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Journal of Epidemiology logoLink to Journal of Epidemiology
. 2017 Jan 5;27(4):193–199. doi: 10.1016/j.je.2016.05.003

Rationale, design, and profile of the Three-Prefecture Cohort in Japan: A 15-year follow-up

Junya Sado a, Tetsuhisa Kitamura a, Yuri Kitamura a,, Ling Zha a, Rong Liu a, Tomotaka Sobue a, Yoshikazu Nishino b, Hideo Tanaka c, Tomio Nakayama d, Ichiro Tsuji e, Hidemi Ito c, Takaichiro Suzuki d, Kota Katanoda f, Suketami Tominaga c; for the Three-Prefecture Cohort Study Group
PMCID: PMC5376309  PMID: 28142030

Abstract

Background

We reutilized the existing Three-Prefecture Cohort to evaluate the relationship between lifestyle factors and the incidence or mortality from non-communicable diseases.

Methods

This study was a prospective population-based observation conducted from the 1980s to 2000 in three prefectures (Miyagi, Aichi, and Osaka) in Japan. The study subjects were residents aged ≥40 years who received a questionnaire. The follow-up period was 15 years from the baseline survey in each study area. A self-administered questionnaire, which included items on participants' demographic factors and lifestyle characteristics, was administered. Vital status and date of death were collected from residence certificates by the local government, and cause of death was identified using vital statistics. Cancer incidence and the date of diagnosis were collected from local cancer registry data.

Results

A total of 46,421 men and 54,189 women were eligible for our analysis. The person-years of follow-up for cancer incidence were 464,664 and 567,271 for men and women, respectively, and those for death were 527,940 and 648,601 for men and women, respectively. There were 8479 cancer incidences (5106 men and 3373 women) and 20,240 total deaths (11,156 men and 9084 women). The stomach was the most common cancer incidence site for both men (25.6%) and women (18.6%). The leading cause of death was cancer among men (35.0%) and cardiovascular disease among women (41.0%).

Conclusions

The Three-Prefecture Cohort Study enabled us to reveal the association of multiphasic lifestyle factors with cancer incidence and mortality. The study will also allow us to conduct a pooled analysis in combination with other large-scale cohorts.

Keywords: Cohort, Cancer, Incidence, Mortality, The Three-Prefecture Cohort

Highlights

  • The Three-Prefecture Cohort had about 100,000 participants in urban and rural areas.

  • This cohort collected detailed information on participants' lifestyles.

  • This cohort had data on participants' cancer incidence and mortality.

Introduction

A cohort study is one of the ways to evaluate the relationship between lifestyle factors and the incidence or mortality from non-communicable diseases. Although huge amounts of money and long-term observation are needed to conduct a cohort study, such a design could minimize selection bias and maximized external validity. Large-scale prospective cohorts focused on healthy populations (e.g., the Japan Collaborative Cohort [JACC] Study1 or the Japan Public Health-Based Prospective Cohort [JPHC] Study2) have been conducted since 1980s in Japan. There have also been large cohort studies worldwide, such as the National Institutes of Health–American Association of Retired Persons Diet and Health Study in the United States,3 the European Prospective Investigation into Cancer and Nutrition in Europe,4 and the Korean Multi-center Cancer Cohort Study in Korea.5 Indeed, many findings have been obtained from these studies.

The Three-Prefecture Cohort Study was a prospective population-based observational study launched in 1983, which targeted approximately 100,000 inhabitants in Miyagi Prefecture, Aichi Prefecture, and Osaka Prefecture in Japan and conducted a questionnaire survey to reveal the association of multiphasic lifestyle factors with cancer incidence or mortality. Here, we briefly described the study concept and the cohort population's profile.

Materials and methods

Study design and settings

This cohort, which has been under prospective observation since 1983, was studied to assess the long-term effects of air pollution on mortality from lung cancer and respiratory diseases.6, 7 The study areas were chosen because they contained a national air monitoring station and had well-managed cancer surveillance systems in 1983, including eight selected urban/rural areas in Miyagi Prefecture (Sendai City and Wakuya/Tajiri Town), Aichi Prefecture (Nagoya City and Inuyama City), and Osaka Prefecture (Osaka City and Nose/Kanan/Kumatori Town). Since the 1970s, there has been a network of ambient air monitoring stations in Japan operated by the Ministry of Environment (formerly the National Environment Agency) and local governments. In this study, we defined rural areas as cities/towns with general air pollution monitoring stations (control area) and urban areas as cities/towns with automobile exhaust gas measurement stations (pollution area).6 Self-administered questionnaires in sealed envelopes were distributed by hand to targeted individuals in cooperation with the municipal government in each area and were collected after a set period of time. The study committee, consisting of health center directors, local officials, and residents' association representatives, was established to protect personal information of the participants and ensure the accuracy of the study. In this study, we merged individuals' data with their cancer incidence information based on personal name, gender, and date of birth. The proportion of death certificate only (DCO) deaths in each area was 9.1%–17.8% in Miyagi Prefecture,8 28.1%–32.6% in Aichi Prefecture,9 and 20.7%–23.4% in Osaka Prefecture.10

