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Annual Report 2017

Division of Epidemiology

Motoki Iwasaki, Norie Sawada, Taiki Yamaji, Atsushi Goto, Sanjeev Budhathoki, Ayaka Kotemori, Ryoko Katagiri, Hikaru Ihira, Yoko Shimizu, Tsuyuka Otsuki, Ari Nakamura, Kaori Onda, Jun Umezawa, Eriko Kanehara, Kayo Ohashi, Aya Morishita, Yukari Shiotani, Akihisa Hidaka, Yuko Miyamoto

Introduction

 Our research is aimed at constructing evidence connected to the development of cancer prevention by clarifying the causes of cancer in humans using a study base of a large-scale population-based cohort studies.

Research activities

1. The Japan Public Health Center-based prospective study (JPHC study) / JPHC study for the NEXT generation (JPHC-NEXT)

 Follow-up surveys and data analysis of the Japan Public Health Center-based prospective study (JPHC study) with 140,000 local residents as subjects have been conducted continuously since 1990. In this study, we reported that plasma 25-hydroxyvitamin D concentration was inversely associated with the risk of total cancer, with multivariable adjusted hazard ratios (HRs) for the second to fourth quarters compared with the lowest quarter of 0.81 (95% confidence interval [CI] 0.70 to 0.94), 0.75 (0.65 to 0.87), and 0.78 (0.67 to 0.91), respectively (P for trend=0.001). We found that individuals with constantly high perceived stress level were positively associated with the risk of total cancer compared to subjects with persistently low stress levels (HR=1.11, 95%CI=1.01-1.22). Baseline survey for the JPHC study for the NEXT generation (JPHC-NEXT) completed by the end of 2016 and we obtained questionnaire information from 115,425 participants, and biological samples and information from 58,089 participants (see Table 1 below). The 5-year follow-up survey has started since 2016.

2. Molecular epidemiologic studies to investigate the causes of cancer

 We measured plasma concentrations of leucine, isoleucine and valine in examinees who underwent total colonoscopy as a part of a cancer screening program provided by the National Cancer Center (NCC). In 629 colorectal adenoma (CRA) cases and 584 controls, we observed that high plasma concentrations of leucine, valine and total branched-chain amino acids (BCAAs) were inversely associated with CRA risk: the multivariate-adjusted odds ratios for the highest versus lowest quartiles were 0.60 (95% CI 0.42-0.87) for leucine, 0.68 (0.48-0.97) for valine and 0.68 (0.48-0.98) for total BCAAs. By collaborating with the Breast Cancer Association Consortium (BCAC), we reported 65 new loci associated with overall breast cancer at p<5x10-8, through a genome-wide association study in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry.

3. Consortium on Large-scale Molecular Epidemiologic Studies in Japan

 We have established a consortium on large-scale molecular epidemiologic studies in Japan, which consists of four large-scale studies: the Japan Public Health Center-based Prospective Study (JPHC Study); the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study); the Tohoku Medical Megabank Project (TMM); and the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC). In this consortium, we set up a protocol for performing genome wide association studies (GWAS) for height, weight, and body mass index, all of which are related to the risk of cancer incidence. GWAS results are gathered and meta-analysis is being carried out. Further, in order to promote the collab-orative research system, we built a platform within the NCC that enables remote-access to the data-base and supercomputers at Tohoku University.

Education

 Supervised the research of two graduate students and one research resident fellowship.

Future prospects

 While focusing on the cohort structure of the JPHC study for the next generation (JPHC-NEXT) that becomes the study base, we hope to contribute to the development of cancer prevention through the analysis of information and samples of existing epidemiologic studies by identifying new risk factors and the continued evaluation of risks in Japanese people.

Table 1. Study areas and results of baseline survey in the JPHC for the NEXT generation (JPHC-NEXT)
Table 1. Study areas and results of baseline survey in the JPHC for the NEXT generation (JPHC-NEXT)

Table 1. Study areas and results of baseline survey in the JPHC for the NEXT generation (JPHC-NEXT)
Table 1. Study areas and results of baseline survey in the JPHC for the NEXT generation (JPHC-NEXT)(Full Size)

List of papers published in January 2017 - March 2018

Journal

 1. Makiuchi T, Sobue T, Kitamura T, Sawada N, Iwasaki M, Sasazuki S, Yamaji T, Shimazu T, Tsugane S. Reproductive factors and gallbladder/bile duct cancer: a population-based cohort study in Japan. Eur J Cancer Prev, 26:292-300, 2017

