次世代シーケンサ解析を含む遺伝学的検査の質と臨床的評価、倫理社会的問題の検討

2016 Fiscal Year Research-status Report

• Project/Area Number: 15K08646
• Research Institution: Kyoto University
• Principal Investigator: 小杉 眞司 京都大学, 医学研究科, 教授 (50252432)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 遺伝子検査学

Outline of Annual Research Achievements

がんのクリニカルシーケンスを約100例経験し、ACMG（American College of Medical Genetics and Genomics）が提唱している開示すべき偶発的所見=IF(Incidental Findings)あるいは二次的所見=SF(Secondary　Findings)に相当する遺伝子59に該当したものが、生殖細胞系列に同定・確認された場合に、遺伝カウンセリングを伴って開示を行う経験を得、データやケースの蓄積を行った。遺伝子診療の現場においてもNGS(Next Generation Sequencer)を用いた解析時に実際に発生するIF/SF事例に対して検討を行い、問題点を整理した。また、IF/SF取扱に関する世界的な状況の情報収集を継続的に行った。
消費者直販型遺伝子検査であるDTC（Direct-to-Consumer）genetic testingなどの遺伝子検査ビジネスにおける国内及び世界的な状況把握と問題点について情報収集を継続的に実施した。また、遺伝子検査ビジネスで行われる遺伝子検査及び臨床検査として実施される遺伝学的検査についての経験、考え方、今後の方針などを明らかにするために、一般診療を行っている開業医を中心とする医師会員を対象としたアンケート調査に実施し、現状把握に努めた。また、実際にDTCキットを購入して自ら検査を行い、結果データの比較や提供される情報について調査した。
従来型の単一遺伝性疾患の遺伝学的検査の臨床的な妥当性、有用性については、主に家族性腫瘍（Lynch症候群、家族性大腸ポリポーシス、多発性内分泌腫瘍症1型・2型、遺伝性乳がん卵巣がん症候群など）を中心に解析し、データを蓄積した。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

交付申請書に記載した目的が順調に達成できつつあるため。

Strategy for Future Research Activity

日本人におけるIF/SF開示における課題と問題点を抽出し、一定の方策の提言を目指す。日本人の遺伝医学専門家およびがん診療専門家に対して、IF/SF開示方針に関するアンケート調査を実施し、2013年のものとの比較をする。

Causes of Carryover

28年度はデータベース使用料以外の費用を節減することができたため、29年度の研究充実のために使用することができるようになった。

Expenditure Plan for Carryover Budget

本研究では、情報収集と整理が重要となるため、各種学会等での情報収集のための旅費・参加費および学内での作業を依頼する研究協力者に対する謝金が主体となる。その他、収集データの保存・活用のための電子媒体の購入費用、特定のデータベース使用料などにも研究費を使用する。

