Annual Report 2024
Division of Epidemiology
Motoki Iwasaki, Taiki Yamaji, Shiori Nakano, Maki Igarashi, Yoko Shimizu, Akiko Hanyuda, Kenshiro Nishihara, Yuki Honma
Introduction
Epidemiological research aims to build evidence for cancer prevention by identifying the causes of cancer in humans through large-scale cohort and other population-based studies.
Research Activities
1) Utilization of Biorepository Samples for the Epidemiological Research
To establish an infrastructure for molecular pathological epidemiology research, we initiated the collection of tumor tissue samples from participants in the Yokote area of the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT study). In 2024, we successfully collected tumor tissue samples from approximately 100 cases each of colorectal and gastric cancer. At the same time, in preparation for further case collection and expansion to other regions, we are exploring region-specific strategies for tumor tissue acquisition.
2) Epidemiological Research on Cancer Etiology and Prevention
We examined the associations of the oxidative stress biomarker, derivatives of reactive oxygen metabolites (d-ROMs), and the antioxidant biomarker, biological antioxidant potential (BAP), with overall cancer incidence as well as site-specific cancer incidence. An increased risk of hepatocellular carcinoma and lung cancer was observed in the group with higher d-ROM levels, while a decreased risk of gastric cancer was observed in the group with higher BAP levels.
Whole-genome sequencing was conducted on cancer patients in their 40s and 50s identified through the JPHC-NEXT Study. Germline single-nucleotide variants in cancer-related genes were observed in approximately 40% of breast cancer cases. To estimate cancer risk in the general population, a case–cohort study of breast cancer was constructed, and whole-exome sequencing was performed on the subcohort.
We have conducted molecular pathological epidemiology research to investigate the causes and prevention of cancer, utilizing biological samples collected in the Japan Public Health Center-based Prospective Study (JPHC study). First, we examined the association between vitamin D intake and colorectal cancer risk according to vitamin D receptor (VDR) expression levels. A protective effect of vitamin D was observed only in colorectal cancers with high VDR expression in the tumor stroma. Second, we evaluated the associations of height, weight, and physical activity with colorectal cancer risk according to insulin receptor expression levels. Our findings suggest that the effects of height, weight, and physical activity on colorectal carcinogenesis or its suppression may involve pathways other than those mediated by the insulin receptor. These two studies were published in international peer-reviewed journals.
3) Consortium on Large-scale Molecular Epidemiological Studies in Japan and International Collaborations
By utilizing data from the Japanese Consortium of Genetic Epidemiology, we published a genome-wide association study in an international peer-reviewed journal, identifying CD36 as a gene associated with kidney function traits. In the context of international collaborative research, we co-authored several manuscripts on genetic studies as members of international consortia focusing on lung, colorectal, and breast cancer.
Education
We supervised the research of five graduate students and one of them obtained their Ph.D.
Future Prospects
We aim to further expand our research infrastructure for epidemiological studies that will be highly acclaimed internationally and, through its utilization, develop evidence that contributes to the personalized prevention of cancer.
List of papers published in 2024
Journal
1. Tanitame M, Inoue M, Yamaji T, Iwasaki M, Tsugane S, Sawada N. Cigarette Smoking, Alcohol Consumption, and the Risk of Thyroid Cancer in Japan: The Japan Public Health Center-Based Prospective Study. Cancer epidemiology, biomarkers & prevention, 34:317-323, 2025
