title: Non-coding polymorphisms in nucleotide binding domain 1 in ABCC1 gene associate with transcript level and survival of patients with breast cancer.
abstract: OBJECTIVE
  ATP-Binding Cassette (ABC) transporters may cause treatment failure by transporting of anticancer drugs outside of the tumor cells. Multidrug resistance-associated protein 1 coded by the ABCC1 gene has recently been suggested as a potential prognostic marker in breast cancer patients. This study aimed to explore tagged haplotype covering nucleotide binding domain 1 of ABCC1 in relation with corresponding transcript levels in tissues and clinical phenotype of breast cancer patients.
  
  
  METHODS
  The distribution of twelve ABCC1 polymorphisms was assessed by direct sequencing in peripheral blood DNA (n = 540).
  
  
  RESULTS
  Tumors from carriers of the wild type genotype in rs35623 or rs35628 exhibited significantly lower levels of ABCC1 transcript than those from carriers of the minor allele (p = 0.003 and p = 0.004, respectively). The ABCC1 transcript levels significantly increased in the order CT-GT>CC-GT>CC-GG for the predicted rs35626-rs4148351 diplotype. Chemotherapy-treated patients carrying the T allele in rs4148353 had longer disease-free survival than those with the GG genotype (p = 0.043). On the other hand, hormonal therapy-treated patients with the AA genotype in rs35628 had significantly longer disease-free survival than carriers of the G allele (p = 0.012).
  
  
  CONCLUSIONS
  Taken together, our study shows that genetic variability in the nucleotide binding domain 1 has a significant impact on the ABCC1 transcript level in the target tissue and may modify survival of breast cancer patients.
authors: Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic; 3rd Faculty of Medicine, Charles University, Prague, Czech Republic.
authors: Tereza
authors: T
authors: Kunická
authors: Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic.
authors: Radka
authors: R
authors: Václavíková
authors: Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic; 3rd Faculty of Medicine, Charles University, Prague, Czech Republic.
authors: Viktor
authors: V
authors: Hlaváč
authors: Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic; Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic.
authors: David
authors: D
authors: Vrána
authors: Institute for the Care for Mother and Child, Prague, Czech Republic.
authors: Václav
authors: V
authors: Pecha
authors: Institute for the Care for Mother and Child, Prague, Czech Republic.
authors: Karel
authors: K
authors: Rauš
authors: Biolab Praha, k.s., Prague, Czech Republic.
authors: Markéta
authors: M
authors: Trnková
authors: Department of Oncology, Motol University Hospital, Prague, Czech Republic.
authors: Kateřina
authors: K
authors: Kubáčková
authors: Department of Radiotherapy and Oncology, Faculty Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors: Miloslav
authors: M
authors: Ambruš
authors: Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic; Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic.
authors: Ludmila
authors: L
authors: Vodičková
authors: Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors: Pavel
authors: P
authors: Vodička
authors: Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic.
authors: Pavel
authors: P
authors: Souček
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C421109:multidrug resistance-associated protein 1