Genetic variation in the ATP binding cassette transporter ABCC10 is associated with neutropenia for docetaxel in Japanese lung cancer patients cohort
Abstract Background Docetaxel is a widely used cytotoxic agent for treatments of various cancers. The ATP binding cassette (ABC) transporter / multidrug resistance protein (MRP) ABCC10/MRP7, involved in transporting taxanes, has been associated with resistance to these agents. Since genetic variatio...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-019-5438-2 |
| _version_ | 1818062159616147456 |
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| author | Kazuki Sone Tetsuya Oguri Takehiro Uemura Akira Takeuchi Satoshi Fukuda Osamu Takakuwa Ken Maeno Kensuke Fukumitsu Yoshihiro Kanemitsu Hirotsugu Ohkubo Masaya Takemura Yutaka Ito Akio Niimi |
| author_facet | Kazuki Sone Tetsuya Oguri Takehiro Uemura Akira Takeuchi Satoshi Fukuda Osamu Takakuwa Ken Maeno Kensuke Fukumitsu Yoshihiro Kanemitsu Hirotsugu Ohkubo Masaya Takemura Yutaka Ito Akio Niimi |
| author_sort | Kazuki Sone |
| collection | DOAJ |
| description | Abstract Background Docetaxel is a widely used cytotoxic agent for treatments of various cancers. The ATP binding cassette (ABC) transporter / multidrug resistance protein (MRP) ABCC10/MRP7, involved in transporting taxanes, has been associated with resistance to these agents. Since genetic variation in drug transporters may affect clinical outcomes, we examined whether polymorphism of ABCC10 could affect clinical responses to docetaxel. Methods Using 18 NSCLC cell lines and CRISPR-based genome-edited HeLa cells, we analyzed whether genetic variants of ABCC10 (rs2125739, rs9349256) affected cytotoxicity to docetaxel. Subsequently, we analyzed genetic variants [ABCC10 (rs2125739), ABCB1 (C1236T, C3435T, G2677 T/A), ABCC2 (rs12762549), and SLCO1B3 (rs11045585)] in 69 blood samples of NSCLC patients treated with docetaxel monotherapy. Clinical outcomes were evaluated between genotype groups. Results In the cell lines, only one genetic variant (rs2125739) was significantly associated with docetaxel cytotoxicity, and this was confirmed in the genome-edited cell line. In the 69 NSCLC patients, there were no significant differences related to rs2125739 genotype in terms of RR, PFS, or OS. However, this SNP was associated with grade 3/4 neutropenia (T/C group 60% vs. T/T group 87%; P = 0.028). Furthermore, no patient with a T/C genotype experienced febrile neutropenia. Conclusions Our results indicate that genetic variation in the ABCC10 gene is associated with neutropenia for docetaxel treatment. |
| first_indexed | 2024-12-10T13:59:47Z |
| format | Article |
| id | doaj.art-9db115492e1b43d0a3d1002f6aa7b2bc |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-10T13:59:47Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-9db115492e1b43d0a3d1002f6aa7b2bc2022-12-22T01:45:50ZengBMCBMC Cancer1471-24072019-03-011911910.1186/s12885-019-5438-2Genetic variation in the ATP binding cassette transporter ABCC10 is associated with neutropenia for docetaxel in Japanese lung cancer patients cohortKazuki Sone0Tetsuya Oguri1Takehiro Uemura2Akira Takeuchi3Satoshi Fukuda4Osamu Takakuwa5Ken Maeno6Kensuke Fukumitsu7Yoshihiro Kanemitsu8Hirotsugu Ohkubo9Masaya Takemura10Yutaka Ito11Akio Niimi12Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical SciencesDepartment of Education and Research Center for Community Medicine, Nagoya City University Graduate School of Medical SciencesDepartment of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical SciencesDepartment of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical SciencesDepartment of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical SciencesDepartment of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical SciencesDepartment of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical SciencesDepartment of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical SciencesDepartment of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical SciencesDepartment of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical SciencesDepartment of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical SciencesDepartment of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical SciencesDepartment of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical SciencesAbstract Background Docetaxel is a widely used cytotoxic agent for treatments of various cancers. The ATP binding cassette (ABC) transporter / multidrug resistance protein (MRP) ABCC10/MRP7, involved in transporting taxanes, has been associated with resistance to these agents. Since genetic variation in drug transporters may affect clinical outcomes, we examined whether polymorphism of ABCC10 could affect clinical responses to docetaxel. Methods Using 18 NSCLC cell lines and CRISPR-based genome-edited HeLa cells, we analyzed whether genetic variants of ABCC10 (rs2125739, rs9349256) affected cytotoxicity to docetaxel. Subsequently, we analyzed genetic variants [ABCC10 (rs2125739), ABCB1 (C1236T, C3435T, G2677 T/A), ABCC2 (rs12762549), and SLCO1B3 (rs11045585)] in 69 blood samples of NSCLC patients treated with docetaxel monotherapy. Clinical outcomes were evaluated between genotype groups. Results In the cell lines, only one genetic variant (rs2125739) was significantly associated with docetaxel cytotoxicity, and this was confirmed in the genome-edited cell line. In the 69 NSCLC patients, there were no significant differences related to rs2125739 genotype in terms of RR, PFS, or OS. However, this SNP was associated with grade 3/4 neutropenia (T/C group 60% vs. T/T group 87%; P = 0.028). Furthermore, no patient with a T/C genotype experienced febrile neutropenia. Conclusions Our results indicate that genetic variation in the ABCC10 gene is associated with neutropenia for docetaxel treatment.http://link.springer.com/article/10.1186/s12885-019-5438-2ABC transporterSingle nucleotide polymorphismDocetaxelNeutropenia |
| spellingShingle | Kazuki Sone Tetsuya Oguri Takehiro Uemura Akira Takeuchi Satoshi Fukuda Osamu Takakuwa Ken Maeno Kensuke Fukumitsu Yoshihiro Kanemitsu Hirotsugu Ohkubo Masaya Takemura Yutaka Ito Akio Niimi Genetic variation in the ATP binding cassette transporter ABCC10 is associated with neutropenia for docetaxel in Japanese lung cancer patients cohort BMC Cancer ABC transporter Single nucleotide polymorphism Docetaxel Neutropenia |
| title | Genetic variation in the ATP binding cassette transporter ABCC10 is associated with neutropenia for docetaxel in Japanese lung cancer patients cohort |
| title_full | Genetic variation in the ATP binding cassette transporter ABCC10 is associated with neutropenia for docetaxel in Japanese lung cancer patients cohort |
| title_fullStr | Genetic variation in the ATP binding cassette transporter ABCC10 is associated with neutropenia for docetaxel in Japanese lung cancer patients cohort |
| title_full_unstemmed | Genetic variation in the ATP binding cassette transporter ABCC10 is associated with neutropenia for docetaxel in Japanese lung cancer patients cohort |
| title_short | Genetic variation in the ATP binding cassette transporter ABCC10 is associated with neutropenia for docetaxel in Japanese lung cancer patients cohort |
| title_sort | genetic variation in the atp binding cassette transporter abcc10 is associated with neutropenia for docetaxel in japanese lung cancer patients cohort |
| topic | ABC transporter Single nucleotide polymorphism Docetaxel Neutropenia |
| url | http://link.springer.com/article/10.1186/s12885-019-5438-2 |
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