A cohort-study on the association of intensity-spcific physical activity with DNA methylation in peripheral blood and risk of colon and breast cancers

• Project/Area Number: 17H01554
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Epidemiology and preventive medicine
• Research Institution: Saga University
• Principal Investigator: Tanaka Keitaro 佐賀大学, 医学部, 教授 (50217022)
• Co-Investigator(Kenkyū-buntansha): 原 めぐみ 佐賀大学, 医学部, 准教授 (90336115) ; 西田 裕一郎 佐賀大学, 医学部, 講師 (50530185) ; 大桃 秀樹 岩手医科大学, いわて東北メディカル・メガバンク機構, 特命講師 (90453406) ; 島ノ江 千里 佐賀大学, 医学部, 特任准教授 (10734064)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥42,770,000 (Direct Cost: ¥32,900,000、Indirect Cost: ¥9,870,000); Fiscal Year 2019: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000); Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2017: ¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000)
• Keywords: DNAメチル化 / 身体活動 / 結腸癌 / 乳癌 / コホート研究 / 末梢血DNAメチル化 / DNAメチル化解析

Outline of Final Research Achievements

We conducted an epigenome-wide association study (EWAS) on accelerometer-determined physical activity (PA) and DNA methylation in peripheral blood (about 440 thousand CpG sites), based on a cohort study of around 12 thousand residents in Saga city. We also evaluated the association between PA and colon/breast cancers and if DNA methylation mediates this possible association. In EWAS, we found a significant positive association of PA with cg07030336 (VTI1A/ZDHHC6 gene), which showed a variety of correlations with serum CRP and cytokines. We identified no significant association between PA and colon cancer but a significant inverse association between breast cancer and high-intensity PA (6 METs or more). However, cg07030336 was not associated with either cancer, suggesting the absence of mediation by this methylation in causation of either cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義としては、加速度計で客観的に測定された身体活動と関連する末梢血DNAメチル化としてcg07030336（VTI1A;ZDHHC6遺伝子）を初めて同定した点である。このメチル化は血中炎症マーカーと多彩な相関を示し（CRP、IL-4、IL-5などと負の相関、IL-6、IL-8、IL-15などと正の相関）、今回結腸癌・乳癌との関連は同定できなかったが、他の炎症性疾患との関連に介在する可能性がある。社会的意義としては、高強度身体活動（6メッツ以上）と乳癌の間に予防的関連が観察された事が挙げられ、現在わが国で女性にもっとも多い乳癌の予防の観点から重要な知見が得られた。

Research Products

• [Journal Article] Differential Effect of Polymorphisms on Body Mass Index Across the Life Course of Japanese: The Japan Multi-Institutional Collaborative Cohort Study (2021)
  • Author(s): Iwase M, Matsuo K, Nakatochi M, Oze I, Ito H, Koyanagi Y, et al
  • Journal Title: Journal of Epidemiology Volume: 31 Issue: 3 Pages: 172-179
  • DOI: 10.2188/jea.JE20190296
  • NAID: 130007995132
  • ISSN: 0917-5040, 1349-9092
  • Year and Date: 2021-03-05
  • Peer Reviewed / Open Access
• [Journal Article] Combined effect of weight gain within normal weight range and parental hypertension on the prevalence of hypertension; from the J-MICC Study. (2020)