 2. Milne RL, Kuchenbaecker KB, Michailidou K, Beesley J, Kar S, Lindstrom S, Hui S, Lemacon A, Soucy P, Dennis J, Jiang X, Rostamianfar A, Finucane H, Bolla MK, McGuffog L, Wang Q, Aalfs CM, Adams M, Adlard J, Agata S, Ahmed S, Ahsan H, Aittomaki K, Al-Ejeh F, Allen J, Ambrosone CB, Amos CI, Andrulis IL, Anton-Culver H, Antonenkova NN, Arndt V, Arnold N, Aronson KJ, Auber B, Auer PL, Ausems MGEM, Azzollini J, Bacot F, Balmana J, Barile M, Barjhoux L, Barkardottir RB, Barrdahl M, Barnes D, Barrowdale D, Baynes C, Beckmann MW, Benitez J, Bermisheva M, Bernstein L, Bignon YJ, Blazer KR, Blok MJ, Blomqvist C, Blot W, Bobolis K, Boeckx B, Bogdanova NV, Bojesen A, Bojesen SE, Bonanni B, Borresen-Dale AL, Bozsik A, Bradbury AR, Brand JS, Brauch H, Brenner H, Bressac-de Paillerets B, Brewer C, Brinton L, Broberg P, Brooks-Wilson A, Brunet J, Bruning T, Burwinkel B, Buys SS, Byun J, Cai Q, Caldes T, Caligo MA, Campbell I, Canzian F, Caron O, Carracedo A, Carter BD, Castelao JE, Castera L, Caux-Moncoutier V, Chan SB, Chang-Claude J, Chanock SJ, Chen X, Cheng TD, Chiquette J, Christiansen H, Claes KBM, Clarke CL, Conner T, Conroy DM, Cook J, Cordina-Duverger E, Cornelissen S, Coupier I, Cox A, Cox DG, Cross SS, Cuk K, Cunningham JM, Czene K, Daly MB, Damiola F, Darabi H, Davidson R, De Leeneer K, Devilee P, Dicks E, Diez O, Ding YC, Ditsch N, Doheny KF, Domchek SM, Dorfling CM, Dork T, Dos-Santos-Silva I, Dubois S, Dugue PA, Dumont M, Dunning AM, Durcan L, Dwek M, Dworniczak B, Eccles D, Eeles R, Ehrencrona H, Eilber U, Ejlertsen B, Ekici AB, Eliassen AH, Engel C, Eriksson M, Fachal L, Faivre L, Fasching PA, Faust U, Figueroa J, Flesch-Janys D, Fletcher O, Flyger H, Foulkes WD, Friedman E, Fritschi L, Frost D, Gabrielson M, Gaddam P, Gammon MD, Ganz PA, Gapstur SM, Garber J, Garcia-Barberan V, Garcia-Saenz JA, Gaudet MM, Gauthier-Villars M, Gehrig A, Georgoulias V, Gerdes AM, Giles GG, Glendon G, Godwin AK, Goldberg MS, Goldgar DE, Gonzalez-Neira A, Goodfellow P, Greene MH, Alnaes GIG, Grip M, Gronwald J, Grundy A, Gschwantler-Kaulich D, Guenel P, Guo Q, Haeberle L, Hahnen E, Haiman CA, Hakansson N, Hallberg E, Hamann U, Hamel N, Hankinson S, Hansen TVO, Harrington P, Hart SN, Hartikainen JM, Healey CS, Hein A, Helbig S, Henderson A, Heyworth J, Hicks B, Hillemanns P, Hodgson S, Hogervorst FB, Hollestelle A, Hooning MJ, Hoover B, Hopper JL, Hu C, Huang G, Hulick PJ, Humphreys K, Hunter DJ, Imyanitov EN, Isaacs C, Iwasaki M, Izatt L, Jakubowska A, James P, Janavicius R, Janni W, Jensen UB, John EM, Johnson N, Jones K, Jones M, Jukkola-Vuorinen A, Kaaks R, Kabisch M, Kaczmarek K, Kang D, Kast K, Keeman R, Kerin MJ, Kets CM, Keupers M, Khan S, Khusnutdinova E, Kiiski JI, Kim SW, Knight JA, Konstantopoulou I, Kosma VM, Kristensen VN, Kruse TA, Kwong A, Laenkholm AV, Laitman Y, Lalloo F, Lambrechts D, Landsman K, Lasset C, Lazaro C, Le Marchand L, Lecarpentier J, Lee A, Lee E, Lee JW, Lee MH, Lejbkowicz F, Lesueur F, Li J, Lilyquist J, Lincoln A, Lindblom A, Lissowska J, Lo WY, Loibl S, Long J, Loud JT, Lubinski J, Luccarini C, Lush M, MacInnis RJ, Maishman T, Makalic E, Kostovska IM, Malone KE, Manoukian S, Manson JE, Margolin S, Martens JWM, Martinez ME, Matsuo K, Mavroudis D, Mazoyer S, McLean C, Meijers-Heijboer H, Menendez P, Meyer J, Miao H, Miller A, Miller N, Mitchell G, Montagna M, Muir K, Mulligan AM, Mulot C, Nadesan S, Nathanson KL, Neuhausen SL, Nevanlinna H, Nevelsteen I, Niederacher D, Nielsen SF, Nordestgaard BG, Norman A, Nussbaum RL, Olah E, Olopade OI, Olson JE, Olswold C, Ong KR, Oosterwijk JC, Orr N, Osorio A, Pankratz VS, Papi L, Park-Simon TW, Paulsson-Karlsson Y, Lloyd R, Pedersen IS, Peissel B, Peixoto A, Perez JIA, Peterlongo P, Peto J, Pfeiler G, Phelan CM, Pinchev M, Plaseska-Karanfilska D, Poppe B, Porteous ME, Prentice R, Presneau N, Prokofieva D, Pugh E, Pujana MA, Pylkas K, Rack B, Radice P, Rahman N, Rantala J, Rappaport-Fuerhauser C, Rennert G, Rennert HS, Rhenius V, Rhiem K, Richardson A, Rodriguez GC, Romero A, Romm J, Rookus MA, Rudolph A, Ruediger T, Saloustros E, Sanders J, Sandler DP, Sangrajrang S, Sawyer EJ, Schmidt DF, Schoemaker MJ, Schumacher F, Schurmann P, Schwentner L, Scott C, Scott RJ, Seal S, Senter L, Seynaeve C, Shah M, Sharma P, Shen CY, Sheng X, Shimelis H, Shrubsole MJ, Shu XO, Side LE, Singer CF, Sohn C, Southey MC, Spinelli JJ, Spurdle AB, Stegmaier C, Stoppa-Lyonnet D, Sukiennicki G, Surowy H, Sutter C, Swerdlow A, Szabo CI, Tamimi RM, Tan YY, Taylor JA, Tejada MI, Tengstrom M, Teo SH, Terry MB, Tessier DC, Teule A, Thone K, Thull DL, Tibiletti MG, Tihomirova L, Tischkowitz M, Toland AE, Tollenaar RAEM, Tomlinson I, Tong L, Torres D, Tranchant M, Truong T, Tucker K, Tung N, Tyrer J, Ulmer HU, Vachon C, van Asperen CJ, Van Den Berg D, van den Ouweland AMW, van Rensburg EJ, Varesco L, Varon-Mateeva R, Vega A, Viel A, Vijai J, Vincent D, Vollenweider J, Walker L, Wang Z, Wang-Gohrke S, Wappenschmidt B, Weinberg CR, Weitzel JN, Wendt C, Wesseling J, Whittemore AS, Wijnen JT, Willett W, Winqvist R, Wolk A, Wu AH, Xia L, Yang XR, Yannoukakos D, Zaffaroni D, Zheng W, Zhu B, Ziogas A, Ziv E, Zorn KK, Gago-Dominguez M, Mannermaa A, Olsson H, Teixeira MR, Stone J, Offit K, Ottini L, Park SK, Thomassen M, Hall P, Meindl A, Schmutzler RK, Droit A, Bader GD, Pharoah PDP, Couch FJ, Easton DF, Kraft P, Chenevix-Trench G, Garcia-Closas M, Schmidt MK, Antoniou AC, Simard J. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nat Genet, 49:1767-1778, 2017

 3. Michailidou K, Lindstrom S, Dennis J, Beesley J, Hui S, Kar S, Lemacon A, Soucy P, Glubb D, Rostamianfar A, Bolla MK, Wang Q, Tyrer J, Dicks E, Lee A, Wang Z, Allen J, Keeman R, Eilber U, French JD, Qing Chen X, Fachal L, McCue K, McCart Reed AE, Ghoussaini M, Carroll JS, Jiang X, Finucane H, Adams M, Adank MA, Ahsan H, Aittomaki K, Anton-Culver H, Antonenkova NN, Arndt V, Aronson KJ, Arun B, Auer PL, Bacot F, Barrdahl M, Baynes C, Beckmann MW, Behrens S, Benitez J, Bermisheva M, Bernstein L, Blomqvist C, Bogdanova NV, Bojesen SE, Bonanni B, Borresen-Dale AL, Brand JS, Brauch H, Brennan P, Brenner H, Brinton L, Broberg P, Brock IW, Broeks A, Brooks-Wilson A, Brucker SY, Bruning T, Burwinkel B, Butterbach K, Cai Q, Cai H, Caldes T, Canzian F, Carracedo A, Carter BD, Castelao JE, Chan TL, David Cheng TY, Seng Chia K, Choi JY, Christiansen H, Clarke CL, Collee M, Conroy DM, Cordina-Duverger E, Cornelissen S, Cox DG, Cox A, Cross SS, Cunningham JM, Czene K, Daly MB, Devilee P, Doheny KF, Dork T, Dos-Santos-Silva I, Dumont M, Durcan L, Dwek M, Eccles DM, Ekici AB, Eliassen AH, Ellberg C, Elvira M, Engel C, Eriksson M, Fasching PA, Figueroa J, Flesch-Janys D, Fletcher O, Flyger H, Fritschi L, Gaborieau V, Gabrielson M, Gago-Dominguez M, Gao YT, Gapstur SM, Garcia-Saenz JA, Gaudet MM, Georgoulias V, Giles GG, Glendon G, Goldberg MS, Goldgar DE, Gonzalez-Neira A, Grenaker Alnaes GI, Grip M, Gronwald J, Grundy A, Guenel P, Haeberle L, Hahnen E, Haiman CA, Hakansson N, Hamann U, Hamel N, Hankinson S, Harrington P, Hart SN, Hartikainen JM, Hartman M, Hein A, Heyworth J, Hicks B, Hillemanns P, Ho DN, Hollestelle A, Hooning MJ, Hoover RN, Hopper JL, Hou MF, Hsiung CN, Huang G, Humphreys K, Ishiguro J, Ito H, Iwasaki M, Iwata H, Jakubowska A, Janni W, John EM, Johnson N, Jones K, Jones M, Jukkola-Vuorinen A, Kaaks R, Kabisch M, Kaczmarek K, Kang D, Kasuga Y, Kerin MJ, Khan S, Khusnutdinova E, Kiiski JI, Kim SW, Knight JA, Kosma VM, Kristensen VN, Kruger U, Kwong A, Lambrechts D, Le Marchand L, Lee E, Lee MH, Lee JW, Neng Lee C, Lejbkowicz F, Li J, Lilyquist J, Lindblom A, Lissowska J, Lo WY, Loibl S, Long J, Lophatananon A, Lubinski J, Luccarini C, Lux MP, Ma ESK, MacInnis RJ, Maishman T, Makalic E, Malone KE, Kostovska IM, Mannermaa A, Manoukian S, Manson JE, Margolin S, Mariapun S, Martinez ME, Matsuo K, Mavroudis D, McKay J, McLean C, Meijers-Heijboer H, Meindl A, Menendez P, Menon U, Meyer J, Miao H, Miller N, Taib NAM, Muir K, Mulligan AM, Mulot C, Neuhausen SL, Nevanlinna H, Neven P, Nielsen SF, Noh DY, Nordestgaard BG, Norman A, Olopade OI, Olson JE, Olsson H, Olswold C, Orr N, Pankratz VS, Park SK, Park-Simon TW, Lloyd R, Perez JIA, Peterlongo P, Peto J, Phillips KA, Pinchev M, Plaseska-Karanfilska D, Prentice R, Presneau N, Prokofyeva D, Pugh E, Pylkas K, Rack B, Radice P, Rahman N, Rennert G, Rennert HS, Rhenius V, Romero A, Romm J, Ruddy KJ, Rudiger T, Rudolph A, Ruebner M, Rutgers EJT, Saloustros E, Sandler DP, Sangrajrang S, Sawyer EJ, Schmidt DF, Schmutzler RK, Schneeweiss A, Schoemaker MJ, Schumacher F, Schurmann P, Scott RJ, Scott C, Seal S, Seynaeve C, Shah M, Sharma P, Shen CY, Sheng G, Sherman ME, Shrubsole MJ, Shu XO, Smeets A, Sohn C, Southey MC, Spinelli JJ, Stegmaier C, Stewart-Brown S, Stone J, Stram DO, Surowy H, Swerdlow A, Tamimi R, Taylor JA, Tengstrom M, Teo SH, Beth Terry M, Tessier DC, Thanasitthichai S, Thone K, Tollenaar RAEM, Tomlinson I, Tong L, Torres D, Truong T, Tseng CC, Tsugane S, Ulmer HU, Ursin G, Untch M, Vachon C, van Asperen CJ, Van Den Berg D, van den Ouweland AMW, van der Kolk L, van der Luijt RB, Vincent D, Vollenweider J, Waisfisz Q, Wang-Gohrke S, Weinberg CR, Wendt C, Whittemore AS, Wildiers H, Willett W, Winqvist R, Wolk A, Wu AH, Xia L, Yamaji T, Yang XR, Har Yip C, Yoo KY, Yu JC, Zheng W, Zheng Y, Zhu B, Ziogas A, Ziv E, Lakhani SR, Antoniou AC, Droit A, Andrulis IL, Amos CI, Couch FJ, Pharoah PDP, Chang-Claude J, Hall P, Hunter DJ, Milne RL, Garcia-Closas M, Schmidt MK, Chanock SJ, Dunning AM, Edwards SL, Bader GD, Chenevix-Trench G, Simard J, Kraft P, Easton DF. Association analysis identifies 65 new breast cancer risk loci. Nature, 551:92-94, 2017