The study subjects were residents aged ≥40 years who received a questionnaire, and they were enrolled between 1983 and 1985. The investigation was begun in Osaka Prefecture in 1983, in Miyagi Prefecture in 1984, and in Aichi Prefecture in 1985. The number of questionnaire responders was 17,195/17,805 (96.6%) in Sendai City, 14,574/14,926 (97.6%) in Wakuya/Tajiri Town, 21,535/23,331 (92.3%) in Nagoya City, 12,003/12,815 (93.7%) in Inuyama City, 20,665/27,051 (76.4%) in Osaka City, and 18565/21,101 (88.0%) in Nose/Kanan/Kumatori Town (Table 1). Of 104,537 responders, a total of 100,629 were included as subjects, after excluding those who answered a questionnaire in duplicate or did not provide their name/gender/date of birth because investigators could not follow up the outcome data in the Three-Prefecture Cohort study.

Table 1.

Participants of the Three-Prefecture Cohort study.

Miyagi Prefecture
Aichi Prefecture
Osaka Prefecture
Total
Sendai-City (6 areas in Aoba and Miyagino wards) Wakuya/Tajiri-Towns (Entire towns) Nagoya-City (5 areas in Chigusa ward) Inuyama-City (2 areas in the city) Osaka-City (Higashinari ward) Nose/Kanan/Kumatori-Town (Entire towns)
All residents aged ≥40 years old 25,237 15,891 24,489 12,854 39,307 21,230 139,008
Delivered questionnaires 17,805 14,926 23,331 12,815 27,051 21,101 117,029
Responded questionnaires 17,195 14,574 21,535 12,003 20,665 18,565 104,537
Response rate (%)a (68.1) (91.7) (87.9) (93.4) (52.6) (87.4) (75.2)
Response rate (%)b (96.6) (97.6) (92.3) (93.7) (76.4) (88.0) (89.3)
a

Denominator was subjects who were all residents aged ≥40 years old.

b

Denominator was subjects who were delivered the self-administrated questionnaire.

Questionnaire

Baseline questionnaire items included the following: area of residence, gender, height, weight, health condition at that time, past medical history, type of insurance, health check-up/cancer screening history, frequency of food intake, smoking, alcohol drinking status, parent's medical history, smoking status of cohabitants, house environment, occupation (such as the longest period of employment), and reproductive history (only for women). Medical history included: past history of diabetes mellitus, hypertension, stroke, and emphysema; and stomach cancer screening by x-ray examination, blood pressure measurement, and uterus cancer screening (only for women). Food intake frequency of items, such as rice, bread, meat, fish, eggs, milk, green/yellow vegetables, non-green/yellow vegetables, fruit, miso soup, and pickled vegetables, as well as drinking beverages, such as green tea, black tea, and coffee, was assessed categorically.

Follow-up

The follow-up period was defined as 15 years from the baseline survey in each study area, except for cancer incidence data in Miyagi Prefecture, for which follow-up was 9 years. The cohorts were followed from 1984 to 1999 in Miyagi Prefecture, from 1985 to 2000 in Aichi Prefecture, and from 1983 to 2000 in Osaka Prefecture. Vital status, date of death, and date of move-out from the study area were confirmed by the local government using residence certificates. Cause of death was identified using death certificate. Cancer incidence and the date of diagnosis were collected from local cancer registry data.

Statistical analysis

The definition of disease was determined based on the International Classification of Diseases 9th version (ICD-9) for data collected from 1983 to 1994 and or the 10th version (ICD-10) for data collected from 1995 to 2000 in this study. We counted the number of incident cancers and deaths of all cancer and cancer of individual sites, and also the number of deaths according to cause of death. When mortality rates were calculated, person-years of follow-up for mortality were counted from the date of the baseline survey to the date of death, date of move-out from the study area, or the end of 15-year follow-up (whichever occurred first). For cancer incidence rates, date of diagnosis of first primary cancer was added to the above list. In addition, standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) of all-cause and all cancer were calculated using age-adjusted mortality/incidence rate, which was calculated using 5-year age-specific rates in each year according to the cancer registry and vital statistics in Japan.11, 12 Statistical analyses were implemented using STATA version 13 MP (Stata Corp., College Station, TX, USA).

Ethics

The study was approved by the institutional review board of the National Cancer Center and the Ethics Committee of Osaka University School of Medicine. We received permission from the municipal governments to survey residents. The response to the questionnaire by participant was considered consent to participate in the survey. Tohoku University, Aichi Cancer Center, and Osaka Medical Center for Cancer and Cardiovascular Diseases were primarily responsible for analyzing information on baseline surveys, linking with cancer incidence and cause of death data, and altering the data set to unlinkable anonymized data. Although the National Cancer Center had originally managed the integrated datasets, Osaka University manages them at present. In the Three-Prefecture Cohort study, researchers only analyzed unlinkable anonymous data.

Results

Of 100,629 participants aged 40–99 years old at baseline, 19 (0.02%) were excluded because their responses preceded the date of beginning of follow-up, which was unified in each area after various dates of individual response to the questionnaire. As a result, 46,421 men and 54,189 women were eligible for this study. Details of the distribution of cohort participants at baseline by sex, age, and region are noted in Table 2. The person-years of follow-up for cancer incidence were 464,664 and 567,271 for men and women, respectively, and the person-years for death were 527,940 and 648,601 for men and women, respectively.

