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.
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.
Kwon
Woo Sun
WS
Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
Rha
Sun Young
SY
Jeung
Hei-Cheul
HC
Ahn
Joong Bae
JB
Jung
Jae Joon
JJ
Noh
Sung Hoon
SH
Chung
Hyun Cheol
HC
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
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