  • Author(s): Okada R, Kadomatsu Y, Tsukamoto M, Sasakabe T, Kawai S, Tamura T, Hishida A, Ikezaki H, Furusyo N, Tanaka K, Hara M, Suzuki S, Watanabe M, Takezaki T, Nishimoto D, Matsui D, Watanabe I, Kuriki K, Takashima N, Nakamura Y, Katsuura-Kamano S, Arisawa K, Mikami H, Nakamura Y, Oze I, Koyanagi YN, Naito M, Wakai K
  • Journal Title: J. Hum. Hypertens. Volume: 34 Issue: 2 Pages: 125-131
  • DOI: 10.1038/s41371-019-0230-y
  • Peer Reviewed
• [Journal Article] Case-Control Study of Rotavirus Vaccine Effectiveness Compared to Test-Negative Controls or Hospital Controls (2019)
  • Author(s): Araki K, Hara M, Shimanoe C, Nishida Y, Matsuo M, Tanaka K
  • Journal Title: Journal of Epidemiology Volume: 29 Issue: 8 Pages: 282-287
  • DOI: 10.2188/jea.JE20180054
  • NAID: 130007687586
  • ISSN: 0917-5040, 1349-9092
  • Year and Date: 2019-08-05
  • Peer Reviewed / Open Access
• [Journal Article] Coffee consumption and mortality in Japanese men and women: A pooled analysis of eight population-based cohort studies in Japan (Japan Cohort Consortium). (2019)
  • Author(s): Abe SK, Saito E, Sawada N, Tsugane S, Ito H, Lin Y, Tamakoshi A, Sado J, Kitamura Y, Sugawara Y, Tsuji I, Nagata C, Sadakane A, Shimazu T, Mizoue T, Matsuo K, Naito M, Tanaka K, Inoue M
  • Journal Title: Prev. Med. Volume: 123 Pages: 270-277
  • DOI: 10.1016/j.ypmed.2019.04.002
  • Peer Reviewed / Open Access
• [Journal Article] Green tea consumption and mortality in Japanese men and women: a pooled analysis of eight population-based cohort studies in Japan. (2019)
  • Author(s): Abe SK, Saito E, Sawada N, Tsugane S, Ito H, Lin Y, Tamakoshi A, Sado J, Kitamura Y, Sugawara Y, Tsuji I, Nagata C, Sadakane A, Shimazu T, Mizoue T, Matsuo K, Naito M, Tanaka K, Inoue M
  • Journal Title: Eur. J. Epidemiol. Volume: 34 Issue: 10 Pages: 917-926
  • DOI: 10.1007/s10654-019-00545-y
  • Peer Reviewed / Open Access
• [Journal Article] Association of genetic risk score and chronic kidney disease in a Japanese population (2019)
  • Author(s): Fujii R, Hishida A, Nakatochi M, Furusyo N, Murata M, Tanaka K, Shimanoe C, Suzuki S, Watanabe M, Kuriyama N, Koyama T, Takezaki T, Shimoshikiryo I, Arisawa K, Katsuura-Kamano S, Takashima N, Turin TC, Kuriki K, Endoh K, Mikami H, Nakamura Y, Oze I, Ito H, Kubo M, Momozawa Y, Kondo T, Naito M, Wakai K
  • Journal Title: Nephrology Volume: 印刷中 Issue: 6 Pages: 670-673
  • DOI: 10.1111/nep.13479
  • Peer Reviewed
• [Journal Article] Associations of nutrient patterns with the prevalence of metabolic syndrome: Results from the baseline data of the Japan Multi-Institutional Collaborative Cohort Study. (2019)
  • Author(s): Yuki Iwasaki, Kokichi Arisawa, Sakurako Katsuura-Kamano, Hirokazu Uemura, Mineko Tsukamoto, Yuka Kadomatsu, Rieko Okada, Asahi Hishida, Keitaro Tanaka, Megumi Hara, Toshiro Takezaki
  • Journal Title: Nutrients Volume: 30 Issue: 5 Pages: 990-990
  • DOI: 10.3390/nu11050990
  • NAID: 120007097694
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout (2019)
  • Author(s): Kawamura Y, Nakaoka H, Nakayama A, et al.