Table 2.

Distribution of cohort participants at baseline by gender, age, and region.

Age at baseline, years
Total %
40–44 45–49 50–54 55–59 60–64 65–69 70–74 75–79 80–84 ≥85
Men
 Japan census population 1985 (x1,000) 4494 4053 3898 3391 2349 1771 1486 997 546 247 23,232
 % 19.3 17.4 16.8 14.6 10.1 7.6 6.4 4.3 2.4 1.1 100.0
 Three-prefecture cohort participants 8082 7735 7795 6804 5018 4067 3410 2153 973 384 46,421
 % 17.4 16.7 16.8 14.7 10.8 8.8 7.3 4.6 2.1 0.8 100.0
 Miyagi Prefecture (urban) 1137 1161 1194 1057 859 765 586 371 189 72 7391 15.9
 Miyagi Prefecture (rural) 903 1020 1213 1082 784 607 490 333 116 53 6601 14.2
 Aichi Prefecture (urban) 1841 1821 1760 1358 1035 818 675 442 220 74 10,044 21.6
 Aichi Prefecture (rural) 1095 989 963 823 561 476 377 250 109 49 5692 12.3
 Osaka Prefecture (urban) 990 1161 1265 1183 927 764 718 440 193 67 7708 16.6
 Osaka Prefecture (rural) 2116 1583 1400 1301 852 637 564 317 146 69 8985 19.4
Women
 Japan census population 1985 (x1,000) 4554 4140 3971 3574 3011 2394 2046 1438 906 525 26,559
 % 17.1 15.6 15.0 13.5 11.3 9.0 7.7 5.4 3.4 2.0 100.0
 Three-prefecture cohort participants 8522 8522 8337 7814 6604 5196 4261 2722 1471 740 54,189
 % 15.7 15.7 15.4 14.4 12.2 9.6 7.9 5.0 2.7 1.4 100.0
 Miyagi Prefecture (urban) 1318 1447 1508 1379 1234 937 740 453 257 110 9383 17.3
 Miyagi Prefecture (rural) 938 1161 1354 1268 1009 758 717 391 220 154 7970 14.7
 Aichi Prefecture (urban) 1911 1944 1785 1621 1361 1020 843 578 264 141 11,468 21.2
 Aichi Prefecture (rural) 1071 1050 897 869 711 638 459 346 171 94 6306 11.6
 Osaka Prefecture (urban) 1264 1380 1404 1377 1246 1031 820 501 291 125 9439 17.4
 Osaka Prefecture (rural) 2020 1540 1389 1300 1043 812 682 453 268 116 9623 17.8

Table 3 shows selected baseline characteristics of participants by sex. Mean age among men and women was 56.1 and 57.1 years, respectively, and the proportion of participants with a body mass index of 22.0–24.9 kg/m2 was 37.0% among men and 31.9% among women. The proportion of current drinkers of alcoholic beverages was 46.9% for men and 5.4% for women, and the proportion of current smokers was 51.6% for men and 9.6% for women. Regarding the longest period occupational classification, the proportion of participants engaged in clerical work was 11.7% among men and 9.6% among women, and the proportion of those unemployed was 2.8% among men and 19.7% among women.

Table 3.

Selected baseline demographic and lifestyle characteristics of participants by gender.