2. Takachi R, Yamagishi M, Goto A, Inoue M, Yamaji T, Iwasaki M, Yamagishi K, Iso H, Tsugane S, Sawada N. Consumption of Sodium and Its Ratio to Potassium in Relation to All-Cause, Cause-Specific, and Premature Noncommunicable Disease Mortality in Middle-Aged Japanese Adults: A Prospective Cohort Study. The Journal of nutrition, 155:945-956, 2025
3. Jia G, Chen Z, Ping J, Cai Q, Tao R, Li C, Bauer JA, Xie Y, Ambs S, Barnard ME, Chen Y, Choi JY, Gao YT, Garcia-Closas M, Gu J, Hu JJ, Iwasaki M, John EM, Kweon SS, Li CI, Matsuda K, Matsuo K, Nathanson KL, Nemesure B, Olopade OI, Pal T, Park SK, Park B, Press MF, Sanderson M, Sandler DP, Shen CY, Troester MA, Yao S, Zheng Y, Ahearn T, Brewster AM, Falusi A, Hennis AJM, Ito H, Kubo M, Lee ES, Makumbi T, Ndom P, Noh DY, O'Brien KM, Ojengbede O, Olshan AF, Park MH, Reid S, Yamaji T, Zirpoli G, Butler EN, Huang M, Low SK, Obafunwa J, Weinberg CR, Zhang H, Zhao H, Cote ML, Ambrosone CB, Huo D, Li B, Kang D, Palmer JR, Shu XO, Haiman CA, Guo X, Long J, Zheng W. Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions. Nature genetics, 57:80-87, 2025
4. Inoue Y, Suzuki S, Sawada N, Morisaki N, Narita Z, Yamaji T, Kokubo Y, Doi T, Nishita Y, Iwasaki M, Inoue M, Mizoue T. Association between physical multimorbidity in middle adulthood and mortality: findings from two large cohort studies in Japan. BMC public health, 25:92, 2025
5. Omura T, Goto A, Nakayama I, Saito J, Noda M, Yasuda N, Saito I, Kato T, Arima K, Kawakami F, Sakata K, Tanno K, Yamaji T, Iwasaki M, Yamagishi K, Iso H, Inoue M, Tsugane S, Sawada N. Socioeconomic Status and Diabetes Prevalence in the Japanese: Insights From the JPHC-NEXT Study. Mayo Clinic proceedings, 100:452-464, 2025
6. Yamagishi M, Takachi R, Ishihara J, Shiraishi A, Kurotani K, Maruya S, Ishii Y, Kito K, Nakamura K, Tanaka J, Yamaji T, Iso H, Iwasaki M, Tsugane S, Sawada N. High adherence to a food guide may be associated with lower 24-h urinary sodium excretion and sodium-to-potassium ratio, and higher potassium excretion. Clinical nutrition ESPEN, 67:146-154, 2025
7. Takada N, Ishikawa M, Sato K, Kunikata H, Ninomiya T, Hanyuda A, Fukuda E, Yamaguchi K, Ono C, Kirihara T, Shintani C, Tsusu C, Osanai A, Goshima N, Izumi Y, Zorumski CF, Nakazawa T. Proteome-Wide Analysis of Autoantibodies in Open-Angle Glaucoma in Japanese Population: A Pilot Study. Biomedicines, 13:718, 2025
8. Itoh H, Harada KH, Hamada GS, Lyu Z, Fujitani T, Harada Sassa M, Yamaji T, Tsugane S, Iwasaki M. Plasma perfluoroalkyl substances and breast cancer risk in Brazilian women: a case-control study. Environmental health, 24:13, 2025
9. Igarashi M, Iwasaki M, Katagiri R, Tsugane S, Kobayashi N, Yamaji T. Sex difference in the association of dietary fiber intake with visceral fat volume in Japanese adults. European journal of nutrition, 63:1973-1981, 2024
10. Taguri M, Kuchiba A, Yamaji T, Sawada N, Goto A, Iwasaki M, Tsugane S. Importance of Circulating Leptin and Adiponectin in the Causal Pathways Between Obesity and the Development of Colorectal Cancer in Japanese Men. Journal of epidemiology, 34:563-569, 2024
11. Nakano S, Yamaji T, Hidaka A, Shimazu T, Shiraishi K, Kuchiba A, Saito M, Kunishima F, Nakaza R, Kohno T, Sawada N, Inoue M, Tsugane S, Iwasaki M. Dietary vitamin D intake and risk of colorectal cancer according to vitamin D receptor expression in tumors and their surrounding stroma. Journal of gastroenterology, 59:825-835, 2024
12. Nishihara K, Nakano S, Yamaji T, Goto A, Hidaka A, Shimazu T, Kuchiba A, Saito M, Kunishima F, Nakaza R, Kato I, Sawada N, Inoue M, Tsugane S, Iwasaki M. Height, body mass index, physical activity, and risk of colorectal cancer in relation to expression of insulin receptor: The Japan Public Health Center-based Prospective Study. International journal of cancer, 155:1751-1761, 2024
13. Yoshii K, Morisaki N, Piedvache A, Nakada S, Arima K, Aoyagi K, Nakashima H, Yasuda N, Muraki I, Yamagishi K, Saito I, Kato T, Tanno K, Yamaji T, Iwasaki M, Inoue M, Tsugane S, Sawada N. Association Between Birth Weight and Prevalence of Cardiovascular Disease and Other Lifestyle-related Diseases Among the Japanese Population: The JPHC-NEXT Study. Journal of epidemiology, 34:307-315, 2024
