Identification of polymorphisms in drug-transporter genes associated with clinical outcome of adjuvant tamoxifen therapy for breast cancer patients

• Project/Area Number: 22790179
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: The University of Tokushima (2011); The Institute of Physical and Chemical Research (2010)
• Principal Investigator: KIYOTANI Kazuma 徳島大学, 疾患ゲノム研究センター, 助教 (30433642)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 遺伝子多型 / トランスポーター / タモキシフェン / 乳がん / GWAS / ゲノムワイド関連解析 / 個人差

Research Abstract

We screened novel genetic makers determining the efficacy of adjuvant tamoxifen therapy in breast cancer patients. We identified that single nucleotide polymorphisms in ABCC2/ MRP2 and C10orf11 showed significantly associated with the clinical outcomes of patients receiving adjuvant tamoxifen therapy. The number of risk alleles of these two genes and previously-identified maker, CYP2D6, had cumulative effects on recurrence-free survival among the breast cancer patients receiving tamoxifen monotherapy.

Research Products

• [Journal Article] The Malaysian NPC Study Group, Ching-Ching Ng. Identification of a functional variant in SPLUNC1 associated with nasopharyngeal carcinoma susceptibility among Malaysian Chinese (2012)
  • Author(s): Poh-Yin Yew, Taisei Mushiroda, Kazuma Kiyotani, Gopala Krishnan Govindasamy, Lee-Fah Yap, Soo-Hwang Teo, Paul Vey-Hong Lim, Selvaratnam Govindaraju, Kananathan Ratnavelu, Choon-Kook Sam, Yoke-Yeow Yap, Alan Soo-Beng Khoo, Kin-Choo Pua, Yusuke Nakamura
  • Journal Title: Mol Carcinog Volume: (in press) Issue: S1
  • DOI: 10.1002/mc.21857
  • Peer Reviewed
• [Journal Article] A genome-wide association study identifies four genetic markers for hematological toxicities in cancer patients receiving gemcitabine therapy (2012)
  • Author(s): Kazuma Kiyotani*, Satoko Uno*, Taisei Mushiroda, Atsushi Takahashi, Michiaki Kubo, Naoki Mitsuhata, Shinomi Ina, Chikashi Kihara, Yasutoshi Kimura, Hiroki Yamaue, Koichi Hirata, Yusuke Nakamura, Hitoshi Zembutsu
  • Journal Title: Pharmacogenet Genomics Volume: 22 Issue: 4 Pages: 229-235
  • DOI: 10.1097/fpc.0b013e32834e9eba
  • Peer Reviewed
• [Journal Article] Dose-adjustment study of tamoxifen based on CYP2D6 genotypes in Japanese breast cancer patients (2012)
  • Author(s): Kiyotani, K., et.al.
  • Journal Title: Breast Cancer Res Treat Volume: 131(1) Issue: 1 Pages: 137-45
  • DOI: 10.1007/s10549-011-1777-7
  • Peer Reviewed
• [Journal Article] CYP2B6 genotype is a strong predictor of systemic exposure to efavirenz in HIV-infected Zimbabweans (2012)
  • Author(s): Milimo Maimbo, Kazuma Kiyotani, Taisei Mushiroda, Collen Masimirembwa, Yusuke Nakamura
  • Journal Title: Eur J Clin Pharmacol Volume: 68 Issue: 3 Pages: 267-271
  • DOI: 10.1007/s00228-011-1118-0
  • Peer Reviewed
• [Journal Article] Pharmacogenomics of tamoxifen : roles of drug metabolizing enzymes and transporters (2012)
  • Author(s): Kiyotani K, et al
  • Journal Title: Drug Metab Pharmacokinet Volume: 28 Pages: 122-131
  • NAID: 130004463222
  • Peer Reviewed
• [Journal Article] A genome-wide association study identifies locus at 10q22 associated with clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients in Japanese (2011)
  • Author(s): K.Kiyotani, T.Mushiroda, T.Tsunoda, T.Morizono, N.Hosono, M.Kubo, Y.Tanigawara, CK.Imamura, DA.Flockhart, F.Aki, K.Hirata, Y.Takatsuka, M.Okazaki, S.Ohsumi, T.Yamakawa, M.Sasa, Y.Nakamura, H.Zembutsu
