title: Association of multiple drug resistance-1 gene polymorphism with multiple drug resistance in breast cancer patients from an ethnic Saudi Arabian population.
abstract: Chemotherapy has been used widely to treat cancer, both as a systemic therapy and as a local treatment. Unfortunately, many types of cancer are still refractory to chemotherapy. The mechanisms of anticancer drug resistance have been extensively explored but have not been fully characterized. This study analyzed the occurrences of polymorphism (SNP) in the MDR1 gene in breast cancer patients and determined a possible association with chemotherapy. The study group included one hundred breast carcinoma patients who subsequently received chemotherapy (the regimen generally consisted of commonly used drugs such as cyclophosphamide, adriamycin, 5-fluorouracil, docetaxel and their combinations). Blood samples from 100 healthy individuals are used, as controls were also genotyped for the MDR1 gene. This investigation revealed a significant correlation with response to various regimens of chemotherapy showing a low response to therapy with the CT/TT genotype at (exon 12) 1236 codon (p<0.001). These findings demonstrate, for the first time, that the polymorphisms in (exon 12) 1236 codon of the MDR1 gene greatly influence the drug response in patients from the Arab population of Saudi Arabia.
authors.affiliation: Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Abdulaziz A
authors.initials: AA
authors.lastname: Alsaif
authors.forename: Tarique N
authors.initials: TN
authors.lastname: Hasan
authors.forename: Gowhar
authors.initials: G
authors.lastname: Shafi
authors.forename: Naveed A
authors.initials: NA
authors.lastname: Syed
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Alsaif
authors.forename: Abdullah H
authors.initials: AH
authors.lastname: Al-Assaf
authors.forename: Ali A
authors.initials: AA
authors.lastname: Alshatwi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D003062:Codon; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012529:Saudi Arabia
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003062:Codon
keywords: 5-Fluorouracil; Adriamycin; Biomarker; Breast cancer; Chemotherapy; Cyclophosphamide; Docetaxel; Drug resistance; MDR1 gene; SNP