  • Journal Title: Ann Rheum Dis Volume: 78 Issue: 10 Pages: 1430-1437
  • DOI: 10.1136/annrheumdis-2019-215521
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Smoking and Pancreatic Cancer Incidence: A Pooled Analysis of 10 Population-Based Cohort Studies in Japan (2019)
  • Author(s): Koyanagi Yuriko N.、Ito Hidemi、Matsuo Keitaro、Sugawara Yumi、Hidaka Akihisa、Sawada Norie、Wada Keiko、Nagata Chisato、Tamakoshi Akiko、Lin Yingsong、Takeuchi Taro、Kitamura Yuri、Utada Mai、Sadakane Atsuko、Mizoue Tetsuya、Naito Mariko、Tanaka Keitaro、Shimazu Taichi、Tsugane Shoichiro、Inoue Manami
  • Journal Title: Cancer Epidemiology Biomarkers & Prevention Volume: 28 Issue: 8 Pages: 1370-1378
  • DOI: 10.1158/1055-9965.epi-18-1327
  • Peer Reviewed / Open Access
• [Journal Article] Habitual Light-intensity Physical Activity and ASC Methylation in a Middle-aged Population (2019)
  • Author(s): Nishida Y、Hara M、Higaki Y、Taguchi N、Nakamura K、Nanri H、Horita M、Shimanoe C、Yasukata J、Miyoshi N、Yamada Y、Higashimoto K、Soejima H、Tanaka K
  • Journal Title: International Journal of Sports Medicine Volume: 40 Issue: 10 Pages: 670-677
  • DOI: 10.1055/a-0965-1374
  • Peer Reviewed
• [Journal Article] Revisit of an unanswered question by pooled analysis of eight cohort studies in Japan: Does cigarette smoking and alcohol drinking have interaction for the risk of esophageal cancer? (2019)
  • Author(s): Oze Isao、Charvat Hadrien、Matsuo Keitaro、Ito Hidemi、Tamakoshi Akiko、Nagata Chisato、Wada Keiko、Sugawara Yumi、Sawada Norie、Yamaji Taiki、Naito Mariko、Tanaka Keitaro、Shimazu Taichi、Mizoue Tetsuya、Tsugane Shoichiro、Inoue Manami
  • Journal Title: Cancer Medicine Volume: 8 Issue: 14 Pages: 6414-6425
  • DOI: 10.1002/cam4.2514
  • Peer Reviewed / Open Access
• [Journal Article] Coffee, green tea and liver cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. (2019)
  • Author(s): Tanaka K, Tamakoshi A, Sugawara Y, Mizoue T, Inoue M, Sawada N, Matsuo K, Ito H, Naito M, Nagata C, Kitamura Y, Sadakane A, Tsugane S, Shimazu T
  • Journal Title: Jpn. J. Clin. Oncol. Volume: 49 Issue: 10 Pages: 972-984
  • DOI: 10.1093/jjco/hyz097
  • Peer Reviewed
• [Journal Article] The interaction between ABCA1 polymorphism and physical activity on the HDL-cholesterol levels in a Japanese population (2019)
  • Author(s): Nishida Yuichiro、Hachiya Tsuyoshi、Hishida Asahi、Tsukamoto Mineko、Kadomatsu Yuka、Oze Isao、Koyanagi Yuriko N.、Kuriyama Nagato、Koyama Teruhide、Furusyo Norihiro、Suzuki Sadao、Nakagawa-Senda Hiroko, Naito Mariko、Wakai Kenji、for the Japan Multi-Institutional Collaborative Cohort Study Group, et al.
