Abstract 759: ATP-binding cassette (ABC) genes genotype and expression: A potential association with pancreatic cancer development and chemoresistance

Abstract

Abstract Genetic polymorphisms in ATP-Binding Cassette (ABC) transporter genes are associated with different responses to chemotherapy in various cancers including pancreatic cancer. In this study, four single nucleotide polymorphisms (SNPs) in the ABCB1, ABCC1 and ABCG2 genes were investigated in normal and pancreatic cancer specimens. The potential association with expression of the efflux pumps was also analyzed. The TT genotypes of G2677T and C3435T in ABCB1 gene were associated with lower risk of developing pancreatic cancer in the investigated populations (p=0.013, OR=0.35 and p=0.015, OR=0.29, respectively). To our knowledge, this is the first report of the common polymorphisms in ABCB1 gene affecting the genetic risk of developing pancreatic cancer. Moreover, compared to ABCB1 G2677T and C3435T wild-type homozygotes and heterozygotes, the expression of ABCB1 in mutant-type homozygotes (2677TT and 3435TT) was lower in normal pancreatic tissue (64.3% and 68.9%, respectively, p<0.05), and the same trend was also found in pancreatic cancer specimens. Interestingly, the pancreatic cancer cells MIA1, BXPC3 and CFPAC1 are ABCB1 2677TT-3435TT homozygotes. Cell viability assay revealed that these three cell lines were much more sensitive to gemcitabine than PANC1, SU86.86, PL-45, and ASPC1, which are either ABCB1 G2677T-C3435T wild type homozygotes or heterozygotes. These results are consistent with the clinical observation that for patients receiving post-operative gemcitabine chemotherapy, the overall survival is tended to be longer in the ABCB1 2677TT and 3435TT carriers. Conclusion: Polymorphisms in ABCB1 G2677T and G3435T were associated with different susceptibility to pancreatic cancer and may predict responses to chemotherapy. Citation Format: Li Pang, Beverly Word, Joshua Xu, George Hammons, Shiew-Mei Huang, Beverly Lyn-Cook. ATP-binding cassette (ABC) genes genotype and expression: A potential association with pancreatic cancer development and chemoresistance. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 759. doi:10.1158/1538-7445.AM2014-759