title: G-T haplotype (2677G>T/A and 3435C>T) of ABCB1 gene polymorphisms is associated with ethnic differences to paclitaxel sensitivity in cancer cells with different gene expression pattern.
abstract: At 2677, the GG and TT were most frequent in Asian cell lines, whereas the GT and GG were most frequent in non-Asians (p=0.032). At 3435, TT and CC was most common in Asians and non-Asians, respectively (p=0.018). A higher IC(50) was found in GG than GT/A genotype (p=0.02) and in G-C than G-T haplotype (p=0.046). Non-Asian cell lines were more sensitive to paclitaxel than Asian cell lines (p=0.01) due to different polymorphism frequencies. We identified 65 genes that were differently expressed in cell lines of the G-C and G-T ABCB1 haplotypes. Ethnic differences in the G-T haplotype of the ABCB1 gene may be a biomarker for paclitaxel sensitivity, and future clinical validation is necessary to confirm our findings.
authors.affiliation: Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Woo Sun
authors.initials: WS
authors.lastname: Kwon
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Hei-Cheul
authors.initials: HC
authors.lastname: Jeung
authors.forename: Joong Bae
authors.initials: JB
authors.lastname: Ahn
authors.forename: Jae Joon
authors.initials: JJ
authors.lastname: Jung
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Noh
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D044466:Asian People; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D006239:Haplotypes; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel