The JPHC Study: Design and Some Findings on the Typical Japanese Diet

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1 Review Article Jpn J Clin Oncol 2014;44(9) doi: /jjco/hyu096 Advance Access Publication 7 August 2014 The JPHC Study: Design and Some Findings on the Typical Japanese Diet Shoichiro Tsugane * and Norie Sawada Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan *For reprints and all correspondence: Shoichiro Tsugane, Research Center for Cancer Prevention and Screening, National Cancer Center, Tsukiji, Chuo-ku, Tokyo , Japan. stsugane@ncc.go.jp Received May 21, 2014; accepted July 1, 2014 The Japan Public Health Center-based prospective Study conducted a baseline survey for registered residents aged years within 11 public health center areas nationwide in Five- and 10-year follow-up surveys were conducted to update information on lifestyle habits and health conditions. In total, participants responded to at least one of the three questionnaire surveys, and to all three. In addition, participants provided blood samples on at least one of the two sampling times, and on both. The subjects have been followed for vital status and the occurrence of cancer and other diseases. As of December 2011, deaths have been documented, as well as cases of cancer, 6000 cases of stroke and 1100 cases of myocardial infarction. We have tested the association between potential causal factors and the incidence of or mortality from cancer and other diseases, and published.250 papers to date. Typical dietary habits in Japan are high consumption of soy/isoflavones, fish/n-3 fatty acids, salt/salted foods and green tea, and low consumption of red meat and saturated fat. This paper briefly summarizes the observed associations of these foods/nutrients with cancer, cardiovascular diseases and diabetes. The Japan Public Health Center-based prospective Study is scheduled to conduct active follow-up for a total of 30 years, and we plan to publish additional evidence on the potential causes of a shorter life and major disease occurrence. Key words: epidemiol-prevention JPHC Study typical diet THE JAPAN PUBLIC HEALTH CENTER-BASED PROSPECTIVE STUDY (JPHC STUDY) The JPHC Study conducted a baseline survey of registered residents aged years within 11 public health center areas nationwide from (Fig. 1). The questionnaire was distributed mostly by hand. Approximately people returned the questionnaire, giving a response rate of 81%, and provided blood samples or health checkup data, which most providing both. The 5- and 10-year followup surveys were conducted to update information on lifestyle habits and health conditions. Approximately people returned the questionnaire at 5 years and at 10 years. Among responders to the baseline questionnaire, (80%) returned the questionnaire at 5 years and (76%) at 10 years. In total, (93%) participants responded to at least one of the three questionnaire surveys, and (55%) participated in all three. In addition, (43%) participants provided blood samples on at least one of the two sampling times, and (17%) provided blood samples at both times. Numbers of participants at each survey are summarized in Table 1. A 15-year follow-up questionnaire survey was conducted to follow-up the occurrence of several diseases by mail only, but response was received from only (response rate 43.6%). The subjects have been followed for their vital status and the occurrence of cancer and other diseases, and are scheduled to be followed for a total of 30 years (Fig. 2). As of December 2011, deaths have been documented, with the major # The Author Published by Oxford University Press. All rights reserved. For Permissions, please journals.permissions@oup.com

2 778 JPHC Study: design and some findings Figure 1. Map of the Japan Public Health Center-based prospective Study area. Table 1. Number of participants at each survey Subjects N ¼ *217 subjects were notified as ineligible during follow-up Baseline 5-year follow-up 10-year follow-up Either All N % N % N % N % N % Questionnaire Blood samples Health checkup data causes being cancer (38%), heart disease (13%) and stroke (10%) (Fig. 3). Among cancer, lung cancer (19%) was the most frequent, followed by stomach (15%), liver (12%), colorectum (11%) and pancreas (7%). In stark contrast to western populations, ischemic heart disease accounted for only 6% of all deaths cases of cancer, 6000 cases of stroke and 1100 cases of myocardial infarction were documented. The most frequent cancer was colorectum (20%), followed by stomach (19%), lung (12%), liver (6%), breast (6%) and prostate (6%) (Fig. 4). Strengths of the JPHC Study include: (i) its large scale, with coverage of areas throughout Japan; (ii) population-based cohort with over 80% response rate; (iii) use of validated questionnaires (three times), including a comprehensive food frequency questionnaire (FFQ) and physical activity questionnaire (PAQ); (iv) availability of blood samples (two times), including DNA, and health checkup data (two times); (v) almost complete follow-up for vital status and cause of death (in decedents) among all subjects (over 98% during 20 years); and (vi) active follow-up for incidence of cancer, stroke and myocardial infarction among subjects in the study area. In contrast, weaknesses include: (i) coverage mainly restricted to rural areas; (ii) limited age range (40 69 years); (iii) exposure assessment repeated only 2 4 times and no information after 10 or 15 years; (iv) blood samples for only half of the subjects; and (v) no follow-up for incidence of cancer, stroke or myocardial infarction among subjects outside the study area ( 20% at around 20 years). We have tested associations between potential causal factors and the incidence of or mortality from cancer and other diseases, and to date have published.250 papers. SELECTED FINDINGS ON THE TYPICAL JAPANESE DIET Findings on the typical Japanese diet and cancer, cardiovascular disease and diabetes are summarized in Table 2.

