Division of Epidemiology

Motoki Iwasaki, Norie Sawada, Taiki Yamaji, Atsushi Goto, Izumi Mishiro, Akihisa Hidaka, Sanjeev Budhathoki, Masanori Goto, Kayo Ohashi, Jun Umesawa, Ari Nakamura, Tsuyuka Ohtsuki, Sangah Shin, Ayaka Sunami, Hikaru Ihira, Rieko Kanehara, Aya Morishita

Introduction

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

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 the studies for relatively rare cancer, increased consumption of vegetables and fruits was significantly associated with a decreased risk of extrahepatic bile duct cancer (Hazard ratio [HR] = 0.49 for total vegetables and fruits, HR = 0.55 for total vegetables, and HR = 0.60 for green vegetables). We found a significant inverse association between coffee consumption and brain tumor risk (≥3 cups/day; HR = 0.47, 95%CI = 0.22-0.98).

Baseline survey for the JPHC study for the NEXT generation (JPHC-NEXT) completed by the end of 2016, and we obtained questionnaire information from 115,163 participants, and biological samples and information from 55,733 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 through means such as omics data analysis

In the nested case-control study for colorectal cancer within the JPHC study, we investigated associations between genetic polymorphisms of enzymes in the alcohol- and folate metabolic pathways, and colorectal cancer risk. When compared to the CC genotype, the MTHFR rs1801133 CT/TT genotype was inversely associated with colorectal cancer (OR = 0.72, 95% CI, 0.54-0.97). In the analysis of 29 vitamin D receptor SNPs, eight SNPs, namely rs2254210, rs1540339, rs2107301, rs11168267, rs11574113, rs731236, rs3847987 and rs11574143, the latter five of which were located in the 3'region, were nominally associated with the risk of colorectal cancer (P = 0.01-0.048).

In order to develop a risk prediction model for cancer among Japanese people using information on genetic factors and plasma biomarkers in addition to lifestyle factors, we have conducted a case-cohort study of total cancer within the baseline survey of the JPHC study and performed data analysis.

Education

Supervised the research of three research resident fellowships.

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. Progress of the JPHC for the NEXT generation (JPHC-NEXT)

List of papers published in 2016

Journal

1.Yoneyama T, Ohtsuki S, Honda K, Kobayashi M, Iwasaki M, Uchida Y, Okusaka T, Nakamori S, Shimahara M, Ueno T, Tsuchida A, Sata N, Ioka T, Yasunami Y, Kosuge T, Kaneda T, Kato T, Yagihara K, Fujita S, Huang W, Yamada T, Tachikawa M, Terasaki T. Identification of IGFBP2 and IGFBP3 As Compensatory Biomarkers for CA19-9 in Early-Stage Pancreatic Cancer Using a Combination of Antibody-Based and LC-MS/MS-Based Proteomics. PLoS One, 11:e0161009, 2016

2.Taira N, Arai M, Ikeda M, Iwasaki M, Okamura H, Takamatsu K, Nomura T, Yamamoto S, Ito Y, Mukai H. The Japanese Breast Cancer Society clinical practice guidelines for epidemiology and prevention of breast cancer, 2015 edition. Breast Cancer, 23:343-356, 2016

3.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

4.Iwasaki M, Le Marchand L, Franke AA, Hamada GS, Miyajima NT, Sharma S, Yamaji T, Tsugane S. Comparison of plasma levels of obesity-related biomarkers among Japanese populations in Tokyo, Japan, Sao Paulo, Brazil, and Hawaii, USA. Eur J Cancer Prev, 25:41-49, 2016

5.Shiwa Y, Hachiya T, Furukawa R, Ohmomo H, Ono K, Kudo H, Hata J, Hozawa A, Iwasaki M, Matsuda K, Minegishi N, Satoh M, Tanno K, Yamaji T, Wakai K, Hitomi J, Kiyohara Y, Kubo M, Tanaka H, Tsugane S, Yamamoto M, Sobue K, Shimizu A. Adjustment of Cell-Type Composition Minimizes Systematic Bias in Blood DNA Methylation Profiles Derived by DNA Collection Protocols. PLoS One, 11:e0147519, 2016

6.Kubota Y, Iso H, Sawada N, Tsugane S. Association of Breakfast Intake With Incident Stroke and Coronary Heart Disease: The Japan Public Health Center-Based Study. Stroke, 47:477-481, 2016

7.Pandey JP, Gao G, Namboodiri AM, Iwasaki M, Kasuga Y, Hamada GS, Tsugane S. Humoral Immunity to Cytomegalovirus Glycoprotein B in Patients With Breast Cancer and Matched Controls: Contribution of Immunoglobulin gamma, kappa, and Fcgamma Receptor Genes. J Infect Dis, 213:611-617, 2016

8.Akter S, Kurotani K, Kashino I, Goto A, Mizoue T, Noda M, Sawada N, Tsugane S. High Dietary Acid Load Score Is Associated with Increased Risk of Type 2 Diabetes in Japanese Men: The Japan Public Health Center-based Prospective Study. J Nutr, 146:1076-1083, 2016

9.Kimura T, Iso H, Honjo K, Ikehara S, Sawada N, Iwasaki M, Tsugane S. Educational Levels and Risk of Suicide in Japan: The Japan Public Health Center Study (JPHC) Cohort I. J Epidemiol, 26:315-321, 2016

10.Yamauchi T, Inagaki M, Yonemoto N, Iwasaki M, Akechi T, Sawada N, Iso H, Noda M, Tsugane S. History of diabetes and risk of suicide and accidental death in Japan: The Japan Public Health Centre-based Prospective Study, 1990-2012. Diabetes Metab, 42:184-191, 2016

11.Kakinuma R, Noguchi M, Ashizawa K, Kuriyama K, Maeshima AM, Koizumi N, Kondo T, Matsuguma H, Nitta N, Ohmatsu H, Okami J, Suehisa H, Yamaji T, Kodama K, Mori K, Yamada K, Matsuno Y, Murayama S, Murata K. Natural History of Pulmonary Subsolid Nodules: A Prospective Multicenter Study. J Thorac Oncol, 11:1012-1028, 2016

12.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

13.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

14.Han M-R, Long J, Choi J-Y, Low S-K, Kweon S-S, Zheng Y, Cai Q, Shi J, Guo X, Matsuo K, Iwasaki M, Shen C-Y, Kim MK, Wen W, Li B, Takahashi A, Shin M-H, Xiang Y-B, Ito H, Kasuga Y, Noh D-Y, Matsuda K, Park MH, Gao Y-T, Iwata H, Tsugane S, Park SK, Kubo M, Shu X-O, Kang D, Zheng W. Genome-wide association study in East Asians identifies two novel breast cancer susceptibility loci. Hum Mol Genet, 25:3361-3371, 2016

15.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

16.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

17.Mishiro I, Sawada N, Iwasaki M, Ohashi K, Tsugane S. Minimum Cost Estimation of a Baseline Survey for a Molecular Epidemiology Cohort Study: Collecting Participants in a Model Region in Japan. J Epidemiol, 26:522-529, 2016

18.Saito I, Yamagishi K, Kokubo Y, Yatsuya H, Iso H, Sawada N, Inoue M, Tsugane S. Association between mortality and incidence rates of coronary heart disease and stroke: The Japan Public Health Center-based prospective (JPHC) study. Int J Cardiol, 222:281-286, 2016

19.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

20.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

21.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

22.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

23.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

24.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

25.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

26.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

27.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

28.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

29.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

30.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

31.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

32.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

33.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

34.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

35.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

36.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

37.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