  • Journal Title: Human Molecular Genetics Volume: (オンライン出版済) Issue: 7 Pages: 1665-1672
  • DOI: 10.1093/hmg/ddr597
  • Peer Reviewed
• [Journal Article] Different effects of TERT, TP63, and CYP2A6 polymorphism on individual risk of tobacco-related lung cancer in male Japanese smokers (2011)
  • Author(s): Makiko Shimizu*, Kazuma Kiyotani*, Hideo Kunitoh, Tetsuya Kamataki, Hiroshi Yamazaki
  • Journal Title: J Cancer Ther Volume: 2 Issue: 05 Pages: 690-696
  • DOI: 10.4236/jct.2011.25093
  • Peer Reviewed
• [Journal Article] A functional variant in ZNF512B is associated with susceptibility to amyotrophic lateral sclerosis in Japanese. (2011)
  • Author(s): Iida A
  • Journal Title: Hum Mol Genet Volume: 20 Issue: 18 Pages: 3684-3692
  • DOI: 10.1093/hmg/ddr268
  • Peer Reviewed
• [Journal Article] Human cytochrome P450 1A1 is a novel target gene of liver X receptorα (2011)
  • Author(s): Norihito Shibahara, Yuiko Masunaga, Shunsuke Iwano, Hiroshi Yamazaki, Kazuma Kiyotani, Tetsuya Kamataki
  • Journal Title: Drug Metab Pharmacokinet Volume: 26 Pages: 451-457
  • Peer Reviewed
• [Journal Article] Human cytochrome P450 1A1 is a novel target gene of liver X receptor α (2011)
  • Author(s): Shibahara N, et al
  • Journal Title: Drug Metab Pharmacokinet Volume: 26 Pages: 451-457
  • Peer Reviewed
• [Journal Article] Development of new HLA-B* 3505 genotyping method using Invader assay (2010)
  • Author(s): Naoya Hosono, Soranun Chantarangsu, Kazuma Kiyotani, Sadaaki Takata, Yumiko Tsuchiya, Surakameth Mahasirimongkol, Wasun Chantratita, Taisei Mushiroda, Yusuke Nakamura, Michiaki Kubo
  • Journal Title: Pharmacogenet Genomics Volume: 20 Issue: 10 Pages: 630-633
  • DOI: 10.1097/fpc.0b013e32833ddc0a
  • Peer Reviewed
• [Journal Article] Limited effects of frequent CYP2D6* 36-* 10 tandem duplication allele on in vivo dextromethorphan metabolism in a Japanese population (2010)
  • Author(s): Kazuma Kiyotani, Makiko Shimizu, Toshio Kumai, Tetsuya Kamataki, Shinichi Kobayashi, Hiroshi Yamazaki
  • Journal Title: Eur J Clin Pharmacol Volume: 66 Issue: 10 Pages: 1065-1068
  • DOI: 10.1007/s00228-010-0876-4
  • Peer Reviewed
• [Journal Article] Biomonitoring of urinary cotinine concentrations associated with plasma levels of nicotine metabolites after daily cigarette smoking in a male Japanese population (2010)
  • Author(s): Taku Nagano, Makiko Shimizu, Kazuma Kiyotani, Tetsuya Kamataki, Ryohji Takano, Norie Murayama, Fumiaki Shono, Hiroshi Yamazaki
  • Journal Title: Int J Environ Res Public Healthi Volume: 7 Issue: 7 Pages: 2953-2964
  • DOI: 10.3390/ijerph7072953
  • Peer Reviewed
• [Journal Article] Lessons for pharmacogenomics studies : association study between CYP2D6 genotype and tamoxifen response (2010)
  • Author(s): Kazuma Kiyotani, Taisei Mushiroda, Naoya Hosono, Tatsuhiko Tsunoda, Michiaki Kubo, Fuminori Aki, Okazaki Yutaka, Koichi Hirata, Yuichi Takatsuka, Minoru Okazaki, Shozo Ohsumi, Takashi Yamakawa, Mitsunori Sasa, Yusuke Nakamura, Hitoshi Zembutsu
  • Journal Title: Pharmacogenet Genomics Volume: 20 Issue: 9 Pages: 565-568
  • DOI: 10.1097/fpc.0b013e32833af231
  • Peer Reviewed
• [Journal Article] Lessons for pharmacogenomics studies : association study between CYP2D6 genotype and tamoxifen response. (2010)
  • Author(s): Kiyotani K, et al
  • Journal Title: Pharmacogenet Genomics Volume: 20 Pages: 565-568