3 Jpn J Clin Oncol 2014;44(9) 779 Figure 2. Schedule of the JPHC Study. Figure 3. Number of deaths by cause: SOYS AND ISOFLAVONES Asian populations consume large quantities of soy foods, which contain isoflavones such as genistein and daidzein. Genistein and daidzein exhibit anti-carcinogenic properties and estrogenic or anti-estrogenic activities in vitro, and have demonstrated a protective effect against some cancers in animal studies. They are accordingly recognized as key substances that may decrease the incidence of breast and prostate cancers in Japan. Findings of the dietary record survey indicate that tofu, miso and natto contribute.80% of total isoflavone intake in our population. Our FFQ asked about these three items and an additional four items which together cover 95% of total isoflavone intake. The validity of isoflavone intake from the FFQ (Spearman s correlation coefficient (r) ¼ 0.57 for daidzein and 0.54 for genistein, respectively) against the 4 season 7 (28) day dietary record survey is relatively high, and modest even against serum (r ¼ 0.31 and 0.33) or urine levels (r ¼ 0.29 and 0.20) (1). In the JPHC Study, we found an inverse association between dietary isoflavones and post-menopausal breast cancer (2) and localized prostate cancer (3). We also found that high blood levels of isoflavones were associated with a decreased risk of these cancers in nested case control studies

4 780 JPHC Study: design and some findings Figure 4. Number of registered diseases ( ). Table 2. Typical Japanese diet and cancer: evidence from the JPHC Study Breast Prostate Colon HCC Other cancers CVD Diabetes Soys, isoflavones Fish, n-3 fatty acids esp. post esp. local. Red meat, saturated fat (Saturated fat) Green tea Null esp. adv. :m esp. prox esp. prox. (Red meat) Coffee Null :f esp. inv. Salt/salted foods : f : Lung, never smks null: Stomach : MI, f : Stroke, f esp. infarction :MI :m Null Null : Stomach, f, esp. distal null: Pancreas : Endometrial : Pancreas, m : Bladder, m non smks : Stomach (salted foods) : MI,: stroke (Saturated fat) null: MI : Stroke Null: MI : Stroke : Stroke (salt) :f (overweight) : m (Red meat) HCC, hepatocellular carcinoma; CVD, cardiovascular disease;, risk decreased;, risk increased; esp, especially; post, post-menopausal; local, localized; adv, advanced; prox, proximal; inv, invasive; smks, smokers; f, female; m, male; MI, myocardial infraction. (4,5). In addition, isoflavones were inversely associated with lung cancer among never smokers by dietary intake (6) and among women by plasma level (7); with proximal colon cancer among men (8) and diabetes mellitus among obese women (9); and further with cardiovascular infarction in women (10). No clear association was found for stomach cancer (11). In contrast, isoflavones increased the risk of liver cancer in women (12). FISH/N-3 FATTY ACIDS AND RED MEAT/SATURATED FAT The Japanese population consumes a large amount of fish and seafood, which are rich in n-3 fatty acids, but less meat, which is rich in saturated fat. According to the international FAO database ( food supply quantities (per capita per year) of total fish/seafood and total meat in Japan were estimated to be 69.8 and 23.4 kg in 1975 and 56.6 and 45.9 kg in 2009, respectively. Corresponding figures in the USA were 14.1 and kg in 1975 and 24.1 and kg in 2009, respectively. In general, meat is a typical component of the diet in Western countries and is known to increase the risk of colon cancer and myocardial infarction, while fish intake decreases these diseases. In the JPHC Study, we found an inverse association between fish and n-3 fatty acid and cancers of the proximal colon (13) and liver (14), myocardial infarction (15)andmale

5 Jpn J Clin Oncol 2014;44(9) 781 diabetes (16). No evidence of any harmful health effect of fish and n-3 fatty acids has been obtained to date. We also found that red meat intake was associated with an increased risk of colon cancer (17) and male diabetes (18). Saturated fat intake was associated with an increased risk of prostate cancer (19) and myocardial infarction but a decreased risk of stroke (20). Since the incidence of stroke was much higher than that of myocardial infarction in the JPHC Study (3192 strokes vs. 610 myocardial infarctions), saturated fat intake decreased the risk of cardiovascular diseases in total. 