Division of Prevention

Shizuka Sasazuki, Taichi Shimazu, Michihiro Mutoh, Charvat Hadrien, Nagisa Mori, Miho Nozue, Shingo Miyamoto, Manami Inoue, Yingyan Gong, Eiko Saito, Issei Ezawa, Md.Shafiur Rahman, Ruri Nakanishi, Masami Sakano

Introduction

The Division of Prevention has planned and conducted independent and collaborative studies on cancer prevention, with a special focus on environmental, lifestyle factors and biomarkers. Several epidemiological projects are currently in progress.

Our team and what we do

Our division focuses on prevention researches to investigate and develop prevention methods (lifestyle, chemoprevention, molecular marker, etc.), risk prediction, risk stratification models, and evidence-based cancer prevention guidelines.

Research activities

1.Evaluation of cancer prevention strategies in Japan and cancer prevention guidelines

To develop an evidence-based cancer prevention strategy in Japan, a systematic review of epidemiological research was conducted. The strength of evidence was evaluated in a manner similar to that used in the WHO/FAO Expert Consultation Report, in which evidence was classified as 'convincing', 'probable', 'possible', and 'insufficient'. Through this method, passive smoking was evaluated to have 'convincing'and 'possible'effect on increasing the risk of lung cancer and breast cancer, respectively. A web-based tool to predict the 10-year risk of developing gastric cancer based on the combination of H. pylori infection and atrophic gastritis status, so called 'ABC method', and lifestyle factors was constructed and released to the press to be more widely used (Figure 1). A pooled analysis of Japanese cohort studies was conducted and we found that the pooled analysis do not support the possible inverse association between fruit and vegetable consumption, and overall cancers in the Japanese population. The Asia Cohort Consortium (ACC) is a collaborative effort seeking to understand the relationship between genetics, environmental exposure, and the etiology of disease through the establishment of a cohort of at least one million healthy people throughout Asian countries. The ACC Coordinating Center was established at the Fred Hutchinson Cancer Research Center (Seattle, USA) and moved to our division in 2014. The data analysis system on-site and via remote access is now established, and several projects are ongoing.

2.Population-based Prospective Study (the JPHC study and the JPHC-NEXT Study) (primarily the development of preventive measures such as risk prediction; searching for chemoprevention candidates)

Ten-year cumulative probability of lung cancer occurrence estimates were calculated based on age, gender, and smoking-related factors taking into account the competing risk of death from other causes in the JPHC Study. This model might be used to encourage high-risk individuals to quit smoking and undergo screening. The association between cruciferous vegetables and lung cancer along with soy food and blood pressure were also analyzed.

Clinical trials

1.Development of prevention measures based on interventional research

We started a double-blind, randomized clinical trial of aspirin and mesalazine to see if these drugs suppress the occurrence of new adenomas in patients with a history of multiple colorectal adenomas. Another clinical research project aiming to develop colorectal cancer chemopreventive drugs is currently in progress.

Education

We have provided lectures on statistics, and supervised the research of one college student and a visiting research scholar.

Future prospects

We focus on research for the development of effective cancer prevention strategies. In addition to current established evidence, new perspectives such as biomarkers from blood and tumor tissues will be incorporated. This approach may lead to more accurate cancer prevention strategies by risk stratification. Furthermore, research aimed to search for an effective tool to support behavior modification for promoting health will be planned.

List of papers published in 2016

Journal

1.Hori M, Onaya H, Hiraoka N, Yamaji T, Kobayashi H, Takahashi M, Mutoh M, Shimada K, Nakagama H. Evaluation of the degree of pancreatic fatty infiltration by area-based assessment of CT images: comparison with histopathology-based and CT attenuation index-based assessments. Jpn J Radiol, 34:667-676, 2016

2.Ishikawa H, Mutoh M, Iwama T, Suzuki S, Abe T, Takeuchi Y, Nakamura T, Ezoe Y, Fujii G, Wakabayashi K, Nakajima T, Sakai T. Endoscopic management of familial adenomatous polyposis in patients refusing colectomy. Endoscopy, 48:51-55, 2016

