václavíková R, Brynychová V, Ostašov P, Koževnikovová R, Kopečková K, Vrána D, Gatěk J, Souček P. Role of Genetic Variation in Cytochromes P450 in Breast Cancer Prognosis and Therapy Response. International Journal of Molecular Sciences. 2021; 22(6):2826. https://doi.org/10.3390/ijms22062826

Chicago/Turabian Style

Hlaváč, Viktor, Radka Václavíková, Veronika Brynychová, Pavel Ostašov, Renata Koževnikovová, Katerina Kopečková, David Vrána, Jiří Gatěk, and Pavel Souček. 2021. "Role of Genetic Variation in Cytochromes P450 in Breast Cancer Prognosis and Therapy Response" International Journal of Molecular Sciences 22, no. 6: 2826. https://doi.org/10.3390/ijms22062826

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