  • Peer Reviewed
• [Journal Article] Development of new HLA-B^*3505 genotyping method using Invader assay. (2010)
  • Author(s): Hosono N, et al
  • Journal Title: Pharmacogenet Genomics Volume: 20 Pages: 630-603
  • Peer Reviewed
• [Journal Article] Limited effects of frequent CYP2D6^*36-^*10 tandem duplication allele on in vivo dextromethorphan metabolism in a Japanese population. (2010)
  • Author(s): Kiyotani K, et al
  • Journal Title: Int J Environ Res Public Health Volume: 7 Pages: 1065-1068
  • Peer Reviewed
• [Journal Article] Biomonitoring of urinary cotinine concentrations associated with plasma levels of nicotine metabolites after daily cigarette smoking in a male Japanese population. (2010)
  • Author(s): Nagano T, et al
  • Journal Title: Eur J Clin Pharmacol Volume: 66 Pages: 2953-2964
  • Peer Reviewed
• [Presentation] タモキシフェンの乳がん再発予防効果に及ぼすCYP2D6およびABCC2遺伝子多型の影響 (2010)
  • Author(s): 清谷一馬, 莚田泰誠, 今村知世, 細野直哉, 角田達彦, 久保充明, 谷川原祐介, 平田公一, 大住省三, 笹三徳, 中村祐輔, 前佛均
  • Organizer: 第31回日本臨床薬理学会年会
  • Place of Presentation: 京都(国立京都国際会館)
  • Year and Date: 2010-12-03
• [Presentation] タモキシフェンの乳がん再発予防効果に及ぼすCYP2D6およびABCC2遺伝子多型の影響 (2010)
  • Author(s): 清谷一馬, ら
  • Organizer: 第31回 日本臨床薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2010-12-03
• [Presentation] Association between polymorphisms in CYP2D6 and ABCC2 and clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients (2010)
  • Author(s): Kazuma Kiyotani, Taisei Mushiroda, Chiyo K. Imamura, Naoya Hosono, Tatsuhiko Tsunoda, Michiaki Kubo, Yusuke Tanigawara, Fuminori Aki, Koichi Hirata, Yuichi Takatsuka, Minoru Okazaki, Shozo Ohsumi, Takashi Yamakawa, Mitsunori Sasa, Yusuke Nakamura, Hitoshi Zembutsu
  • Organizer: The American Society of Human Genetics 60th Annual Meeting(ASHG2010)
  • Place of Presentation: Washington DC
  • Year and Date: 2010-11-03
• [Presentation] Association between polymorphisms in CYP2D6 and ABCC2 and clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients. (2010)
  • Author(s): Kiyotani K, et al
  • Organizer: American Society of Human Genetics 60th Annual Meeting (ASHG2010)
  • Place of Presentation: Washington DC
  • Year and Date: 2010-11-03
• [Presentation] タモキシフェンの乳がん再発予防効果に関連する薬物トランスポーターの遺伝子多型 (2010)
  • Author(s): 清谷一馬, 莚田泰誠, 今村知世, 細野直哉, 角田達彦, 久保充明, 谷川原祐介, 安藝史典, 平田公一, 高塚雄一, 岡崎稔, 大住省三, 山川卓, 笹三徳, 中村祐輔, 前佛均
  • Organizer: 日本人類遺伝学会第55回大会
  • Place of Presentation: 大宮(大宮ソニックシティ)
  • Year and Date: 2010-10-28
• [Presentation] タモキシフェンの乳がん再発予防効果に関連する薬物トランスポーターの遺伝子多型 (2010)
  • Author(s): 清谷一馬, ら
  • Organizer: 日本人類遺伝学会第55回大会
  • Place of Presentation: 大宮
  • Year and Date: 2010-10-28
• [Presentation] Effects of polymorphisms in CYP2D6 and ABCC2 on clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients (2010)
  • Author(s): Kazuma Kiyotani, Taisei Mushiroda, Chiyo K. Imamura, Naoya Hosono, Tatsuhiko Tsunoda, Michiaki Kubo, Yusuke Tanigawara, Fuminori Aki, Koichi Hirata, Yuichi Takatsuka, Minoru Okazaki, Shozo Ohsumi, Takashi Yamakawa, Mitsunori Sasa, Yusuke Nakamura, Hitoshi Zembutsu
  • Organizer: 日本薬物動態学会第25回年会(東京)
  • Place of Presentation: 大宮(大宮ソニックシティ)
  • Year and Date: 2010-10-08
• [Presentation] Effects of polymorphisms in CYP2D6 and ABCC2 on clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients. (2010)
  • Author(s): Kiyotani K, et al
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: 東京
  • Year and Date: 2010-10-08