title: Multidrug resistance protein 2 genetic polymorphism and colorectal cancer             recurrence in patients receiving adjuvant FOLFOX-4 chemotherapy.
abstract: Multidrug resistance protein 2 (MRP2), encoded by the ATP-binding cassette C2 (ABCC2) gene, is an efflux pump located on the apical membrane of many polarized cells, which transports conjugate compounds by an ATP-dependent mechanism. The correlation of G1249A ABCC2 polymorphism with the development of colorectal cancer (CRC) and poor prognosis was evaluated in patients who were treated with fluorouracil/-leucovorin (FL) plus oxaliplatin (FOLFOX-4). A total of 50 paraffin‑embedded tissue samples collected from CRC patients were analyzed to identify the polymorphism. Patients were in stage II/III and received postoperative FOLFOX-4 chemotherapy. As a control group, an equal number of unrelated healthy subjects were enrolled in the study. The polymorphism was genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and results were compared with clinicopathological markers, early relapse and survival rates. During the 12 months of follow-up, local and distant recurrences were observed in 15 (30%) patients. No significant difference in the distribution of wild-type and polymorphic genotypes was observed between the patient and control groups and between the patients who experienced recurrence within 1 year and those who did not (all P>0.05). In conclusion, the G1249A polymorphism is not associated with CRC risk and early recurrence. However, significant correlation was observed between G1249A polymorphism and the overall survival and disease-free survival of the patients.
authors.affiliation: Department of Pathology, Faculty of Medicine and Health Sciences,                     University Putra Malaysia, Serdang, Selangor 43400, Malaysia.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Mirakhorli
authors.forename: Sabariah Abdul
authors.initials: SA
authors.lastname: Rahman
authors.forename: Syahrilnizam
authors.initials: S
authors.lastname: Abdullah
authors.forename: Masoud
authors.initials: M
authors.lastname: Vakili
authors.forename: Reza
authors.initials: R
authors.lastname: Rozafzon
authors.forename: Ahad
authors.initials: A
authors.lastname: Khoshzaban
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D000077150:Oxaliplatin; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult
chemical_list: D005472:Fluorouracil; D002955:Leucovorin; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C000715087:ABCC2 protein, human