Kim Ji-Eun, Choi Jaesung, Park JooYong, Park Chulbum, Lee Se Mi, Park Seong Eun, Song Nan, Chung Seokang, Sung Hyuna, Han Wonshik, Lee Jong Won, Park Sue K, Kim Mi Kyung, Noh Dong-Young, Yoo Keun-Young, Kang Daehee, Choi Ji-Yeob
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
College of Pharmacy Chonnam National University, Gwangju, Korea.
Pharmacogenomics J. 2018 Sep;18(5):633-645. doi: 10.1038/s41397-018-0016-6. Epub 2018 Apr 4.
Membrane transporters can be major determinants of the pharmacokinetic profiles of anticancer drugs. The associations between genetic variations of ATP-binding cassette (ABC) and solute carrier (SLC) genes and cancer survival were investigated through a meta-analysis and an association study in the Seoul Breast Cancer Study (SEBCS). Including the SEBCS, the meta-analysis was conducted among 38 studies of genetic variations of transporters on various cancer survivors. The population of SEBCS consisted of 1338 breast cancer patients who had been treated with adjuvant chemotherapy. A total of 7750 SNPs were selected from 453 ABC and/or SLC genes typed by an Affymetrix 6.0 chip. ABCB1 rs1045642 was associated with poor progression-free survival in a meta-analysis (HR = 1.33, 95% CI: 1.07-1.64). ABCB1, SLC8A1, and SLC12A8 were associated with breast cancer survival in SEBCS (P < 0.05). ABCB1 rs1202172 was differentially associated with survival depending on the chemotherapy (P = 0.035). Our finding provides suggestive associations of membrane transporters on cancer survival.
膜转运蛋白可能是抗癌药物药代动力学特征的主要决定因素。通过荟萃分析和首尔乳腺癌研究（SEBCS）中的关联研究，探讨了ATP结合盒（ABC）和溶质载体（SLC）基因的遗传变异与癌症生存率之间的关联。包括SEBCS在内，对38项关于各种癌症幸存者转运蛋白遗传变异的研究进行了荟萃分析。SEBCS的研究对象包括1338例接受辅助化疗的乳腺癌患者。通过Affymetrix 6.0芯片对453个ABC和/或SLC基因进行分型，共选择了7750个单核苷酸多态性（SNP）。在荟萃分析中，ABCB1 rs1045642与无进展生存期较差相关（风险比[HR]=1.33，95%置信区间[CI]：1.07-1.64）。在SEBCS中，ABCB1、SLC8A1和SLC12A8与乳腺癌生存率相关（P<0.05）。ABCB1 rs1202172根据化疗情况与生存率存在差异关联（P=0.035）。我们的研究结果提示了膜转运蛋白与癌症生存率之间的关联。