14 g in 1975, according to the National Health and Nutrition survey ( chousa.html). Salt intake is known to increase the risk of hypertension and consequently that of stroke and coronary heart disease (34). Salt and salted food intakes are also known to increase the risk of gastric cancer (35). In the JPHC Study, intake of salted food, such as pickled vegetables and salted fish or fish roe, was associated with an increased risk of stomach cancer, while salt per se was associated with an increased risk of cardiovascular disease (36). GREEN TEA AND COFFEE Green tea is traditionally and widely consumed in Japan. It contains no calories and has a high content of catechins, such as (2)-epigallocatechin-3-gallate and (2)-epicathechin, and may play an important role in cancer prevention through its antioxidant properties, induction of apoptosis, inhibition of cell growth and arrest of cell cycle progression. Coffee is now also widely consumed. Coffee contains large amounts of antioxidants, such as chlorogenic acid, and several animal studies have shown that such coffee compounds have a direct anticarcinogenic effect. Caffeine is another major ingredient of coffee. Several epidemiological studies have shown that coffee consumption is associated with a reduced risk of some cancers and type 2 diabetes via the moderation of insulin resistance. According to National Health and Nutrition survey in 2012 ( html), average consumption among Japanese adults aged 20 years and older was 296 g for teas (mostly green tea) and 151 g for coffee and cocoa (mostly coffee). In the JPHC Study, green tea consumption was associated with a decreased risk of female stomach cancer (21), advanced prostate cancer (22) andstroke(23). In addition, a higher plasma level of (2)-epicatechin-3-gallate (ECG) was associated with a decreased risk of stomach cancer in women in a nested case control study (24). However, no associations have been seen for cancers of the breast (25,26), colon (27), liver (28) and pancreas (29) or for myocardial infarction (23). Coffee consumption has been shown to have a strong protective effect on cancers of the liver (28,30) and endometrium (31), with hazard ratios among daily drinkers of almost half those of non-drinkers. We also found moderate inverse associations with cancers of the female colon (27) and male pancreas (29) and stroke (23) and diabetes (32). However, coffee consumption was associated with an increased risk of male bladder cancer among nonsmokers (33). SALT AND SALTED FOOD The Japanese diet is generally regarded as healthy due to its variety of low calorie and low fat foods. However, a major weakness is its high salt intake from seasonings, such as salt per se; soy sauce and miso; and salted foods, such as pickled vegetables and salted seafood. National average dietary salt intake was estimated to be 10 g per day in 2012, down from FUTURE OF THE JPHC STUDY AND THE JPHC STUDY FOR THE NEXT GENERATION (JPHC-NEXT) The JPHC Study is scheduled to conduct active follow-up for a total of 30 years and plans to publish more evidence, particularly focused on the effects of lifestyle change using repeated questionnaires; factors in longevity and rare events revealed only with longer follow-up; and biomarkers, including multi-omics analysis using stored blood samples. However, lifestyle and living environment have changed dramatically over the last several decades and the number of subjects and biological samples in the JPHC Study allow only limited stratified analysis. A new cohort study is therefore required. We have now launched the JPHC-NEXT, a large-scale cohort study of next-generation subjects by next-generation researchers using next-generation technologies. Following a pilot study in , the main study started in Although most of its concepts and some study areas are similar to those of the JPHC Study, there are new modifications to the questionnaires, biospecimens, informed consent and endpoints. These include tumor tissue collection for cancer cases and inclusion of various diseases as an endpoint using electric medical records. Acknowledgements We are indebted to the Aomori, Iwate, Ibaraki, Niigata, Osaka, Kochi, Nagasaki and Okinawa Cancer Registries for providing their incidence data. Funding This study was supported by National Cancer Center Research and Development Fund (23-A-31[toku] and 26-A-2) (since 2011) and a grant-in-aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan (from 1989 to 2010). Conflict of interest statement None declared.