 4. Kato E, Takachi R, Ishihara J, Ishii Y, Sasazuki S, Sawada N, Iwasaki M, Shinozawa Y, Umezawa J, Tanaka J, Yokoyama Y, Kitamura K, Nakamura K, Tsugane S. Online version of the self-administered food frequency questionnaire for the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT) protocol: Relative validity, usability, and comparison with a printed questionnaire. J Epidemiol, 27:435-446, 2017

 5. Sawada N, Wark PA, Merritt MA, Tsugane S, Ward HA, Rinaldi S, Weiderpass E, Dartois L, His M, Boutron-Ruault MC, Turzanski-Fortner R, Kaaks R, Overvad K, Redondo ML, Travier N, Molina-Portillo E, Dorronsoro M, Cirera L, Ardanaz E, Perez-Cornago A, Trichopoulou A, Lagiou P, Valanou E, Masala G, Pala V, Hm Peeters P, T van der Schouw Y, Melander O, Manjer J, da Silva M, Skeie G, Tjonneland A, Olsen A, J Gunter M, Riboli E, J Cross A. The association between adult attained height and sitting height with mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC). PLoS One, 12:e0173117, 2017

 6. Sako A, Yasunaga H, Matsui H, Fushimi K, Hamasaki H, Katsuyama H, Tsujimoto T, Goto A, Yanai H. Hospitalization with hypoglycemia in patients without diabetes mellitus: A retrospective study using a national inpatient database in Japan, 2008-2012. Medicine (Baltimore), 96:e7271, 2017

 7. Yu D, Takata Y, Smith-Warner SA, Blot W, Sawada N, White E, Freedman N, Robien K, Giovannucci E, Zhang X, Park Y, Gao YT, Chlebowski RT, Langhammer A, Yang G, Severi G, Manjer J, Khaw KT, Weiderpass E, Liao LM, Caporaso N, Krokstad S, Hveem K, Sinha R, Ziegler R, Tsugane S, Xiang YB, Johansson M, Zheng W, Shu XO. Prediagnostic Calcium Intake and Lung Cancer Survival: A Pooled Analysis of 12 Cohort Studies. Cancer Epidemiol Biomarkers Prev, 26:1060-1070, 2017

 8. Chen Y, Wu F, Saito E, Lin Y, Song M, Luu HN, Gupta PC, Sawada N, Tamakoshi A, Shu XO, Koh WP, Xiang YB, Tomata Y, Sugiyama K, Park SK, Matsuo K, Nagata C, Sugawara Y, Qiao YL, You SL, Wang R, Shin MH, Pan WH, Pednekar MS, Tsugane S, Cai H, Yuan JM, Gao YT, Tsuji I, Kanemura S, Ito H, Wada K, Ahn YO, Yoo KY, Ahsan H, Chia KS, Boffetta P, Zheng W, Inoue M, Kang D, Potter JD. Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium. Diabetologia, 60:1022-1032, 2017

 9. Katanoda K, Noda M, Goto A, Mizunuma H, Lee JS, Hayashi K. Impact of birth weight on adult-onset diabetes mellitus in relation to current body mass index: The Japan Nurses' Health Study. J Epidemiol, 27:428-434, 2017

