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Pharmacogenomics J. 2018 Sep;18(5):633-645. doi: 10.1038/s41397-018-0016-6. Epub 2018 Apr 4.

Associations between genetic polymorphisms of membrane transporter genes and prognosis after chemotherapy: meta-analysis and finding from Seoul Breast Cancer Study (SEBCS).

Kim JE1, Choi J1, Park J1, Park C1, Lee SM2, Park SE3, Song N4, Chung S5, Sung H6, Han W4,7, Lee JW8, Park SK1,4,9, Kim MK10, Noh DY4,7, Yoo KY9,11, Kang D1,4,9,12, Choi JY13,14,15.

Author information

1
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
2
College of Pharmacy Chonnam National University, Gwangju, Korea.
3
College of Pharmacy, Duksung Women's university, Seoul, Korea.
4
Cancer Research Institute, Seoul National University, Seoul, Korea.
5
Division for New Health Technology Assessment, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea.
6
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
7
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
8
Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
9
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
10
Division of Cancer Epidemiology and Management, National Cancer Center, Goyang, Korea.
11
The Armed Forces Capital Hospital, Seongnam, Korea.
12
Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Korea.
13
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea. jiyeob.choi@gmail.com.
14
Cancer Research Institute, Seoul National University, Seoul, Korea. jiyeob.choi@gmail.com.
15
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea. jiyeob.choi@gmail.com.

Abstract

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 (Pgene < 0.05). ABCB1 rs1202172 was differentially associated with survival depending on the chemotherapy (Pinteraction = 0.035). Our finding provides suggestive associations of membrane transporters on cancer survival.

PMID:
29618765
DOI:
10.1038/s41397-018-0016-6
[Indexed for MEDLINE]

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