6 782 JPHC Study: design and some findings References 1. Yamamoto S, Sobue T, Sasaki S, Kobayashi M, Arai Y, Uehara M, et al. Validity and reproducibility of a self-administered food-frequency questionnaire to assess isoflavone intake in a Japanese population in comparison with dietary records and blood and urine isoflavones. JNutr 2001;131: Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S; JPHC Study group. Soy, isoflavones, and breast cancer risk in Japan. J Natl Cancer Inst 2003;95: Kurahashi N, Iwasaki M, Sasazuki S, Otani T, Inoue M, Tsugane S; JPHC Study group. Soy product and isoflavone consumption in relation to prostate cancer in Japanese men. Cancer Epidemiol Biomarkers Prev 2007;16: Iwasaki M, Inoue M, Otani T, Sasazuki S, Kurahashi N, Miura T, et al. Plasma isoflavone level and subsequent risk of breast cancer among Japanese women: a nested case control study from the Japan Public Health Center-based prospective study group. J Clin Oncol 2008;26: Kurahashi N, Iwasaki M, Inoue M, Sasazuki S, Tsugane S. Plasma isoflavones and subsequent risk of prostate cancer in a nested case-control study: the Japan Public Health Center. J Clin Oncol 2008;26: Shimazu T, Inoue M, Sasazuki S, Iwasaki M, Sawada N, Yamaji T, et al. Isoflavone intake and risk of lung cancer: a prospective cohort study in Japan. Am J Clin Nutr 2010;91: Shimazu T, Inoue M, Sasazuki S, Iwasaki M, Sawada N, Yamaji T, et al. Plasma isoflavones and the risk of lung cancer in women: a nested case control study in Japan. Cancer Epidemiol Biomarkers Prev 2011;20: Akhter M, Inoue M, Kurahashi N, Iwasaki M, Sasazuki S, Tsugane S; JPHC Study group. Dietary soy and isoflavone intake and risk of colorectal cancer in the Japan public health center-based prospective study. Cancer Epidemiol Biomarkers Prev 2008;17: Nanri A, Mizoue T, Takahashi Y, Kirii K, Inoue M, Noda M, et al. Soy product and isoflavone intakes are associated with a lower risk of type 2 diabetes in overweight Japanese women. J Nutr 2010;140: Kokubo Y, Iso H, Ishihara J, Okada K, Inoue M, Tsugane S; JPHC Study Group. Association of dietary intake of soy, beans, and isoflavones with risk of cerebral and myocardial infarctions in Japanese populations: the Japan Public Health Center-based (JPHC) study cohort I. Circulation 2007;116: Hara A, Sasazuki S, Inoue M, Iwasaki M, Shimazu T, Sawada N, et al. Isoflavone intake and risk of gastric cancer: a population-based prospective cohort study in Japan. Am J Clin Nutr 2012;95: Kurahashi N, Inoue M, Iwasaki M, Tanaka Y, Mizokami M, Tsugane S; JPHC Study Group. Isoflavone consumption and subsequent risk of hepatocellular carcinoma in a population-based prospective cohort of Japanese men and women. Int J Cancer 2009;124: Sasazuki S, Inoue M, Iwasaki M, Sawada N, Shimazu T, Yamaji T, et al. Intake of n-3 and n-6 polyunsaturated fatty acids and development of colorectal cancer by subsite: Japan Public Health Center-based prospective study. Int J Cancer 2011;129: Sawada N, Inoue M, Iwasaki M, Sasazuki S, Shimazu T, Yamaji T, et al. Consumption of n-3 fatty acids and fish reduces risk of hepatocellular carcinoma. Gastroenterology 2012;142: Iso H, Kobayashi M, Ishihara J, Sasaki S, Okada K, Kita Y, et al. Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based (JPHC) Study Cohort I. Circulation 2006;113: Nanri A, Mizoue T, Noda M, Takahashi Y, Matsushita Y, Poudel-Tandukar K, et al. Fish intake and type 2 diabetes in Japanese men and women: the Japan Public Health Center-based prospective study. Am J Clin Nutr 2011;94: Takachi R, Tsubono Y, Baba K, Inoue M, Sasazuki S, Iwasaki M, et al. Red meat intake may increase the risk of colon cancer in Japanese, a population with relatively low red meat consumption. Asia Pac J Clin Nutr 2011;20: Kurotani K, Nanri A, Goto A, Mizoue T, Noda M, Oba S, et al. Red meat consumption is associated with the risk of type 2 diabetes in men but not in women: a Japan