14. Hishida A, Nakatochi M, Sutoh Y, Nakano S, Momozawa Y, Narita A, Tanno K, Shimizu A, Hozawa A, Kinoshita K, Yamaji T, Goto A, Noda M, Sawada N, Ikezaki H, Nagayoshi M, Hara M, Suzuki S, Koyama T, Koriyama C, Katsuura-Kamano S, Kadota A, Kuriki K, Yamamoto M, Sasaki M, Iwasaki M, Matsuo K, Wakai K. GWAS Meta-analysis of Kidney Function Traits in Japanese Populations. Journal of epidemiology, 34:526-534, 2024
15. Chen Z, Guo X, Tao R, Huyghe JR, Law PJ, Fernandez-Rozadilla C, Ping J, Jia G, Long J, Li C, Shen Q, Xie Y, Timofeeva MN, Thomas M, Schmit SL, Díez-Obrero V, Devall M, Moratalla-Navarro F, Fernandez-Tajes J, Palles C, Sherwood K, Briggs SEW, Svinti V, Donnelly K, Farrington SM, Blackmur J, Vaughan-Shaw PG, Shu XO, Lu Y, Broderick P, Studd J, Harrison TA, Conti DV, Schumacher FR, Melas M, Rennert G, Obón-Santacana M, Martín-Sánchez V, Oh JH, Kim J, Jee SH, Jung KJ, Kweon SS, Shin MH, Shin A, Ahn YO, Kim DH, Oze I, Wen W, Matsuo K, Matsuda K, Tanikawa C, Ren Z, Gao YT, Jia WH, Hopper JL, Jenkins MA, Win AK, Pai RK, Figueiredo JC, Haile RW, Gallinger S, Woods MO, Newcomb PA, Duggan D, Cheadle JP, Kaplan R, Kerr R, Kerr D, Kirac I, Böhm J, Mecklin JP, Jousilahti P, Knekt P, Aaltonen LA, Rissanen H, Pukkala E, Eriksson JG, Cajuso T, Hänninen U, Kondelin J, Palin K, Tanskanen T, et al. (複数名のため一部抜粋して記載。詳細は掲載先をご参照ください). Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes. Nature communications, 15:3557, 2024
16. Yamagishi M, Takachi R, Ishihara J, Maruya S, Ishii Y, Kito K, Nakamura K, Tanaka J, Yamaji T, Iso H, Iwasaki M, Tsugane S, Sawada N. Development and preliminary validation of a prediction formula of sodium and sodium-to-potassium ratio based on multiple regression using 24-h urines. Scientific reports, 14:9704, 2024
17. Narita Z, Hidese S, Kanehara R, Tachimori H, Hori H, Kim Y, Kunugi H, Arima K, Mizukami S, Tanno K, Takanashi N, Yamagishi K, Muraki I, Yasuda N, Saito I, Maruyama K, Yamaji T, Iwasaki M, Inoue M, Tsugane S, Sawada N. Association of sugary drinks, carbonated beverages, vegetable and fruit juices, sweetened and black coffee, and green tea with subsequent depression: A five-year cohort study. Clinical nutrition (Edinburgh, Scotland), 43:1395-1404, 2024
18. Hirabayashi M, Wilunda C, Murai U, Yamaji T, Iwasaki M, Inoue M, Tsugane S, Sawada N. Association between fish and shellfish consumption, n-3 polyunsaturated fatty acids, and gastric cancer risk: the Japan Public Health Center-based Prospective Study. European journal of nutrition, 63:1529-1544, 2024
19. Funakoshi Y, Maruyama K, Kato T, Saito I, Takanashi N, Tanno K, Yamagishi K, Muraki I, Yasuda N, Arima K, Nakashima H, Yamaji T, Iwasaki M, Inoue M, Tsugane S, Sawada N. Association of depressive symptoms with incident fractures: the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT). Osteoporosis international, 35:1261-1271, 2024
20. Kanehara R, Park SY, Okada Y, Iwasaki M, Tsugane S, Sawada N, Inoue M, Haiman CA, Wilkens LR, Le Marchand L. Intake of Sugar and Food Sources of Sugar and Colorectal Cancer Risk in the Multiethnic Cohort Study. The Journal of nutrition, 154:2481-2492, 2024
21. Ihira H, Nakano S, Yamaji T, Katagiri R, Sawada N, Inoue M, Tsugane S, Iwasaki M. Plasma albumin, bilirubin, and uric acid and the subsequent risk of cancer: a case-cohort study in the Japan Public Health Center-based Prospective Study. American journal of epidemiology, 193:1460-1469, 2024
22. Hanyuda A, Kubota M, Kubota S, Masui S, Yuki K, Ayaki M, Negishi K. Establishing the cutoff value of near visual acuity for assessment of early presbyopia. Japanese journal of ophthalmology, 68:709-716, 2024
23. Hanyuda A, Raita Y, Ninomiya T, Hashimoto K, Takada N, Sato K, Inoue J, Koshiba S, Tamiya G, Narita A, Akiyama M, Omodaka K, Tsuda S, Yokoyama Y, Himori N, Yamamoto Y, Taniguchi T, Negishi K, Nakazawa T. Metabolomic Profiling of Open-Angle Glaucoma Etiologic Endotypes: Tohoku Multi-Omics Glaucoma Study. Investigative ophthalmology & visual science, 65:44, 2024
24. Shimizu Y, Yamaji T, Inoue M, Yasuda N, Yamagishi K, Sawada N, Tsugane S, Iwasaki M. Plasma uric acid levels and risk of dementia in a population-based cohort study. Journal of the neurological sciences, 467:123323, 2024