10. Kigawa N, Budhathoki S, Yamaji T, Iwasaki M, Inoue M, Tsugane S. Association of plasma C-reactive protein level with the prevalence of colorectal adenoma: the Colorectal Adenoma Study in Tokyo. Sci Rep, 7:4456, 2017

11. Wang C, Nishiyama T, Kikuchi S, Inoue M, Sawada N, Tsugane S, Lin Y. Changing trends in the prevalence of H. pylori infection in Japan (1908-2003): a systematic review and meta-regression analysis of 170,752 individuals. Sci Rep, 7:15491, 2017

12. Ishii Y, Ishihara J, Takachi R, Shinozawa Y, Imaeda N, Goto C, Wakai K, Takahashi T, Iso H, Nakamura K, Tanaka J, Shimazu T, Yamaji T, Sasazuki S, Sawada N, Iwasaki M, Mikami H, Kuriki K, Naito M, Okamoto N, Kondo F, Hosono S, Miyagawa N, Ozaki E, Katsuura-Kamano S, Ohnaka K, Nanri H, Tsunematsu-Nakahata N, Kayama T, Kurihara A, Kojima S, Tanaka H, Tsugane S. Comparison of weighed food record procedures for the reference methods in two validation studies of food frequency questionnaires. J Epidemiol, 27:331-337, 2017

13. Dong JY, Iso H, Yamagishi K, Sawada N, Tsugane S. Chocolate consumption and risk of stroke among men and women: A large population-based, prospective cohort study. Atherosclerosis, 260:8-12, 2017

14. Sawada N, Inoue M, Iwasaki M, Yamaji T, Shimazu T, Sasazuki S, Tsugane S. Plasma 25-hydroxy vitamin D and subsequent prostate cancer risk in a nested Case-Control study in Japan: The JPHC study. Eur J Clin Nutr, 71:132-136, 2017

15. Koda M, Iwasaki M, Yamano Y, Lu X, Katoh T. Association between NAT2, CYP1A1, and CYP1A2 genotypes, heterocyclic aromatic amines, and prostate cancer risk: a case control study in Japan. Environ Health Prev Med, 22:72, 2017

16. Uesugi S, Ishihara J, Iso H, Sawada N, Takachi R, Inoue M, Tsugane S. Dietary intake of antioxidant vitamins and risk of stroke: the Japan Public Health Center-based Prospective Study. Eur J Clin Nutr, 71:1179-1185, 2017

17. Narita S, Inoue M, Saito E, Abe SK, Sawada N, Ishihara J, Iwasaki M, Yamaji T, Shimazu T, Sasazuki S, Shibuya K, Tsugane S. Dietary fiber intake and risk of breast cancer defined by estrogen and progesterone receptor status: the Japan Public Health Center-based Prospective Study. Cancer Causes Control, 28:569-578, 2017

18. Makiuchi T, Sobue T, Kitamura T, Ishihara J, Sawada N, Iwasaki M, Sasazuki S, Yamaji T, Shimazu T, Tsugane S. The relationship between vegetable/fruit consumption and gallbladder/bile duct cancer: A population-based cohort study in Japan. Int J Cancer, 140:1009-1019, 2017

19. Ugai T, Matsuo K, Sawada N, Iwasaki M, Yamaji T, Shimazu T, Sasazuki S, Inoue M, Kanda Y, Tsugane S. Smoking and alcohol and subsequent risk of myelodysplastic syndromes in Japan: the Japan Public Health Centre-based Prospective Study. Br J Haematol, 178:747-755, 2017

20. Akter S, Goto A, Mizoue T. Smoking and the risk of type 2 diabetes in Japan: A systematic review and meta-analysis. J Epidemiol, 27:553-561, 2017

21. Nozue M, Shimazu T, Sasazuki S, Charvat H, Mori N, Mutoh M, Sawada N, Iwasaki M, Yamaji T, Inoue M, Kokubo Y, Yamagishi K, Iso H, Tsugane S. Fermented Soy Product Intake Is Inversely Associated with the Development of High Blood Pressure: The Japan Public Health Center-Based Prospective Study. J Nutr, 147:1749-1756, 2017

22. Iwasaki M, Tanaka-Mizuno S, Kuchiba A, Yamaji T, Sawada N, Goto A, Shimazu T, Sasazuki S, Wang H, Marchand LL, Tsugane S. Inclusion of a Genetic Risk Score into a Validated Risk Prediction Model for Colorectal Cancer in Japanese Men Improves Performance. Cancer Prev Res (Phila), 10:535-541, 2017

23. Teng Y, Saito E, Abe SK, Sawada N, Iwasaki M, Yamaji T, Shimazu T, Sasazuki S, Inoue M, Tsugane S. Female reproductive factors, exogenous hormone use, and pancreatic cancer risk: the Japan Public Health Center-based prospective study. Eur J Cancer Prev, 26:378-384, 2017

24. Mori N, Shimazu T, Sasazuki S, Nozue M, Mutoh M, Sawada N, Iwasaki M, Yamaji T, Inoue M, Takachi R, Sunami A, Ishihara J, Sobue T, Tsugane S. Cruciferous Vegetable Intake Is Inversely Associated with Lung Cancer Risk among Current Nonsmoking Men in the Japan Public Health Center (JPHC) Study. J Nutr, 147:841-849, 2017

25. Eshak ES, Honjo K, Iso H, Ikeda A, Inoue M, Sawada N, Tsugane S. Changes in the Employment Status and Risk of Stroke and Stroke Types. Stroke, 48:1176-1182, 2017