Public Health Center-based Prospective Study. Br J Nutr 2013;110: Kurahashi N, Inoue M, Iwasaki M, Sasazuki S, Tsugane S; Japan Public Health Center-Based Prospective Study Group. Dairy product, saturated fatty acid, and calcium intake and prostate cancer in a prospective cohort of Japanese men. Cancer Epidemiol Biomarkers Prev 2008;17: Yamagishi K, Iso H, Kokubo Y, Saito I, Yatsuya H, Ishihara J, et al. Dietary intake of saturated fatty acids and incident stroke and coronary heart disease in Japanese communities: the JPHC Study. Eur Heart J 2013;34: Sasazuki S, Inoue M, Hanaoka T, Yamamoto S, Sobue T, Tsugane S. Green tea consumption and subsequent risk of gastric cancer by subsite: the JPHC Study. Cancer Causes Control 2004;15: Kurahashi N, Sasazuki S, Iwasaki M, Inoue M, Tsugane S; JPHC Study Group. Green tea consumption and prostate cancer risk in Japanese men: a prospective study. Am J Epidemiol 2008;167: Kokubo Y, Iso H, Saito I, Yamagishi K, Yatsuya H, Ishihara J, et al. The impact of green tea and coffee consumption on the reduced risk of stroke incidence in Japanese population: the Japan public health center-based study cohort. Stroke 2013;44: Sasazuki S, Inoue M, Miura T, Iwasaki M, Tsugane S; Japan Public Health Center-based Prospective Study Group. Plasma tea polyphenols and gastric cancer risk: a case control study nested in a large population-based prospective study in Japan. Cancer Epidemiol Biomarkers Prev 2008;17: Iwasaki M, Inoue M, Sasazuki S, Sawada N, Yamaji T, Shimazu T, et al. Green tea drinking and subsequent risk of breast cancer in a population-based cohort of Japanese women. Breast Cancer Res 2010;12:R Iwasaki M, Inoue M, Sasazuki S, Miura T, Sawada N, Yamaji T, et al. Plasma tea polyphenol levels and subsequent risk of breast cancer among Japanese women: a nested case control study. Breast Cancer Res Treat 2010;124: Lee KJ, Inoue M, Otani T, Iwasaki M, Sasazuki S, Tsugane S; JPHC Study Group. Coffee consumption and risk of colorectal cancer in a population-based prospective cohort of Japanese men and women. Int J Cancer 2007;121: Inoue M, Kurahashi N, Iwasaki M, Shimazu T, Tanaka Y, Mizokami M, et al. Effect of coffee and green tea consumption on the risk of liver cancer: cohort analysis by hepatitis virus infection status. Cancer Epidemiol Biomarkers Prev 2009;18: Luo J, Inoue M, Iwasaki M, Sasazuki S, Otani T, Ye W, Tsugane S; JPHC Study Group. Green tea and coffee intake and risk of pancreatic cancer in a large-scale, population-based cohort study in Japan (JPHC study). Eur J Cancer Prev 2007;16: Inoue M, Yoshimi I, Sobue T, Tsugane S; JPHC Study Group. Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: a prospective study in Japan. J Natl Cancer Inst 2005;97: Shimazu T, Inoue M, Sasazuki S, Iwasaki M, Kurahashi N, Yamaji T, et al. Coffee consumption and risk of endometrial cancer: a prospective study in Japan. Int J Cancer 2008;123: Kato M, Noda M, Inoue M, Kadowaki T, Tsugane S; JPHC Study Group. Psychological factors, coffee and risk of diabetes mellitus among middle-aged Japanese: a population-based prospective study in the JPHC study cohort. Endocr J 2009;56: Kurahashi N, Inoue M, Iwasaki M, Sasazuki S, Tsugane S; Japan Public Health Center (JPHC) Study Group. Coffee, green tea, and caffeine consumption and subsequent risk of bladder cancerin relation to smoking status: a prospective study in Japan. Cancer Sci 2009;100: Aburto NJ, Ziolkovska A, Hooper L, Elliott P, Cappuccio FP, Meerpohl JJ. Effect of lower sodium intake on health: systematic review and meta-analyses. BMJ 2013;346:f Tsugane S. Salt, salted food intake, and risk of gastric cancer: epidemiologic evidence. Cancer Sci 2005;96: Takachi R, Inoue M, Shimazu T, Sasazuki S, Ishihara J, Sawada N, et al. Consumption of sodium and salted foods in relation to cancer and cardiovascular disease: the Japan Public Health Center-based Prospective Study. Am J Clin Nutr 2010;91: