Role of Genetic Variation in ABC Transporters in Breast Cancer Prognosis and Therapy Response

International Journal of Molecular Sciences

David Vrána¹  Katerina Kopečková²  Renata Koževnikovová³  Jiří Gatěk⁴  Viktor Hlaváč⁵  Radka Václavíková⁵  Veronika Brynychová⁵  Pavel Souček⁵ 

[1] Department of Oncology, Palacky University Medical School and Teaching Hospital, 779 00 Olomouc, Czech Republic;Department of Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, 150 06 Prague, Czech Republic;Department of Oncosurgery, Medicon Services, 140 00 Prague, Czech Republic;Department of Surgery, EUC Hospital and University of Tomas Bata in Zlin, 760 01 Zlin, Czech Republic;Toxicogenomics Unit, National Institute of Public Health, 100 42 Prague, Czech Republic;

关键词: ABC transporter;    therapy response;    disease-free survival;    breast cancer;    next-generation sequencing;    competitive allele-specific PCR;   

DOI  :  10.3390/ijms21249556

来源: DOAJ

【 摘 要 】

Breast cancer is the most common cancer in women in the world. The role of germline genetic variability in ATP-binding cassette (ABC) transporters in cancer chemoresistance and prognosis still needs to be elucidated. We used next-generation sequencing to assess associations of germline variants in coding and regulatory sequences of all human ABC genes with response of the patients to the neoadjuvant cytotoxic chemotherapy and disease-free survival (n = 105). A total of 43 prioritized variants associating with response or survival in the above testing phase were then analyzed by allelic discrimination in the large validation set (n = 802). Variants in ABCA4, ABCA9, ABCA12, ABCB5, ABCC5, ABCC8, ABCC11, and ABCD4 associated with response and variants in ABCA7, ABCA13, ABCC4, and ABCG8 with survival of the patients. No association passed a false discovery rate test, however, the rs17822931 (Gly180Arg) in ABCC11, associating with response, and the synonymous rs17548783 in ABCA13 (survival) have a strong support in the literature and are, thus, interesting for further research. Although replicated associations have not reached robust statistical significance, the role of ABC transporters in breast cancer should not be ruled out. Future research and careful validation of findings will be essential for assessment of genetic variation which was not in the focus of this study, e.g., non-coding sequences, copy numbers, and structural variations together with somatic mutations.

【 授权许可】

Unknown