26. Ugai T, Matsuo K, Sawada N, Iwasaki M, Yamaji T, Shimazu T, Sasazuki S, Inoue M, Kanda Y, Tsugane S. Coffee and Green Tea Consumption and Subsequent Risk of Malignant Lymphoma and Multiple Myeloma in Japan: The Japan Public Health Center-based Prospective Study. Cancer Epidemiol Biomarkers Prev, 26:1352-1356, 2017

27. Kubota Y, Iso H, Yamagishi K, Sawada N, Tsugane S. Daily Total Physical Activity and Incident Cardiovascular Disease in Japanese Men and Women: Japan Public Health Center-Based Prospective Study. Circulation, 135:1471-1473, 2017

28. Hamasaki H, Kawashima Y, Katsuyama H, Sako A, Goto A, Yanai H. Association of handgrip strength with hospitalization, cardiovascular events, and mortality in Japanese patients with type 2 diabetes. Sci Rep, 7:7041, 2017

29. Ugai T, Matsuo K, Sawada N, Iwasaki M, Yamaji T, Shimazu T, Sasazuki S, Inoue M, Tsugane S. Smoking and subsequent risk of leukemia in Japan: The Japan Public Health Center-based Prospective Study. J Epidemiol, 27:305-310, 2017

30. Watts EL, Appleby PN, Albanes D, Black A, Chan JM, Chen C, Cirillo PM, Cohn BA, Cook MB, Donovan JL, Ferrucci L, Garland CF, Giles GG, Goodman PJ, Habel LA, Haiman CA, Holly JMP, Hoover RN, Kaaks R, Knekt P, Kolonel LN, Kubo T, Le Marchand L, Luostarinen T, MacInnis RJ, Maenpaa HO, Mannisto S, Metter EJ, Milne RL, Nomura AMY, Oliver SE, Parsons JK, Peeters PH, Platz EA, Riboli E, Ricceri F, Rinaldi S, Rissanen H, Sawada N, Schaefer CA, Schenk JM, Stanczyk FZ, Stampfer M, Stattin P, Stenman UH, Tjonneland A, Trichopoulou A, Thompson IM, Tsugane S, Vatten L, Whittemore AS, Ziegler RG, Allen NE, Key TJ, Travis RC. Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men. PLoS One, 12:e0187741, 2017

31. Eshak ES, Iso H, Honjo K, Noda A, Sawada N, Tsugane S. Changes in the living arrangement and risk of stroke in Japan; does it matter who lives in the household? Who among the family matters? PLoS One, 12:e0173860, 2017

32. Goto A, Noda M, Goto M, Yasuda K, Mizoue T, Yamaji T, Sawada N, Iwasaki M, Inoue M, Tsugane S. Plasma adiponectin levels, ADIPOQ variants, and incidence of type 2 diabetes: A nested case-control study. Diabetes Res Clin Pract, 127:254-264, 2017

33. Low SK, Takahashi A, Ebana Y, Ozaki K, Christophersen IE, Ellinor PT, Ogishima S, Yamamoto M, Satoh M, Sasaki M, Yamaji T, Iwasaki M, Tsugane S, Tanaka K, Naito M, Wakai K, Tanaka H, Furukawa T, Kubo M, Ito K, Kamatani Y, Tanaka T. Identification of six new genetic loci associated with atrial fibrillation in the Japanese population. Nat Genet, 49:953-958, 2017

34. Hachiya T, Kamatani Y, Takahashi A, Hata J, Furukawa R, Shiwa Y, Yamaji T, Hara M, Tanno K, Ohmomo H, Ono K, Takashima N, Matsuda K, Wakai K, Sawada N, Iwasaki M, Yamagishi K, Ago T, Ninomiya T, Fukushima A, Hozawa A, Minegishi N, Satoh M, Endo R, Sasaki M, Sakata K, Kobayashi S, Ogasawara K, Nakamura M, Hitomi J, Kita Y, Tanaka K, Iso H, Kitazono T, Kubo M, Tanaka H, Tsugane S, Kiyohara Y, Yamamoto M, Sobue K, Shimizu A. Genetic Predisposition to Ischemic Stroke: A Polygenic Risk Score. Stroke, 48:253-258, 2017

35. Nanri A, Mizoue T, Shimazu T, Ishihara J, Takachi R, Noda M, Iso H, Sasazuki S, Sawada N, Tsugane S. Dietary patterns and all-cause, cancer, and cardiovascular disease mortality in Japanese men and women: The Japan public health center-based prospective study. PLoS One, 12:e0174848, 2017

36. Petimar J, Wilson KM, Wu K, Wang M, Albanes D, van den Brandt PA, Cook MB, Giles GG, Giovannucci EL, Goodman GE, Goodman PJ, Hakansson N, Helzlsouer K, Key TJ, Kolonel LN, Liao LM, Mannisto S, McCullough ML, Milne RL, Neuhouser ML, Park Y, Platz EA, Riboli E, Sawada N, Schenk JM, Tsugane S, Verhage B, Wang Y, Wilkens LR, Wolk A, Ziegler RG, Smith-Warner SA. A Pooled Analysis of 15 Prospective Cohort Studies on the Association between Fruit, Vegetable, and Mature Bean Consumption and Risk of Prostate Cancer. Cancer Epidemiol Biomarkers Prev, 26:1276-1287, 2017

37. Tabuchi T, Goto A, Ito Y, Fukui K, Miyashiro I, Shinozaki T. Smoking at the time of diagnosis and mortality in cancer patients: What benefit does the quitter gain? Int J Cancer, 140:1789-1795, 2017

38. Budhathoki S, Iwasaki M, Yamaji T, Yamamoto H, Kato Y, Tsugane S. Association of plasma concentrations of branched-chain amino acids with risk of colorectal adenoma in a large Japanese population. Ann Oncol, 28:818-823, 2017

39. Masaoka H, Matsuo K, Sawada N, Yamaji T, Goto A, Shimazu T, Iwasaki M, Inoue M, Eto M, Tsugane S. Alcohol consumption and bladder cancer risk with or without the flushing response: The Japan Public Health Center-based Prospective Study. Int J Cancer, 141:2480-2488, 2017

40. Seow WJ, Matsuo K, Hsiung CA, Shiraishi K, Song M, Kim HN, Wong MP, Hong YC, Wang Z, Chang IS, Wang JC, Chatterjee N, Tucker M, Wei H, Mitsudomi T, Zheng W, Kim JH, Zhou B, Caporaso NE, Albanes D, Shin MH, Chung LP, An SJ, Wang P, Zheng H, Yatabe Y, Zhang XC, Kim YT, Shu XO, Kim YC, Bassig BA, Chang J, Ho JCM, Ji BT, Kubo M, Daigo Y, Ito H, Momozawa Y, Ashikawa K, Kamatani Y, Honda T, Sakamoto H, Kunitoh H, Tsuta K, Watanabe S, Nokihara H, Miyagi Y, Nakayama H, Matsumoto S, Tsuboi M, Goto K, Yin Z, Shi J, Takahashi A, Goto A, Minamiya Y, Shimizu K, Tanaka K, Wu T, Wei F, Wong JYY, Matsuda F, Su J, Kim YH, Oh IJ, Song F, Lee VHF, Su WC, Chen YM, Chang GC, Chen KY, Huang MS, Yang PC, Lin HC, Xiang YB, Seow A, Park JY, Kweon SS, Chen CJ, Li H, Gao YT, Wu C, Qian B, Lu D, Liu J, Jeon HS, Hsiao CF, Sung JS, Tsai YH, Jung YJ, Guo H, Hu Z, Wang WC, Chung CC, Lawrence C, Burdett L, Yeager M, Jacobs KB, Hutchinson A, Berndt SI, He X, Wu W, Wang J, Li Y, Choi JE, Park KH, Sung SW, Liu L, Kang CH, Hu L, Chen CH, Yang TY, Xu J, Guan P, Tan W, Wang CL, Sihoe ADL, Chen Y, Choi YY, Hung JY, Kim JS, Yoon HI, Cai Q, Lin CC, Park IK, Xu P, Dong J, Kim C, He Q, Perng RP, Chen CY, Vermeulen R, Wu J, Lim WY, Chen KC, Chan JKC, Chu M, Li YJ, Li J, Chen H, Yu CJ, Jin L, Lo YL, Chen YH, Liu J, Yamaji T, Yang Y, Hicks B, Wyatt K, Li SA, Dai J, Ma H, Jin G, Song B, Wang Z, Cheng S, Li X, Ren Y, Cui P, Iwasaki M, Shimazu T, Tsugane S, Zhu J, Jiang G, Fei K, Wu G, Chien LH, Chen HL, Su YC, Tsai FY, Chen YS, Yu J, Stevens VL, Laird-Offringa IA, Marconett CN, Lin D, Chen K, Wu YL, Landi MT, Shen H, Rothman N, Kohno T, Chanock SJ, Lan Q. Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations. Hum Mol Genet, 26:454-465, 2017

41. Saito I, Yamagishi K, Kokubo Y, Yatsuya H, Iso H, Sawada N, Inoue M, Tsugane S. Association of high-density lipoprotein cholesterol concentration with different types of stroke and coronary heart disease: The Japan Public Health Center-based prospective (JPHC) study. Atherosclerosis, 265:147-154, 2017

42. Akiyama M, Okada Y, Kanai M, Takahashi A, Momozawa Y, Ikeda M, Iwata N, Ikegawa S, Hirata M, Matsuda K, Iwasaki M, Yamaji T, Sawada N, Hachiya T, Tanno K, Shimizu A, Hozawa A, Minegishi N, Tsugane S, Yamamoto M, Kubo M, Kamatani Y. Genome-wide association study identifies 112 new loci for body mass index in the Japanese population. Nat Genet, 49:1458-1467, 2017

43. Sawada N. Risk and preventive factors for prostate cancer in Japan: The Japan Public Health Center-based prospective (JPHC) study. J Epidemiol, 27:2-7, 2017

44. Matsuoka YJ, Sawada N, Mimura M, Shikimoto R, Nozaki S, Hamazaki K, Uchitomi Y, Tsugane S. Dietary fish, n-3 polyunsaturated fatty acid consumption, and depression risk in Japan: a population-based prospective cohort study. Transl Psychiatry, 7:e1242, 2017

45. Song H, Saito E, Sawada N, Abe SK, Hidaka A, Shimazu T, Yamaji T, Goto A, Iwasaki M, Sasazuki S, Ye W, Inoue M, Tsugane S. Body mass index change during adulthood and risk of oesophageal squamous-cell carcinoma in a Japanese population: the Japan Public Health (JPHC)-based prospective study. Br J Cancer, 117:1715-1722, 2017

46. Nishiumi S, Kobayashi T, Kawana S, Unno Y, Sakai T, Okamoto K, Yamada Y, Sudo K, Yamaji T, Saito Y, Kanemitsu Y, Okita NT, Saito H, Tsugane S, Azuma T, Ojima N, Yoshida M. Investigations in the possibility of early detection of colorectal cancer by gas chromatography/triple-quadrupole mass spectrometry. Oncotarget, 8:17115-17126, 2017