  • Journal Title: Journal of Lipid Research Volume: 61 Issue: 1 Pages: 86-94
  • DOI: 10.1194/jlr.p091546
  • Peer Reviewed / Open Access
• [Journal Article] Fish intake and risk of mortality due to aortic dissection and aneurysm : A pooled analysis of the Japan cohort consortium (2018)
  • Author(s): Yamagishi K, Iso H, Shimazu T, Tamakoshi A, Sawada N, Matsuo K, Ito H, Wakai K, Nakayama T, Kitamura Y, Sado J, Tsuji I, Sugawara Y, Mizoue T, Inoue M, Nagata C, Sadakane A, Tanaka K, Tsugane S, Sasazuki S
  • Journal Title: Clin Nutr Volume: 38 Issue: 4 Pages: 1678-1683
  • DOI: 10.1016/j.clnu.2018.08.007
  • NAID: 120007133478
  • Peer Reviewed / Open Access
• [Journal Article] Perceived stress, depressive symptoms, and oxidative DNA damage (2018)
  • Author(s): Shimanoe C, Hara M, Nishida Y, Nanri, H, Horita M, Yamada Y, Li YS, Kasai H, Kawai K, Higaki Y, Tanaka K
  • Journal Title: Psychosomatic Medicine Volume: 80 Issue: 1 Pages: 28-33
  • DOI: 10.1097/psy.0000000000000513
  • Peer Reviewed / Open Access
• [Journal Article] Coping strategy and social support modify the association between perceived stress and C-reactive protein: a longitudinal study of healthy men and women (2018)
  • Author(s): Shimanoe C, Hara M, Nishida Y, Nanri H, Otsuka Y, Horita M, Yasukata J, Miyoshi N, Yamada Y, Higaki Y, Tanaka K
  • Journal Title: Stress Volume: 21 Issue: 3 Pages: 237-246
  • DOI: 10.1080/10253890.2018.1435638
  • Peer Reviewed
• [Journal Article] Genomewide Association Study of Leisure-Time Exercise Behavior in Japanese Adults (2018)
  • Author(s): Hara M, Tachiya T, Sutodh T, et al
  • Journal Title: Medicine & Science in Sports & Exercise Volume: 50 Issue: 12 Pages: 2433-2441
  • DOI: 10.1249/mss.0000000000001712
  • Peer Reviewed / Open Access
• [Journal Article] Association of exposure level to passive smoking with hypertension among lifetime nonsmokers in Japan (2018)
  • Author(s): Tamura T, Kadomatsu Y, Tsukamoto M, Okada R, Sasakabe T, Kawai S, Hishida A, Hara M, Tanaka K, Shimoshikiryo I, Takezaki T, Watanabe I, Matsui D, Nishiyama T, Suzuki S, Endoh K, Kuriki K, Kita Y, Katsuura-Kamano S, Arisawa K, Ikezaki H, Furusyo N, Koyanagi YN, Oze I, Nakamura Y, Mikami H, Naito M, Wakai K
  • Journal Title: Medicine Volume: 97 Issue: 48 Pages: e13241-e13241
  • DOI: 10.1097/md.0000000000013241
  • Peer Reviewed / Open Access
• [Journal Article] A genome-wide association study of coping behaviors suggests FBXO45 is associated with emotional expression (2018)
  • Author(s): Shimanoe C, Hachiya T, Hara M, Nishida Y, Tanaka K, Sutoh Y, Shimizu A, et al
  • Journal Title: Genes, Brain and Behavior Volume: 印刷中 Issue: 2
  • DOI: 10.1111/gbb.12481
  • Peer Reviewed
• [Journal Article] Intensity-Specific and Modified Effects of Physical Activity on Serum Adiponectin in a Middle-Aged Population (2018)
  • Author(s): Nishida Y, Higaki Y, Taguchi N, Hara M, Nakamura K, Nanri H, Imaizumi T, Sakamoto T, Shimanoe C, Horita M, Shinchi K, Tanaka K