Men
Women
(n = 46,421) (n = 54,189)
Mean age, years (standard deviation) 56.1 (11.2) 57.1 (11.6)
Regions, n (%)
 Miyagi, urban 7391 (15.9) 9383 (17.3)
 Miyagi, rural 6601 (14.2) 7970 (14.7)
 Aichi, urban 10,044 (21.6) 11,468 (21.2)
 Aichi, rural 5692 (12.3) 6306 (11.6)
 Osaka, urban 7708 (16.6) 9439 (17.4)
 Osaka, rural 8985 (19.4) 9623 (17.8)
Health insurance type, n (%)
 National health insurance 20,877 (45.0) 25,263 (46.6)
 Government/union-managed health insurance 19,267 (41.5) 20,864 (38.5)
 Mutual aid associations health insurance 3897 (8.4) 4250 (7.8)
 Others 577 (1.2) 891 (1.6)
 Missing 1803 (3.9) 2921 (5.4)
History of hypertension, n (%)
 Current 8289 (17.9) 10,138 (18.7)
 Past 1709 (3.7) 2189 (4.0)
 Never 19,820 (42.7) 23,811 (43.9)
 Missing 16,603 (35.8) 18,051 (33.3)
History of diabetes, n (%)
 Current 2725 (5.9) 1803 (3.3)
 Past 738 (1.6) 275 (0.5)
 Never 20,895 (45.0) 25,586 (47.2)
 Missing 22,063 (47.5) 26,525 (48.9)
Body mass index, n (%)
 ≤19.0 kg/m2 4310 (9.3) 6255 (11.5)
 19.0–21.9 kg/m2 14,995 (32.3) 17,153 (31.7)
 22.0–24.9 kg/m2 17,155 (37.0) 17,294 (31.9)
 25.0–29.9 kg/m2 7528 (16.2) 9378 (17.3)
 ≥30.0 kg/m2 515 (1.1) 1130 (2.1)
 Missing 1918 (4.1) 2979 (5.5)
Alcohol drinking, n (%)
 Never 7122 (15.3) 26,119 (48.2)
 Former 2787 (6.0) 1094 (2.0)
 Current occasional 11,884 (25.6) 13,497 (24.9)
 Current almost daily 21,776 (46.9) 2942 (5.4)
 Missing 2852 (6.1) 10,537 (19.4)
Smoking status, n (%)
 Never 7411 (16.0) 37,281 (68.8)
 Former 10,805 (23.3) 1746 (3.2)
 Current 23,969 (51.6) 5199 (9.6)
 Missing 4236 (9.1) 9963 (18.4)
Green and yellow vegetable consumption, n (%)
 ≤1–2 times/month 3311 (7.1) 2183 (4.0)
 1–2 times/week 10,320 (22.2) 8563 (15.8)
 3–4 times/week 12,623 (27.2) 14,918 (27.5)
 Almost daily 17,509 (37.7) 24,445 (45.1)
 Missing 2658 (5.7) 4080 (7.5)
Non-green and non-yellow vegetable consumption, n (%)
 ≤1–2 times/month 1491 (3.2) 1111 (2.1)
 1–2 times/week 6634 (14.3) 5229 (9.6)
 3–4 times/week 12,267 (26.4) 12,816 (23.7)
 Almost daily 23,782 (51.2) 31,276 (57.7)
 Missing 2247 (4.8) 3757 (6.9)
Fruit consumption, n (%)
 ≤1–2 times/month 5040 (10.9) 2452 (4.5)
 1–2 times/week 9631 (20.7) 6291 (11.6)
 3–4 times/week 10,303 (22.2) 10,649 (19.7)
 Almost daily 18,308 (39.4) 30,535 (56.3)
 Missing 3139 (6.8) 4262 (7.9)
Miso soup consumption, n (%)
 ≤1–2 times/month 3141 (6.8) 3823 (7.1)
 1–2 times/week 7127 (15.4) 8473 (15.6)
 3–4 times/week 8035 (17.3) 9746 (18.0)
 Almost daily 25,913 (55.8) 28,213 (52.1)
 Missing 2205 (4.8) 3934 (7.3)
Pickled vegetable consumption, n (%)
 Scarcely any 2296 (4.9) 2095 (3.9)
 1–2 times/month 2311 (5.0) 2380 (4.4)
 1–2 times/week 5114 (11.0) 5340 (9.9)
 3–4 times/week 6508 (14.0) 6753 (12.5)
 Almost daily 27,016 (58.2) 32,802 (60.5)
 Missing 3176 (6.8) 4819 (8.9)
Type of job, n (%)
 Professional technical and civil workers 3835 (8.3) 2805 (5.2)
 Managerial workers 959 (2.1) 98 (0.2)
 Clerical workers 5415 (11.7) 5197 (9.6)
 Sales workers 5495 (11.8) 3663 (6.8)
 Agricultural, forestry and fisheries workers 2844 (6.1) 3127 (5.8)
 Construction workers 92 (0.2) 9 (0.0)
 Workers in transport and communications 1814 (3.9) 309 (0.6)
 Craftsman, production process worker, and laborers 9537 (20.5) 4740 (8.7)
 Workers in security 567 (1.2) 18 (0.0)
 Service workers 1069 (2.3) 2750 (5.1)
 Unemployed 1284 (2.8) 10,666 (19.7)
 Missing 13,510 (29.1) 20,807 (38.4)

Table 4 shows the follow-up results, Table 5 lists major types of incident cancers, and Table 6 lists major causes of death by gender. There were 20,240 total deaths (20.1%; 11,156 men and 9084 women), and 20,281 move-outs (20.2%; 9145 men and 11,136 women) (Table 4). The SIR of all cancers was 0.96 among men and 1.22 among women. The SMR of all causes was 0.91 among men and women, and the SMR of all cancers was 1.02 among men and 0.97 among women. Stomach cancer was the most frequent cancer among men (25.5%) and women (18.7%), followed by lung cancer among men (17.1%) and breast cancer among women (13.0%) (Table 5). The leading cause of death was cancer among men (35.0%) and cardiovascular disease among women (41.0%), and the second-leading cause of death was cardiovascular disease among men (33.0%) and cancer among women (25.7%) (Table 6). Among those who died of cancer, the first-, second-, and third-leading causes of death were cancer of the lung (21.9%), stomach (21.2%), and liver (14.4%) among men, and cancer of the stomach (18.7%), colon/rectum (13.2%), and lung (11.8%) among women.

Table 4.

15-year follow-up status until 2000 by gender and age.

Age at baseline, years
Total
40–44 45–49 50–54 55–59 60–64 65–69 70–74 75–79 80–84 ≥85
Men
 Number at baseline 8082 7735 7795 6804 5018 4067 3410 2153 973 384 46,421
 Number of all cancer incidences 215 371 665 891 841 802 712 414 159 36 5106
 % (Number of all cancer incidences/Number at baseline) 2.7 4.8 8.5 13.1 16.8 19.7 20.9 19.2 16.3 9.4 11.0
 Number of deaths 320 506 960 1268 1407 1790 2054 1642 850 359 11,156
 % (Number of all cause deaths/Number at baseline) 4.0 6.5 12.3 18.6 28.0 44.0 60.2 76.3 87.4 93.5 24.0
 Number of all cancer deaths 135 230 463 642 615 641 626 375 140 35 3902
 % (Number of all cancer deaths/Number at baseline) 1.7 3.0 5.9 9.4 12.3 15.8 18.4 17.4 14.4 9.1 8.4
 Number who left study area 2359 1991 1608 1151 735 558 421 226 80 16 9145
 % (Number who left study area/Number at baseline) 29.2 25.7 20.6 16.9 14.6 13.7 12.3 10.5 8.2 4.2 19.7
 Person-years (incidence) 87,758 83,560 83,345 71,783 50,831 37,773 28,223 14,550 5175 1666 464,664
 Incidence rate (all cancer per 1000 person-years) 2.4 4.4 8.0 12.4 16.5 21.2 25.2 28.5 30.7 21.6 11.0
 Person-years (mortality) 96,389 93,649 95,428 83,102 59,579 44,107 32,193 16,278 5500 1714 527,940
 Mortality rate (all cause per 1000 person-years) 3.3 5.4 10.1 15.3 23.6 40.6 63.8 100.9 154.5 209.4 21.1
 Mortality rate (all cancer per 1000 person-years) 1.4 2.5 4.9 7.7 10.3 14.5 19.4 23.0 25.5 20.4 7.4
Women
 Number at baseline 8522 8522 8337 7814 6604 5196 4261 2722 1471 740 54,189
 Number of cancer incidences 229 291 386 483 513 539 478 296 121 37 3373
 % (Number of all cancer incidences/Number at baseline) 2.7 3.4 4.6 6.2 7.8 10.4 11.2 10.9 8.2 5.0 6.2
 Number of deaths 181 301 446 662 946 1365 1712 1648 1157 666 9084
 % (Number of all cause deaths/Number at baseline) 2.1 3.5 5.3 8.5 14.3 26.3 40.2 60.5 78.7 90.0 16.8
 Number of all cancer deaths 98 170 211 286 325 410 404 278 115 34 2331
 % (Number of all cancer deaths/Number at baseline) 1.1 2.0 2.5 3.7 4.9 7.9 9.5 10.2 7.8 4.6 4.3
 Number who left study area 2242 2051 1693 1483 1233 1012 758 440 166 58 11,136
 % (Number who left study area/Number at baseline) 26.3 24.1 20.3 19.0 18.7 19.5 17.8 16.2 11.3 7.8 20.6
 Person-years (incidence) 94,984 94,636 92,190 85,763 71,427 53,084 40,224 22,468 9322 3172 567,271
 Incidence rate (all cancer per 1000 person-years) 2.4 3.1 4.2 5.6 7.2 10.2 11.9 13.2 13.0 11.7 5.9
 Person-years (mortality) 105,776 107,461 107,287 100,096 83,052 60,982 46,008 24,740 9927 3272 648,601
 Mortality rate (all cause per 1000 person-years) 1.7 2.8 4.2 6.6 11.4 22.4 37.2 66.6 116.6 203.5 14.0
 Mortality rate (all cancer per 1000 person-years) 0.9 1.6 2.0 2.9 3.9 6.7 8.8 11.2 11.6 10.4 3.6

Table 5.

Distribution of number of cancer incidence by site, gender, and age at baseline during 15-year follow-up.

ICD10 ICD9 Age at baseline, years
Total %
40–44 45–49 50–54 55–59 60–64 65–69 70–74 75–79 80–84 ≥85
Men
 C00-C97 140–208.9 all cancer 215 371 665 891 841 802 712 414 159 36 5106 100.0
 C15 150–150.9 Esophagus 14 20 25 43 35 29 29 8 4 0 207 4.1
 C16 151–151.9 Stomach 52 94 180 235 224 191 187 95 34 10 1302 25.5
 C18 153–153.9 Colon 26 40 78 74 75 75 52 37 19 1 477 9.3
 C19-20 154–154.9 Rectum 18 28 29 44 46 33 23 21 3 1 246 4.8
 C22 155–155.9 Liver and intrahepatic bile ducts 24 58 117 137 82 83 57 33 15 2 608 11.9
 C23 156 Gall bladder 0 2 3 3 2 3 4 2 0 0 19 0.4
 C24 156.1–156.9 Other and unspecified parts of biliary tract 4 4 11 9 11 20 15 8 4 2 88 1.7
 C25 157–157.9 Pancreas 10 10 19 34 37 33 29 21 8 2 203 4.0
 C33-34 162–162.9 Lung 24 38 79 120 160 174 160 85 25 8 873 17.1
 C61 185–185.9 Prostate 1 7 10 39 31 41 35 25 15 2 206 4.0
 C64 189–189.1 Kidney 3 10 8 21 14 11 8 7 0 0 82 1.6
 C65-67 189.2–189.4 Urothelial tract 2 9 4 11 9 13 11 3 2 0 64 1.3
 C82-85 202–202.9 Non-Hodgkin's 3 5 10 10 12 7 8 5 2 3 65 1.3
200–200.9
 C90 203–203.8 Multiple myeloma 1 0 5 3 8 3 0 3 1 0 24 0.5
 C92 205–205.9 Myeloid leukemia 4 3 7 6 5 7 3 3 1 2 41 0.8
Women
 C00-C97 140–208.9 all cancer 229 291 386 483 513 539 478 296 121 37 3373 100.0
 C15 150–150.9 Esophagus 0 1 1 4 4 5 5 5 0 0 25 0.7
 C16 151–151.9 Stomach 32 49 59 83 104 103 96 63 35 6 630 18.7
 C18 153–153.9 Colon 10 35 44 54 53 67 59 41 12 6 381 11.3
 C19-20 154–154.9 Rectum 15 15 24 25 29 28 27 11 10 2 186 5.5
 C22 155–155.9 Liver and intrahepatic bile ducts 5 14 22 31 38 43 29 11 8 2 203 6.0
 C23 156 Gall bladder 0 3 3 3 5 5 4 6 0 0 29 0.9
 C24 156.1–156.9 Other and unspecified parts of biliary tract 2 3 5 8 12 21 16 13 5 2 87 2.6
 C25 157–157.9 Pancreas 3 6 9 26 25 35 28 19 5 1 157 4.7
 C33-34 162–162.9 Lung 16 8 26 42 52 56 60 34 10 5 309 9.2
 C50 174–175.9 Breast 72 74 71 73 58 42 30 13 6 0 439 13.0
 C53 180–180.9 Cervi uteri 16 17 8 22 15 14 17 8 1 0 118 3.5
 C54 182–182.9 Corpus uteri 9 13 22 15 7 8 4 0 0 0 78 2.3
 C55 184–184.9 Uterus, part unspecified 0 0 1 1 2 3 1 1 2 0 11 0.3
 C56 183–183.9 Ovary 15 13 18 12 8 10 12 7 4 0 99 2.9
 C64 189–189.1 Kidney 2 1 4 3 2 2 5 1 3 0 23 0.7
 C65-67 189.2–189.4 Urothelial tract 0 0 4 3 5 7 3 3 0 1 26 0.8
 C82-85 200–200.9 Non-Hodgkin's 2 3 4 10 7 6 6 5 4 1 48 1.4
202–202.9
 C90 203–203.8 Multiple myeloma 0 0 3 4 4 4 6 3 1 1 26 0.8
 C92 205–205.9 Myeloid leukemia 4 5 3 4 3 6 1 2 0 0 28 0.8

Table 6.

Distribution of number of deaths by cause, gender, and age at baseline during 15-year follow-up.

