Prognostic value of the multidrug resistance transporter ABCG2 gene polymorphisms in Chinese patients with de novo acute leukaemia

• Published in: European journal of cancer (1990) 2011-09, Vol.47 (13), p.1990-1999
• Main Authors: Wang, Fang, Liang, Yong-ju, Wu, Xing-ping, Chen, Li-ming, To, Kenneth Kin Wah, Dai, Chun-ling, Yan, Yan-yan, Wang, Yan-sheng, Tong, Xiu-zhen, Fu, Li-wu
• Format: Article
• Language: English
• Subjects: ABCG2; Acute Disease; Acute leukaemia; Adolescent; Adult; Aged; Animals; ATP Binding Cassette Transporter, Sub-Family G, Member 2; ATP-Binding Cassette Transporters - biosynthesis; ATP-Binding Cassette Transporters - genetics; Base Sequence; Biological and medical sciences; Bone Marrow Transplantation; Cell Line, Tumor; Child; Child, Preschool; China; Drug Resistance, Neoplasm; Female; Hematology, Oncology and Palliative Medicine; Humans; Leukemia - genetics; Leukemia - metabolism; Leukemia - surgery; Male; Medical sciences; Mice; Middle Aged; Molecular Sequence Data; Multidrug resistance; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Pharmacology. Drug treatments; Polymerase Chain Reaction; Polymorphism; Polymorphism, Single Nucleotide; Prognosis; Tumors; Young Adult
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2011.03.032

Abstract Background Functional polymorphisms of the ABCG2 gene may contribute to individual variability in drug response and the prognosis of patients. Methods In the present study, the genetic polymorphisms and expression of ABCG2 were analysed in blasts cells obtained from 184 Chinese patients with de novo acute leukaemia to investigate their possible association with clinical outcomes. Results A novel synonymous ABCG2-single nucleotide polymorphism (SNP) at exon 16 (13561218 C/T) and five known SNPs at exon 2 (13608835 G/A), exon 5 (13600044 C/A), intron 10 (13576005 C/T), intron 13 (13564503 C/T) and intron 14 (13563578 A/G) were identified with occurrence rates of 1.1%, 64.1%, 30.4%, 21.2%, 39.7% and 28.8%, respectively. We found that patients with the ABCG2 34GG genotype displayed longer disease free survival (DFS) ( P < 0.001) and overall survival (OS) ( P < 0.001) than those with the 34GA/AA genotypes. Furthermore, the DFS and OS were significantly diminished in bone marrow transplantation (BMT) patients with the 34GA/AA genotypes relative to those with the 34GG genotype. Conclusions These results suggest that these highly prevalent ABCG2 34GA/AA genotypes are associated with poor prognosis of Chinese patients with acute leukaemia and BMT patients.