  • Journal Title: Journal of the Endocrine Society Volume: 3 Issue: 1 Pages: 13-26
  • DOI: 10.1210/js.2018-00255
  • Peer Reviewed / Open Access
• [Journal Article] Development of suitable method for large-scale urinary glucocorticoid analysis by liquid chromatography-mass spectrometry (2017)
  • Author(s): Matsumoto A, Shimanoe C, Tanaka K, Ichiba M, Hara M
  • Journal Title: J. Chromatography B Volume: 1057 Pages: 62-69
  • DOI: 10.1016/j.jchromb.2017.04.031
  • Peer Reviewed / Open Access
• [Presentation] 尿中cortisol/cortisone比と精神健康との影響：J-MICC Study SAGA. (2020)
  • Author(s): 島ノ江千里，松本明子, 赤穂千穂, 原めぐみ，西田裕一郎，南里妃名子, 堀田美加子, 山田陽介, 檜垣靖樹，田中恵太郎
  • Organizer: 第30回日本疫学会学術総会
• [Presentation] 加速度計により測定された強度別身体活動と血清SPARC濃度の関連 (2020)
  • Author(s): 西田裕一郎，原めぐみ，檜垣靖樹，田口尚人, 島ノ江千里，堀田美加子, 新地浩一, 田中恵太郎
  • Organizer: 第30回日本疫学会学術総会
• [Presentation] 慢性腎臓病と自覚ストレスの関連：J-MICC横断研究. (2020)
  • Author(s): 古賀佳代子, 原めぐみ，島ノ江千里，西田裕一郎，古川拓馬, 田中恵太郎
  • Organizer: 第30回日本疫学会学術総会
• [Presentation] HbA1cに対する身体活動と栄養素摂取の交互作用：J-MICC横断研究 (2020)
  • Author(s): 古川拓馬, 西田裕一郎，原めぐみ，島ノ江千里，古賀佳代子,田中恵太郎
  • Organizer: 第30回日本疫学会学術総会
• [Presentation] Coffee consumption and mortality: a pooled analysis of eight population-based cohort studies (Japan Cohort Consortium). (2019)
  • Author(s): Abe S, Saito E, Sawada N, Tsugane S, Ito H, Lin Y, Tamakoshi A, Kitamura Y, Nagata C, Shimazu T, Matsuo K, Tanaka K, Inoue M
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] 一過性のステップ運動が高齢者の血中SPARC濃度に及ぼす影響． (2019)
  • Author(s): 西田裕一郎，浅香真知子，野出孝一，原めぐみ，田中恵太郎
  • Organizer: 第7回日本介護予防・健康づくり学会大会（福岡）
• [Presentation] 日本人のストレス対処行動に関するGWAS 解析：J-MICC Study (2019)
  • Author(s): 島ノ江千里, 八谷剛史, 原めぐみ, 須藤洋一, 西田裕一郎, 清水厚志, 田中恵太郎
  • Organizer: 第29回日本疫学会学術総会
• [Presentation] 日常身体活動とコーヒー摂取が血清肝逸脱酵素に及ぼす影響 (2019)
  • Author(s): 西田裕一郎, 原めぐみ, 桧垣 靖樹, 田口尚人, 中村和代, 南里妃名子, 今泉猛, 坂本龍彦, 島ノ江千里, 堀田美加子, 新地浩一, 田中恵太郎
  • Organizer: 第29回日本疫学会学術総会
• [Presentation] 郵送法による10年後のコーホート追跡調査への回答と関連する要因：J-MICC Study 佐賀地区 (2019)
  • Author(s): 原めぐみ, 島ノ江千里, 西田裕一郎, 堀田美加子, 田中恵太郎
  • Organizer: 第29回日本疫学会学術総会
• [Presentation] 日本人成人の余暇時間の運動に関するGWAS研究：J-MICC Study (2018)
  • Author(s): 原めぐみ、八谷剛史、西田裕一郎、島ノ江千里、清水厚志、田中恵太郎
  • Organizer: 第28回日本疫学会学術総会
• [Presentation] 日常身体活動とPYCARD遺伝子メチル化の縦断的関連 (2018)
  • Author(s): 西田裕一郎、原めぐみ、桧垣靖樹、田口尚人、島ノ江千里、南里妃名子、中村和代、今泉猛、坂本龍彦、安方惇、三好伸幸、山田陽介、堀田美加子、東元健、副島英伸、新地浩一、田中恵太郎
  • Organizer: 第28回日本疫学会学術総会
• [Presentation] 教育歴と精神ストレスおよび抑うつとの関連について：J-MICC study SAGA (2018)
  • Author(s): 島ノ江 千里、原 めぐみ、西田 裕一郎、南里 妃名子、安方 惇、山田陽介、桧垣靖樹、田中 恵太郎
  • Organizer: 第28回日本疫学会学術総会
• [Presentation] 5年間の精神ストレスとCRPの関連は、対処行動や社会的支援の変化により異なる (2018)
  • Author(s): 島ノ江 千里、原 めぐみ、西田 裕一郎、南里 妃名子、安方 惇、三好信行、山田陽介、桧垣靖樹、田中 恵太郎
  • Organizer: 第88回日本衛生会学術総会
• [Presentation] Mitochondrial haplogroups modify the effect of physical activity on urinary levels of 8-hydroxydeoxyguanosine in middle-aged Japanese subjects (2017)
  • Author(s): Hara M, Nishida Y, Fuku N, Shimanoe C, Nanri H, Taguchi N, Kawai K, Li YS, Kasai H, Higaki Y, Tanaka K.