3.Nakamura T, Ishikawa H, Mutoh M, Wakabayashi K, Kawano A, Sakai T, Matsuura N. Coffee prevents proximal colorectal adenomas in Japanese men: a prospective cohort study. Eur J Cancer Prev, 25:388-394, 2016

4.Hamoya T, Fujii G, Miyamoto S, Takahashi M, Totsuka Y, Wakabayashi K, Toshima J, Mutoh M. Effects of NSAIDs on the risk factors of colorectal cancer: a mini review. Genes Environ, 38:6, 2016

5.Miyamoto S, Terasaki M, Ishigamori R, Fujii G, Mutoh M. Prospective targets for colon cancer prevention: from basic research, epidemiology and clinical trial. J Dig Cancer Rep, 4:64-76, 2016

6.Akter S, Kashino I, Mizoue T, Matsuo K, Ito H, Wakai K, Nagata C, Nakayama T, Sadakane A, Tanaka K, Tamakoshi A, Sugawara Y, Sawada N, Inoue M, Tsugane S, Sasazuki S. Coffee drinking and colorectal cancer risk: an evaluation based on a systematic review and meta-analysis among the Japanese population. Jpn J Clin Oncol, 46:781-787, 2016

7.Yokoyama Y, Takachi R, Ishihara J, Ishii Y, Sasazuki S, Sawada N, Shinozawa Y, Tanaka J, Kato E, Kitamura K, Nakamura K, Tsugane S. Validity of Short and Long Self-Administered Food Frequency Questionnaires in Ranking Dietary Intake in Middle-Aged and Elderly Japanese in the Japan Public Health Center-Based Prospective Study for the Next Generation (JPHC-NEXT) Protocol Area. J Epidemiol, 26:420-432, 2016

8.Kondo H, Soda M, Sawada N, Inoue M, Imaizumi Y, Miyazaki Y, Iwanaga M, Tanaka Y, Mizokami M, Tsugane S. Smoking is a risk factor for development of adult T-cell leukemia/lymphoma in Japanese human T-cell leukemia virus type-1 carriers. Cancer Causes Control, 27:1059-1066, 2016

9.Budhathoki S, Yamaji T, Iwasaki M, Sawada N, Shimazu T, Sasazuki S, Yoshida T, Tsugane S. Vitamin D Receptor Gene Polymorphism and the Risk of Colorectal Cancer: A Nested Case-Control Study. PLoS One, 11:e0164648, 2016

10.Svensson T, Yamaji T, Budhathoki S, Hidaka A, Iwasaki M, Sawada N, Inoue M, Sasazuki S, Shimazu T, Tsugane S. Alcohol consumption, genetic variants in the alcohol- and folate metabolic pathways and colorectal cancer risk: the JPHC Study. Sci Rep, 6:36607, 2016

11.Ogawa T, Sawada N, Iwasaki M, Budhathoki S, Hidaka A, Yamaji T, Shimazu T, Sasazuki S, Narita Y, Tsugane S. Coffee and green tea consumption in relation to brain tumor risk in a Japanese population. Int J Cancer, 139:2714-2721, 2016

12.Wang Z, Seow WJ, Shiraishi K, Hsiung CA, Matsuo K, Liu J, Chen K, Yamji T, Yang Y, Chang IS, Wu C, Hong Y-C, Burdett L, Wyatt K, Chung CC, Li SA, Yeager M, Hutchinson A, Hu W, Caporaso N, Landi MT, Chatterjee N, Song M, Fraumeni JF, Jr., Kohno T, Yokota J, Kunitoh H, Ashikawa K, Momozawa Y, Daigo Y, Mitsudomi T, Yatabe Y, Hida T, Hu Z, Dai J, Ma H, Jin G, Song B, Wang Z, Cheng S, Yin Z, Li X, Ren Y, Guan P, Chang J, Tan W, Chen C-J, Chang G-C, Tsai Y-H, Su W-C, Chen K-Y, Huang M-S, Chen Y-M, Zheng H, Li H, Cui P, Guo H, Xu P, Liu L, Iwasaki M, Shimazu T, Tsugane S, Zhu J, Jiang G, Fei K, Park JY, Kim YH, Sung JS, Park KH, Kim YT, Jung YJ, Kang CH, Park IK, Kim HN, Jeon H-S, Choi JE, Choi YY, Kim JH, Oh I-J, Kim Y-C, Sung SW, Kim JS, Yoon H-I, Kweon S-S, Shin M-H, Seow A, Chen Y, Lim W-Y, Liu J, Wong MP, Lee VHF, Bassig BA, Tucker M, Berndt SI, Chow W-H, Ji B-T, Wang J, Xu J, Sihoe ADL, Ho JCM, Chan JKC, Wang J-C, Lu D, Zhao X, Zhao Z, Wu J, Chen H, Jin L, Wei F, Wu G, An S-J, Zhang X-C, Su J, Wu Y-L, Gao Y-T, Xiang Y-B, He X, Li J, Zheng W, Shu X-O, Cai Q, Klein R, Pao W, Lawrence C, Hosgood HD, 3rd, Hsiao C-F, Chien L-H, Chen Y-H, Chen C-H, Wang W-C, Chen C-Y, Wang C-L, Yu C-J, Chen H-L, Su Y-C, Tsai F-Y, Chen Y-S, Li Y-J, Yang T-Y, Lin C-C, Yang P-C, Wu T, Lin D, Zhou B, Yu J, Shen H, Kubo M, Chanock SJ, Rothman N, Lan Q. Meta-analysis of genome-wide association studies identifies multiple lung cancer susceptibility loci in never-smoking Asian women. Hum Mol Genet, 25:620-629, 2016

13.Onuma W, Tomono S, Miyamoto S, Fujii G, Hamoya T, Fujimoto K, Miyoshi N, Fukai F, Wakabayashi K, Mutoh M. Irsogladine maleate, a gastric mucosal protectant, suppresses intestinal polyp development in Apc-mutant mice. Oncotarget, 7:8640-8652, 2016

14.Imaoka T, Nishimura M, Daino K, Morioka T, Nishimura Y, Uemura H, Akimoto K, Furukawa Y, Fukushi M, Wakabayashi K, Mutoh M, Shimada Y. A Rat Model to Study the Effects of Diet-Induced Obesity on Radiation-Induced Mammary Carcinogenesis. Radiat Res, 185:505-515, 2016

15.Cai H, Ye F, Michel A, Murphy G, Sasazuki S, Taylor PR, Qiao Y-L, Park SK, Yoo K-Y, Jee SH, Cho ER, Kim J, Chen S-C, Abnet CC, Tsugane S, Cai Q, Shu X-O, Zheng W, Pawlita M, Epplein M. Helicobacter pylori blood biomarker for gastric cancer risk in East Asia. Int J Epidemiol, 45:774-781, 2016

16.Charvat H, Remontet L, Bossard N, Roche L, Dejardin O, Rachet B, Launoy G, Belot A. A multilevel excess hazard model to estimate net survival on hierarchical data allowing for non-linear and non-proportional effects of covariates. Stat Med, 35:3066-3084, 2016

17.Hori M, Tanaka H, Wakai K, Sasazuki S, Katanoda K. Secondhand smoke exposure and risk of lung cancer in Japan: a systematic review and meta-analysis of epidemiologic studies. Jpn J Clin Oncol, 46:942-951, 2016

18.Inoki K, Nakajima T, Sekine S, Sugano K, Tsukamoto S, Yamada M, Mutoh M, Sakamoto T, Matsuda T, Sekiguchi M, Ushiama M, Yoshida T, Sakamoto H, Kanemitsu Y, Saito Y. Depressed-type submucosal invasive colorectal cancer in a patient with Lynch syndrome diagnosed using short-interval colonoscopy. Dig Endosc, 28:749-754, 2016

19.Hori M, Mutoh M, Imai T, Nakagama H, Takahashi M. Possible involvement of pancreatic fatty infiltration in pancreatic carcinogenesis. JOP, 17:166-175, 2016