ICD10 ICD9 Age at baseline, years
Total % %
40–44 45–49 50–54 55–59 60–64 65–69 70–74 75–79 80–84 ≥85
Men
 All causes 320 506 960 1268 1407 1790 2054 1642 850 359 11,156 100.0
 A00-B99 1–139.8 Certain infectious and parasitic diseases 22 11 38 40 31 46 35 28 10 6 267 2.4
 C00-C97 140–208.9 all cancer 135 230 463 642 615 641 626 375 140 35 3902 35.0 100.0
 C15 150–150.9 Esophagus 15 13 22 41 32 27 26 9 7 0 192 4.9
 C16 151–151.9 Stomach 28 39 104 126 120 137 151 84 29 11 829 21.2
 C18 153–153.9 Colon 10 17 38 40 41 47 33 30 13 1 270 6.9
 C19-20 154–154.9 Rectum 10 10 20 25 27 19 19 19 4 1 154 3.9
 C22 155–155.9 Liver and intrahepatic bile ducts 16 52 107 127 80 76 60 29 14 2 563 14.4
 C23 156 Gall bladder 0 4 4 4 10 9 6 4 0 1 42 1.1
 C24 156.1–156.9 Other and unspecified parts of biliary tract 3 6 11 8 13 21 14 12 5 2 95 2.4
 C25 157–157.9 Pancreas 9 14 21 39 41 36 33 23 6 2 224 5.7
 C33-34 162–162.9 Lung 22 36 66 123 152 165 171 89 24 8 856 21.9
 C61 185–185.9 Prostate 0 4 7 11 20 27 24 16 13 1 123 3.2
 C64 189–189.1 Kidney 0 3 3 6 8 8 6 3 0 0 37 0.9
 C65-67 189.2–189.4 Urothelial tract 0 0 1 4 2 3 3 1 0 0 14 0.4
 C82-85 200–200.9 Non-Hodgkin's 3 2 9 12 11 10 13 8 2 2 72 1.8
202–202.9
 C90 203–203.8 Multiple myeloma 1 1 3 2 5 3 2 3 0 0 21 0.5
 C92 205–205.9 Myeloid leukemia 3 3 6 5 8 6 4 2 1 2 40 1.0
 E00-E89 240–279.9 Endocrine, nutritional and metabolic diseases 0 6 9 14 20 29 19 26 17 3 143 1.3
 G00-G99 330–359.9 Diseases of the nervous system 1 5 6 9 12 18 10 8 3 0 72 0.6
 I00-I99 390–459.9 Diseases of the circulatory system 76 121 242 304 407 578 772 644 364 173 3681 33.0
 I20-I25 410–414.9 Ischemic heart disease 16 33 62 74 116 142 176 115 60 16 810
 I48 427.3 Atrial fibrillation and flutter 0 0 3 2 1 6 7 6 4 2 31
 I50 428–428.9 Heart failure 23 32 48 53 74 107 182 181 94 50 844
 I60-69 430–438.9 Cerebrovascular disease 26 42 87 130 143 216 308 270 166 88 1476
 I71 441–441.9 Aortic aneurysm and dissection 2 2 5 8 15 21 13 8 5 2 81
 J00-J99 460–519.9 Diseases of the respiratory system 4 14 41 76 134 255 351 299 161 59 1394 12.5
 J10-J18 480–487.9 Influenza 1 8 15 46 68 139 228 198 113 40 856
 J43 492 Emphysema 0 0 5 5 5 22 19 14 4 5 79
 K00-K93 520–579.9 Diseases of the digestive system 21 39 63 61 59 69 62 59 27 6 466 4.2
 K74 571.5–571.6 Fibrosis and cirrhosis of liver 7 14 38 26 22 17 12 10 6 0 152
 N00-N99 580–629.9 Diseases of the genitourinary system 4 7 12 29 36 37 57 53 25 8 268 2.4
 N17-N19 584–586 Acute kidney failure and chronic kidney disease 3 7 11 21 32 28 48 43 17 2 212
 R00-R99 780–799.9 Symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified 7 3 5 15 17 33 51 80 67 56 334 3.0
 R54 797 Age-related physical debility 1 0 0 1 1 11 15 57 52 55 193
 S00-T88 800–999.9 External causes 42 56 60 57 53 43 41 35 21 5 413 3.7
Others 8 14 21 21 23 41 30 35 15 8 216 1.9
Women
 All causes 181 301 446 662 946 1365 1712 1648 1157 666 9084 100.0
 A00-B99 1–139.8 Certain infectious and parasitic diseases 6 7 21 24 36 31 38 33 21 4 221 2.4
 C00-C97 140–208.9 all cancer 98 170 211 286 325 410 404 278 115 34 2331 25.7 100.0
 C15 150–150.9 Esophagus 0 0 2 6 2 4 8 5 3 0 30 1.3
 C16 151–151.9 Stomach 15 29 35 49 51 74 80 65 31 7 436 18.7
 C18 153–153.9 Colon 5 16 22 27 25 30 46 33 10 5 219 9.4
 C19-20 154–154.9 Rectum 3 10 13 16 13 19 16 10 9 2 111 4.8
 C22 155–155.9 Liver and intrahepatic bile ducts 4 14 14 26 40 38 30 11 8 2 187 8.0
 C23 156 Gall bladder 1 2 7 9 8 19 15 9 1 0 71 3.0
 C24 156.1–156.9 Other and unspecified parts of biliary tract 3 6 8 7 13 21 14 16 7 2 97 4.2
 C25 157–157.9 Pancreas 5 6 12 32 25 40 30 18 6 2 176 7.6
 C33-34 162–162.9 Lung 11 12 17 36 38 55 57 33 11 5 275 11.8
 C50 174–175.9 Breast 23 29 22 16 22 16 11 8 3 0 150 6.4
 C53 180–180.9 Cervi uteri 5 4 1 4 7 8 5 4 0 0 38 1.6
 C54 182–182.9 Corpus uteri 1 4 4 3 0 3 7 0 0 0 22 0.9
 C55 184–184.9 Uterus, part unspecified 0 0 0 1 2 1 1 0 2 0 7 0.3
 C56 183–183.9 Ovary 8 9 15 10 8 9 11 6 4 0 80 3.4
 C64 189–189.1 Kidney 1 0 0 3 0 1 7 1 3 0 16 0.7
 C65-67 189.2–189.4 Urothelial tract 0 0 2 1 4 1 2 0 0 0 10 0.4
 C82-85 200–200.9 Non-Hodgkin's 1 2 4 8 9 9 3 6 4 1 47 2.0
202–202.9
 C90 203–203.8 Multiple myeloma 0 1 3 4 4 5 8 4 1 0 30 1.3
 C92 205–205.9 Myeloid leukemia 2 5 3 4 4 6 1 2 0 0 27 1.2
 E00-E89 240–279.9 Endocrine, nutritional and metabolic diseases 2 4 5 12 18 20 37 29 15 3 145 1.6
 G00-G99 330–359.9 Diseases of the nervous system 3 2 8 4 11 13 9 12 4 0 66 0.7
 I00-I99 390–459.9 Diseases of the circulatory system 33 65 112 171 322 543 753 780 600 343 3722 41.0
 I20-I25 410–414.9 Ischemic heart disease 4 9 24 39 73 127 134 123 89 32 654
 I48 427.3 Atrial fibrillation and flutter 0 0 0 2 0 3 7 8 2 1 23
 I50 428–428.9 Heart failure 9 8 20 28 71 124 164 218 173 118 933
 I60-69 430–438.9 Cerebrovascular disease 12 33 50 81 130 218 335 337 251 150 1597
 I71 441–441.9 Aortic aneurysm and dissection 1 1 0 1 5 8 12 8 2 0 38
 J00-J99 460–519.9 Diseases of the respiratory system 7 12 20 47 81 111 197 221 138 75 909 10.0
 J10-J18 480–487.9 Influenza 1 4 8 25 44 72 133 149 98 67 601
 J43 492 Emphysema 0 0 0 1 2 1 1 4 3 2 14
 K00-K93 520–579.9 Diseases of the digestive system 9 9 24 39 38 62 68 68 54 26 397 4.4
 K74 571.5–571.6 Fibrosis and cirrhosis of liver 5 5 10 18 17 22 22 10 2 0 111
 N00-N99 580–629.9 Diseases of the genitourinary system 3 3 9 19 23 45 65 52 43 17 279 3.1
 N17-N19 584–586 Acute kidney failure and chronic kidney disease 3 3 8 17 18 33 50 38 29 16 215
 R00-R99 780–799.9 Symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified 2 3 2 11 11 33 51 109 119 141 482 5.3
 R54 797 Age-related physical debility 0 0 0 0 2 16 28 87 112 130 375
 S00-T88 800–999.9 External causes 11 18 15 31 50 52 46 26 21 11 281 3.1
Others 7 8 19 18 31 45 44 40 27 12 251 2.8