Research Products

• [Journal Article] Risks and Cough-Aggravating Factors in Prolonged Cough: Epidemiological Observations from the Nagahama Cohort Study. (2017)
  • Author(s): Matsumoto H, Izuhara Y, Niimi A, Tabara Y, Nagasaki T, Kanemitsu Y, Murase K, Oguma T, Ito I, Muro S, Sekine A, Matsuda F, Kosugi S, Nakayama T, Chin K, Mishima M; Nagahama Study Collaboration Group.
  • Journal Title: Ann Am Thorac Soc Volume: Feb 10 Pages: 記載なし
  • DOI: 10.1513/AnnalsATS.201608-616BC
  • Peer Reviewed
• [Journal Article] Combined association of clinical and lifestyle factors with non-restorative sleep: The Nagahama Study. (2017)
  • Author(s): Matsumoto T, Tabara Y, Murase K, Takahashi Y, Setoh K, Kawaguchi T, Muro S, Kadotani H, Kosugi S, Sekine A, Yamada R, Nakayama T, Mishima M, atsuda F, Chin K
  • Journal Title: PLoS One Volume: 12 Pages: e0171849
  • DOI: 10.1371/journal.pone.0171849
  • Peer Reviewed
• [Journal Article] Different inverse association of large high-density lipoprotein subclasses with exacerbation of insulin resistance and incidence of type 2 diabetes: The Nagahama study. (2017)
  • Author(s): Tabara Y, Arai H, Hirao Y, Takahashi Y, Setoh K, Kawaguchi T, Kosugi S, Ito Y, Nakayama T, Matsuda F; Nagahama study group.
  • Journal Title: Diabetes Res Clin Pract Volume: 127 Pages: 123-131
  • DOI: 10.1016/j.diabres.2017.03.018
  • Peer Reviewed
• [Journal Article] Relationship Among Chlamydia and Mycoplasma Pneumoniae Seropositivity, IKZF1 Genotype and Chronic Obstructive Pulmonary Disease in A General Japanese Population: The Nagahama Study. (2016)
  • Author(s): Muro S, Tabara Y, Matsumoto H, Setoh K, Kawaguchi T, Takahashi M, Ito I, Ito Y, Murase K, Terao C, Kosugi S, Yamada R, Sekine A, Nakayama T, Chin K, Mishima M, Matsuda F; Nagahama Study Group.
  • Journal Title: Medicine (Baltimore) Volume: 95 Pages: e3371
  • DOI: 10.1097/MD.0000000000003371
  • Peer Reviewed
• [Journal Article] Effects of atorvastatin on renal function in patients with dyslipidemia and chronic kidney disease: assessment of clinical usefulness in CKD patients with atorvastatin (ASUCA) trial. (2016)
  • Author(s): Kimura G, Kasahara M, Ueshima K, Tanaka S, Yasuno S, Fujimoto A, Sato T, Imamoto M, Kosugi S, Nakao K.
  • Journal Title: Clin Exp Nephrol. Volume: JUｌ Pages: 8
  • DOI: 10.1007/s10157-016-1304-6
  • Peer Reviewed
• [Journal Article] Mouth breathing, another risk factor for asthma: the Nagahama Study. (2016)
  • Author(s): Izuhara Y, Matsumoto H, Nagasaki T, Kanemitsu Y, Murase K, Ito I, Oguma T, Muro S, Asai K, Tabara Y, Takahashi K, Bessho K, Sekine A, Kosugi S, Yamada R, Nakayama T, Matsuda F, Niimi A, Chin K, Mishima M; Nagahama Study Group..
  • Journal Title: Allergy Volume: 71 Pages: 1031-1036
  • DOI: 10.1111/all.12885
  • Peer Reviewed
• [Journal Article] The causal effects of alcohol on lipoprotein subfraction and triglyceride levels using a Mendelian randomization analysis: The Nagahama study. (2016)
  • Author(s): Tabara Y, Arai H, Hirao Y, Takahashi Y, Setoh K, Kawaguchi T, Kosugi S, Ito Y, Nakayama T, Matsuda F; Nagahama study group.
  • Journal Title: Atherosclerosis. Volume: 257 Pages: 22-28
  • DOI: http://doi.org/10.1016/j.atherosclerosis.2016.12.008
  • Peer Reviewed
• [Presentation] Can learning family health history cause anxiety? (2016)
  • Author(s): Eriko Takamine, Yumie Hiraoka, Masako Torishima, Akira Inaba, Manami Matsukawa, Ayumi Yonei, Takahito Wada, Yasuharu Tabara, Fumihiko Matsuda, Shinji Kosugi
  • Organizer: Annual Meeting of American Society of Human Genetics
  • Place of Presentation: Vancouver
  • Year and Date: 2016-10-18 – 2016-10-22
  • Int'l Joint Research
• [Presentation] Views of patients and their parents regarding the incidental or secondary findings obtained from whole exome and genome sequencing: a literature review. (2016)
  • Author(s): Akira Inaba, Eriko Takamine, Manami Matsukawa, Ayumi Yonei, Shinji Kosugi.