20.Jung S, Wang M, Anderson K, Baglietto L, Bergkvist L, Bernstein L, van den Brandt PA, Brinton L, Buring JE, Heather Eliassen A, Falk R, Gapstur SM, Giles GG, Goodman G, Hoffman-Bolton J, Horn-Ross PL, Inoue M, Kolonel LN, Krogh V, Lof M, Maas P, Miller AB, Neuhouser ML, Park Y, Robien K, Rohan TE, Scarmo S, Schouten LJ, Sieri S, Stevens VL, Tsugane S, Visvanathan K, Wilkens LR, Wolk A, Weiderpass E, Willett WC, Zeleniuch-Jacquotte A, Zhang SM, Zhang X, Ziegler RG, Smith-Warner SA. Alcohol consumption and breast cancer risk by estrogen receptor status: in a pooled analysis of 20 studies. Int J Epidemiol, 45:916-928, 2016

21.Kabeya Y, Goto A, Kato M, Matsushita Y, Takahashi Y, Isogawa A, Inoue M, Mizoue T, Tsugane S, Kadowaki T, Noda M. Time spent walking and risk of diabetes in japanese adults: The Japan Public Health Center-Based Prospective Diabetes Study. J Epidemiol, 26:224-232, 2016

22.Wu K, Spiegelman D, Hou T, Albanes D, Allen NE, Berndt SI, van den Brandt PA, Giles GG, Giovannucci E, Alexandra Goldbohm R, Goodman GG, Goodman PJ, Hakansson N, Inoue M, Key TJ, Kolonel LN, Mannisto S, McCullough ML, Neuhouser ML, Park Y, Platz EA, Schenk JM, Sinha R, Stampfer MJ, Stevens VL, Tsugane S, Visvanathan K, Wilkens LR, Wolk A, Ziegler RG, Smith-Warner SA. Associations between unprocessed red and processed meat, poultry, seafood and egg intake and the risk of prostate cancer: A pooled analysis of 15 prospective cohort studies. Int J Cancer, 138:2368-2382, 2016

23.Mori G, Nakajima T, Asada K, Shimazu T, Yamamichi N, Maekita T, Yokoi C, Fujishiro M, Gotoda T, Ichinose M, Ushijima T, Oda I. Incidence of and risk factors for metachronous gastric cancer after endoscopic resection and successful Helicobacter pylori eradication: results of a large-scale, multicenter cohort study in Japan. Gastric Cancer, 19:911-918, 2016

24.Charvat H, Sasazuki S, Inoue M, Iwasaki M, Sawada N, Shimazu T, Yamaji T, Tsugane S. Prediction of the 10-year probability of gastric cancer occurrence in the Japanese population: the JPHC study cohort II. Int J Cancer, 138:320-331, 2016

25.Iwasaki M, Ishihara J, Takachi R, Todoriki H, Yamamoto H, Miyano H, Yamaji T, Tsugane S. Validity of a Self-Administered Food-Frequency Questionnaire for Assessing Amino Acid Intake in Japan: Comparison With Intake From 4-Day Weighed Dietary Records and Plasma Levels. J Epidemiol, 26:36-44, 2016

26.Makiuchi T, Sobue T, Kitamura T, Ishihara J, Sawada N, Iwasaki M, Sasazuki S, Yamaji T, Shimazu T, Tsugane S. Association between green tea/coffee consumption and biliary tract cancer: A population-based cohort study in Japan. Cancer Sci, 107:76-83, 2016

27.Svensson T, Inoue M, Sawada N, Charvat H, Iwasaki M, Sasazuki S, Shimazu T, Yamaji T, Kawamura N, Shibuya K, Mimura M, Tsugane S. Coping strategies and cancer incidence and mortality: The Japan Public Health Center-based prospective study. Cancer Epidemiol, 40:126-133, 2016

28.Krull Abe S, Inoue M, Sawada N, Iwasaki M, Shimazu T, Yamaji T, Sasazuki S, Saito E, Tanaka Y, Mizokami M, Tsugane S. Hepatitis B and C Virus Infection and Risk of Pancreatic Cancer: A Population-Based Cohort Study (JPHC Study Cohort II). Cancer Epidemiol Biomarkers Prev, 25:555-557, 2016

29.Kurotani K, Akter S, Kashino I, Goto A, Mizoue T, Noda M, Sasazuki S, Sawada N, Tsugane S. Quality of diet and mortality among Japanese men and women: Japan Public Health Center based prospective study. BMJ, 352:i1209, 2016

30.Masaoka H, Matsuo K, Ito H, Wakai K, Nagata C, Nakayama T, Sadakane A, Tanaka K, Tamakoshi A, Sugawara Y, Mizoue T, Sawada N, Inoue M, Tsugane S, Sasazuki S. Cigarette smoking and bladder cancer risk: an evaluation based on a systematic review of epidemiologic evidence in the Japanese population. Jpn J Clin Oncol, 46:273-283, 2016

31.Svensson T, Inoue M, Sawada N, Yamagishi K, Charvat H, Saito I, Kokubo Y, Iso H, Kawamura N, Shibuya K, Mimura M, Tsugane S. Coping strategies and risk of cardiovascular disease incidence and mortality: the Japan Public Health Center-based prospective Study. Eur Heart J, 37:890-899, 2016

32.Abe SK, Inoue M, Sawada N, Ishihara J, Iwasaki M, Yamaji T, Shimazu T, Sasazuki S, Tsugane S. Glycemic index and glycemic load and risk of colorectal cancer: a population-based cohort study (JPHC Study). Cancer Causes Control, 27:583-593, 2016

33.Goto A, Noda M, Sawada N, Kato M, Hidaka A, Mizoue T, Shimazu T, Yamaji T, Iwasaki M, Sasazuki S, Inoue M, Kadowaki T, Tsugane S. High hemoglobin A1c levels within the non-diabetic range are associated with the risk of all cancers. Int J Cancer, 138:1741-1753, 2016

34.Honjo K, Iso H, Ikeda A, Inoue M, Sawada N, Tsugane S. Marital Transition and Risk of Stroke: How Living Arrangement and Employment Status Modify Associations. Stroke, 47:991-998, 2016

35.Saito E, Charvat H, Goto A, Matsuda T, Noda M, Sasazuki S, Inoue M. Burden of cancer associated with type 2 diabetes mellitus in Japan, 2010-2030. Cancer Sci, 107:521-527, 2016

36.Cui R, Iso H, Yamagishi K, Saito I, Kokubo Y, Inoue M, Sawada N, Tsugane S. Trends in the proportions of stroke subtypes and coronary heart disease in the Japanese men and women from 1995 to 2009. Atherosclerosis, 248:219-223, 2016

37.Shin S, Saito E, Inoue M, Sawada N, Ishihara J, Takachi R, Nanri A, Shimazu T, Yamaji T, Iwasaki M, Sasazuki S, Tsugane S. Dietary pattern and breast cancer risk in Japanese women: the Japan Public Health Center-based Prospective Study (JPHC Study). Br J Nutr, 115:1769-1779, 2016

38.Yatsuya H, Iso H, Li Y, Yamagishi K, Kokubo Y, Saito I, Sawada N, Inoue M, Tsugane S. Development of a Risk Equation for the Incidence of Coronary Artery Disease and Ischemic Stroke for Middle-Aged Japanese- Japan Public Health Center-Based Prospective Study. Circ J, 80:1386-1395, 2016

39.Koyanagi YN, Matsuo K, Ito H, Wakai K, Nagata C, Nakayama T, Sadakane A, Tanaka K, Tamakoshi A, Sugawara Y, Mizoue T, Sawada N, Inoue M, Tsugane S, Sasazuki S, Iwasaki M, Otani T, Shimazu T, Yamaji T, Tsuji I, Tsubono Y, Nishino Y. Cigarette smoking and the risk of head and neck cancer in the Japanese population: a systematic review and meta-analysis. Jpn J Clin Oncol, 46:580-595, 2016

40.Hidaka A, Sasazuki S, Matsuo K, Ito H, Charvat H, Sawada N, Shimazu T, Yamaji T, Iwasaki M, Inoue M, Tsugane S. CYP1A1, GSTM1 and GSTT1 genetic polymorphisms and gastric cancer risk among Japanese: A nested case-control study within a large-scale population-based prospective study. Int J Cancer, 139:759-768, 2016