Discussion

The Three-Prefecture Cohort Study, which had approximately 100,000 participants with consecutive follow-up for up to 15 years and a 90% response rate to the baseline questionnaire survey regarding participants' lifestyles, was one of the largest representative prospective, population-based cohort studies in Japan. The study areas were selected because they contained national air monitoring stations and the community-based cancer registry was conducted actively; this large-scale observation enabled us to determine not only all-cause mortality but also cancer incidence among community residents. The association of air pollution and lung cancer mortality was reported previously.6 This report briefly describes the characteristics (e.g., smoking status, alcohol drinking status, and type of occupation) and endpoints among study participants by gender.

This study had several strengths. First, more than 100,000 participants answered a baseline questionnaire survey, and the response rate was approximately 90%. This response rate was similar to those of the JACC Study, which was launched in the mid-1980s,1 and the JPHC Study, which was launched in the 1990s.2 Many cohort studies in Japan have focused on residents in rural areas in order to conduct long-term follow-up.1, 2 However, since this study included both urban and rural areas, findings from this cohort may help to evaluate the relationship between lifestyles and various diseases, irrespective of area. This study population was similar to the general population in cancer and mortality risks, with SIR and SMR close to 1.0.11, 12 Considering the large sample size, the high questionnaire response rate, and adequate regional balance, we consider that the association between participants' lifestyles and endpoints measured in this study is generalizable to the whole population of Japan. Second, in contrast to other large-scale cohorts in Japan, the collection of detailed information on participants' occupation, such as the longest period of employment, is another strength of this study, and we will address the association between occupation and incidence and mortality of non-communicable diseases in the future using this cohort data. Third, the use of community-based cancer incidence data from a cohort of 100,000 participants was also a strength of this study, because there are few available analyses of cancer incidence data from large-scale cohort studies in Japan. Fourth, this cohort can be pooled with other large-scale cohorts in Japan (e.g., the JACC Study,1 the JPHC Study,2 or the Ohsaki Cohort13) and serve to provide new findings from Japan.

This study has several limitations. First, this registry was launched in the 1980s and its follow-up of participants was completed in 2000. The associations between participants' lifestyles and endpoints might differ from those since 2000, because lifestyles diversify with the times. Second, in cohort studies, non-questionnaire responders had more unfavorable lifestyles than responders2, 14, 15, 16 and were less likely to join the health check-ups.2 However, the overall response rate in this cohort was almost 90%, and we consider that the impact of differences between responders in cities and those in towns would be small. Furthermore, the numbers of delivered questionnaires in Sendai City and Osaka City were fewer than those in other cities/towns, because residents' local organizations did not cover the entire community and could not deliver questionnaires in the whole region. Therefore, the representativeness would be weaker in these areas than in other areas. Third, we could not evaluate the energy intake or nutrient consumption of participants because the Three-Prefecture Cohort Study used a food frequency questionnaire with a small number of items.

Conclusions

The Three-Prefecture Cohort Study was conducted from the 1980s to 2000 and is one of the largest representative prospective population-based cohort studies in Japan. This study enabled us to reveal the association of multiphasic lifestyle factors with cancer incidence and mortality in a single cohort. It will also allow us to conduct a pooled analysis in combination with other large-scale cohorts, which will be of considerable help in gaining insights into the epidemiology of non-communicable diseases in Japan.

Conflicts of interest

None declared.

Acknowledgments

We sincerely thank the staff within each study area for their collection and processing of data. We also express our gratitude to all the participants of the study. This study was supported via a Grant-in-Aid for Scientific Research (25460752) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Footnotes

Peer review under responsibility of the Japan Epidemiological Association.

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