  • Organizer: Annual Meeting of American Society of Human Genetics
  • Place of Presentation: Vancouver
  • Year and Date: 2016-10-18 – 2016-10-22
  • Int'l Joint Research
• [Presentation] The information and psychosocial support provided during decision-making by pregnant women who are incidentally diagnosed with fetal abnormalities in Japan; An online survey. (2016)
  • Author(s): Sayaka Honda, Hidehiko Miyake, Shinji Kosug.
  • Organizer: 20th International Conference on Prenatal Diagnosis and Therapy.
  • Place of Presentation: Berlin
  • Year and Date: 2016-07-10 – 2016-07-13
  • Int'l Joint Research
• [Presentation] Cross-sectional study to identify Japanese HBOC kindred at the maximum risk categories suitable for expedited genetic screening. (2016)
  • Author(s): Kokichi Sugano, Chikako Shimizu, Teruhiko Yoshida, Daisuke Aoki, Kenta Masuda, Kenjiro Kosaki, Kouji Tanakaya, Hiroshi Yagata, Mikiko Aoki, Shozo Ohsumi, Keika Kaneko, Shinji Kosugi, Tadashi Nomizu, Shinya Oda, Tomoki Koshou.
  • Organizer: The 6th Internationa Symposium of Hereditary Breast and Ovarian Cancer.
  • Place of Presentation: Montreal
  • Year and Date: 2016-05-10 – 2016-05-13
  • Int'l Joint Research
• [Presentation] The Current Landscape of the After-Sales Services of Direct-To-Consumer (DTC) Genetic Testing in Japan. (2016)
  • Author(s): Eriko Takamine, Hidehiko Miyake, Manami Matsukawa, Akira Inaba, Ayumi Yonei, Yumie Hiraoka, Sayaka Honda, Hitomi Nishio, Takahito Wada, Shinji Kosugi.
  • Organizer: The 13th Internationa Congress of Human Genetics.
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2016-04-03 – 2016-04-07
  • Int'l Joint Research
• [Presentation] Developing a MANGA cartoon medium that can promote Family Health History (2016)
  • Author(s): Yumie Hiraoka, Masako Torishima, Nana Akiyama, Takahito Wada, Shinji Kosugi.
  • Organizer: The 13th Internationa Congress of Human Genetics.
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2016-04-03 – 2016-04-07
  • Int'l Joint Research
• [Presentation] Views of Patients and Their Parents Regarding the Incidental or Secondary Findings Obtained from Whole Exome and Genome Sequencing: a Literature Review. (2016)
  • Author(s): Akira Inaba, Hitomi Nishio, Yumie Hiraoka, Sayaka Honda, Eriko Takamine, Manami Matsukawa, Ayumi Yonei,Shinji Kosugi.
  • Organizer: The 13th Internationa Congress of Human Genetics.
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2016-04-03 – 2016-04-07
  • Int'l Joint Research
• [Presentation] Characteristics of the Genetic Counseling in Kyoto University Hospital to Figure out the Genetic Counseling Needs in Japan. (2016)
  • Author(s): Manami Matsukawa, Hitomi Nishio, Yumie Hiraoka, Sayaka Honda, Akira Inaba, Eriko Takamine, Ayumi Yonei, Masako Torishima, Hiromi Murakami, Shin-ichiro Kitajiri, Takahito Wada, Hidehiko Miyake, Shigehito Yamada, Toshio Heike, Shinji Kosugi.
  • Organizer: The 13th Internationa Congress of Human Genetics.
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2016-04-03 – 2016-04-07
  • Int'l Joint Research
• [Presentation] Provided information and psychosocial support for decision-making process of pregnant women with incidental diagnosis of fetal abnormalities in Japan -Online based survey. (2016)
  • Author(s): Sayaka Honda, Hidehiko Miyake, Hitomi Nishio, YumieHiraoka, Shinji Kosugi.
  • Organizer: The 13th Internationa Congress of Human Genetics.
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2016-04-03 – 2016-04-07
  • Int'l Joint Research
• [Presentation] Evaluation of the management of incidental findings in next-generation sequencing: A questionnaire survey involving genetics professionals. (2016)
  • Author(s): Mio Tsuchiya, Shinji Kosugi.
  • Organizer: The 13th Internationa Congress of Human Genetics.
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2016-04-03 – 2016-04-07
  • Int'l Joint Research