  • Organizer: The 21st International Epidemiology Association (IEA) ,World Congress of Epidemiology (WCE2017).
  • Int'l Joint Research
• [Presentation] Association between objectively measured physical activity and methylation of PYCARD gene in the Japanese general population (2017)
  • Author(s): Yuichiro Nishida, Yasuki Higaki, Naoto Taguchi, Megumi Hara, Kazuyo Nakamura, Hinako Nanri, Takeshi Imaizumi, Tatsuhiko Sakamoto, Mikako Horita, Koichi Shinchi, Chisato Shimanoe, Ken Higashimoto, Hidenobu Soejima, Keitaro Tanaka
  • Organizer: The 21st International Epidemiological Association (IEA) World Congress of Epidemiology
  • Int'l Joint Research
• [Presentation] 精神ストレスと睡眠の質の関連における情緒的支援の影響は、就業状況によって異なる (2017)
  • Author(s): 島ノ江 千里、原 めぐみ、西田 裕一郎、南里 妃名子、安方 惇、山田陽介、桧垣靖樹、田中 恵太郎
  • Organizer: 第23回日本行動医学会学術総会
• [Presentation] Perceived stress, depressive state, and oxidative DNA damage in a general Japanese population. (2017)
  • Author(s): Shimanoe C, Hara M, Nishida Y, Nanri H, Horita M, Yamada Y, Li Y S, Kasai H, Kawai K, Higaki Y, Tanaka K
  • Organizer: The 21st International Epidemiology Association (IEA) ,World Congress of Epidemiology (WCE2017).
  • Int'l Joint Research
• [Presentation] 心理社会的因子と生活習慣病に介在するバイオマーカーの疫学的検討 ―日本多施設共同コホート研究（J-MICC-study）SAGA－ (2017)
  • Author(s): 島ノ江 千里
  • Organizer: 日本心理学会第81回大会
• [Presentation] Amino acid replacement (K14Q) of mitochondria-derived MOTS-c affects type 2 diabetes in men with lower physical activity (2017)
  • Author(s): Zempo H, Fuku N, Kumagai H, Nishida Y, Higaki Y, Naito H, Hara M, Tanaka K
  • Organizer: The 3rd Congress, International Academy of Sportology
  • Int'l Joint Research
• [Presentation] ミトコンドリアDNA由来ペプチドMOTS-cのアミノ酸置換(K14Q)は身体活動量の低い男性における2型糖尿病に関連する (2017)
  • Author(s): 膳法浩史、福典之、熊谷仁、西田裕一郎、桧垣靖樹、内藤久士、原めぐみ、田中恵太郎
  • Organizer: 第72回日本体力医学会大会
• [Remarks] 佐賀大学医学部社会医学講座予防医学分野ホームページ
  • URL: http://www.prevent.med.saga-u.ac.jp/index.html