47. Akter S, Nanri A, Mizoue T, Noda M, Sawada N, Sasazuki S, Tsugane S. Dietary acid load and mortality among Japanese men and women: the Japan Public Health Center-based Prospective Study. Am J Clin Nutr, 106:146-154, 2017

48. Horita N, Goto A, Shibata Y, Ota E, Nakashima K, Nagai K, Kaneko T. Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev, 2:CD012066, 2017

49. Svensson T, Inoue M, Sawada N, Charvat H, Mimura M, Tsugane S. High serum total cholesterol is associated with suicide mortality in Japanese women. Acta Psychiatr Scand, 136:259-268, 2017

50. Okada C, Iso H, Ishihara J, Maruyama K, Sawada N, Tsugane S. Validity and reliability of a self-administered food frequency questionnaire for the JPHC study: The assessment of amino acid intake. J Epidemiol, 27:242-247, 2017

51. Kobayashi T, Honjo K, Eshak ES, Iso H, Sawada N, Tsugane S. Work-family conflict and self-rated health among Japanese workers: How household income modifies associations. PLoS One, 12:e0169903, 2017

52. Song H, Saito E, Sawada N, Abe SK, Hidaka A, Shimazu T, Yamaji T, Goto A, Iwasaki M, Sasazuki S, Ye W, Inoue M, Tsugane S. Perceived stress level and risk of cancer incidence in a Japanese population: the Japan Public Health Center (JPHC)-based Prospective Study. Sci Rep, 7:12964, 2017

53. Kubota Y, Iso H, Yamagishi K, Sawada N, Tsugane S. Daily Total Physical Activity and Incident Stroke: The Japan Public Health Center-Based Prospective Study. Stroke, 48:1730-1736, 2017

54. Horita N, Nagashima A, Nakashima K, Shibata Y, Ito K, Goto A, Yamanaka T, Kaneko T. The best platinum regimens for chemo-naive incurable non-small cell lung cancer: network meta-analysis. Sci Rep, 7:13185, 2017

55. Pandey JP, Namboodiri AM, Wolf B, Iwasaki M, Kasuga Y, Hamada GS, Tsugane S. Endogenous antibody responses to mucin 1 in a large multiethnic cohort of patients with breast cancer and healthy controls: Role of immunoglobulin and Fcgamma receptor genes. Immunobiology, 223:178-182, 2018

56. Ugai T, Matsuo K, Sawada N, Iwasaki M, Yamaji T, Shimazu T, Goto A, Inoue M, Kanda Y, Tsugane S. Coffee and green tea consumption and subsequent risk of acute myeloid leukemia and myelodysplastic syndromes in Japan. Int J Cancer, 142:1130-1138, 2018

57. Saito E, Inoue M, Sawada N, Charvat H, Shimazu T, Yamaji T, Iwasaki M, Sasazuki S, Mizoue T, Iso H, Tsugane S. Impact of Alcohol Intake and Drinking Patterns on Mortality From All Causes and Major Causes of Death in a Japanese Population. J Epidemiol, 28:140-148, 2018

58. Ugai T, Matsuo K, Oze I, Ito H, Wakai K, Wada K, Nagata C, Nakayama T, Liu R, Kitamura Y, Tamakoshi A, Tsuji I, Sugawara Y, Sawada N, Sadakane A, Tanaka K, Mizoue T, Inoue M, Tsugane S, Shimazu T. Smoking and subsequent risk of acute myeloid leukaemia: A pooled analysis of 9 cohort studies in Japan. Hematol Oncol, 36:262-268, 2018

59. Svensson T, Inoue M, Sawada N, Mimura M, Tsugane S. High serum total cholesterol is associated with suicide mortality in Japanese women independently of menopause. Acta Psychiatr Scand, 137:80-81, 2018

60. Kotemori A, Ishihara J, Zha L, Liu R, Sawada N, Iwasaki M, Sobue T, Tsugane S. Dietary acrylamide intake and risk of breast cancer: The Japan Public Health Center-based Prospective Study. Cancer Sci, 109:843-853, 2018

61. Lu Y, Sobue T, Kitamura T, Matsuse R, Kitamura Y, Matsuo K, Ito H, Oze I, Shimazu T, Yamaji T, Iwasaki M, Sasazuki S, Sawada N, Tsugane S. Cigarette smoking, alcohol drinking, and oral cavity and pharyngeal cancer in the Japanese: a population-based cohort study in Japan. Eur J Cancer Prev, 27:171-179, 2018

62. Charvat H, Sasazuki S, Shimazu T, Budhathoki S, Inoue M, Iwasaki M, Sawada N, Yamaji T, Tsugane S. Development of a risk prediction model for lung cancer: The Japan Public Health Center-based Prospective Study. Cancer Sci, 109:854-862, 2018

63. Katagiri R, Goto A, Budhathoki S, Yamaji T, Yamamoto H, Kato Y, Iwasaki M, Tsugane S. Association between plasma concentrations of branched-chain amino acids and adipokines in Japanese adults without diabetes. Sci Rep, 8:1043, 2018

64. Nojima M, Iwasaki M, Kasuga Y, Yokoyama S, Onuma H, Nishimura H, Kusama R, Yoshida T, Tsugane S. Correlation between global methylation level of peripheral blood leukocytes and serum C reactive protein level modified by MTHFR polymorphism: a cross-sectional study. BMC Cancer, 18:184, 2018

65. Budhathoki S, Hidaka A, Yamaji T, Sawada N, Tanaka-Mizuno S, Kuchiba A, Charvat H, Goto A, Kojima S, Sudo N, Shimazu T, Sasazuki S, Inoue M, Tsugane S, Iwasaki M. Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort. BMJ, 360:k671, 2018