Lower risk of death from gastric cancer among participants of gastric cancer screening in Japan: A population-based cohort study

Preventive Medicine 44 (2007) 12 – 19 www.elsevier.com/locate/ypmed

Lower risk of death from gastric cancer among participants of gastric cancer screening in Japan: A population-based cohort study Akira Miyamoto a,b,⁎, Shinichi Kuriyama a , Yoshikazu Nishino a , Yoshitaka Tsubono a , Naoki Nakaya a , Kaori Ohmori a , Kayoko Kurashima a , Daisuke Shibuya c , Ichiro Tsuji a a

Division of Epidemiology, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryou-machi, Aoba-ku, Sendai, 980-8575, Japan b Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Japan c Miyagi Cancer Society, Japan Available online 7 September 2006

Abstract Objective. This study aimed to investigate the association between gastric cancer screening and mortality from gastric cancer. Methods. In 1990, 47,605 Japanese subjects were recruited and completed a questionnaire about participation in gastric cancer screening and lifestyle. We followed up their vital status through December 2001. In this cohort, 41,394 subjects without a history of cancer were allocated to the screened group or the unscreened group according to their response to the question about gastric cancer screening. We estimated the relative risk (RR) of death from gastric cancer, death from any cause except gastric cancer, and incidence of gastric cancer with adjustment for potential confounding variables. Results. The risk of death from gastric cancer among the screened group was significantly lower than that among the unscreened group. The multivariate RR of death from gastric cancer for screened individuals compared with those not screened was 0.54 (95% confidence interval [CI]: 0.38, 0.77). The RR of death from any cause except gastric cancer was 0.83 (95% CI: 0.77, 0.90), and the RR of incidence of gastric cancer was 0.94 (95% CI: 0.79, 1.13). Conclusion. Our data suggest that gastric cancer screening or factors associated with it may be associated with lower mortality from gastric cancer. © 2006 Published by Elsevier Inc. Keywords: Gastric cancer; Gastric cancer screening; Cohort study; Japanese

Introduction Gastric cancer is the second largest cause of cancer death in Japan. Recently, both the incidence and mortality of gastric cancer have been decreasing (Statistics and information department, minister's secretariat, ministry of health, labor and welfare, 1952–2001). From 1975 to 1998, the age-adjusted incidence of gastric cancer (per 100,000 persons) decreased by 27.0% from 119.3 for men and by 40.1% from 56.3 for women. From 1975 to 1998, the age-adjusted mortality due to gastric cancer decreased by 47.0% from 79.4 for men and by 58.8% from 39.8 for women (Statistics and information department, minister's secretariat, ministry of health, labor and welfare, ⁎ Corresponding author. Fax: +81 22 717 8125. E-mail address: [email protected] (A. Miyamoto). 0091-7435/$ - see front matter © 2006 Published by Elsevier Inc. doi:10.1016/j.ypmed.2006.07.016

1952–2001; The Japanese Society of Gastroenterological Mass Survey, 1985, 1991, 2000). The degree of decrease was more marked in mortality than in incidence. The discrepancy between mortality reduction and incidence reduction could be attributable to the widespread adoption of gastric cancer screening (The Japanese Society of Gastroenterological Mass Survey, 1985, 1991, 2000; Hisamichi, 1983). Screening for gastric cancer started in 1960 in Japan. The Law for Health of the Aged required every municipality to conduct screening for gastric cancer among residents aged 40 years and over. At present, about 5.8 million people, about 9.2% of all persons aged 40 years and over, participate in gastric cancer screening annually in Japan (Committee of National Statistics, 1999; Statistics and information department, minister's secretariat, ministry of health, labor and welfare, 2001).

A. Miyamoto et al. / Preventive Medicine 44 (2007) 12–19

Three case–control studies and five cohort studies have been conducted to estimate the effect of gastric cancer screening in Japan on gastric cancer mortality. All case–control studies agreed that such screening was effective (Oshima et al., 1986; Fukao et al., 1995a,b; Abe et al., 1995). Three cohort studies did not demonstrate any effectiveness of screening (Oshima et al., 1979; Inaba et al., 1999; Mizoue et al., 2003). Two cohort studies demonstrated screening effectiveness (Hisamichi and Sugawara, 1984; Lee et al., 2005), and one of them did not take into account the effect of health-related lifestyle factors such as smoking, alcohol consumption, and nutrition (Hisamichi and Sugawara, 1984). Table 1 summarizes the five cohort studies, the results of which were inconsistent. The discrepancy was thought to result from a lack of statistical power (Oshima et al., 1979; Inaba et al., 1999) or potential selection bias (Mizoue et al., 2003; Hisamichi and Sugawara, 1984).

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The ideal design for evaluating the effectiveness of cancer screenings is a randomized controlled trial (RCT). However, it is not ethical in Japan to conduct a RCT of gastric cancer screening, as it has already been implemented by law. On the other hand, the findings of case–control studies are subject to various biases, including recall bias (Hosek et al., 1996). Therefore, we conducted a cohort study to investigate the effect of gastric cancer screening on mortality in the Japanese general population, considering gastric cancer incidence and death from any cause except gastric cancer. Subjects and methods Screening for gastric cancer in Japan The most common method of gastric cancer screening is photofluorography. According to the standardized procedure proposed by the Japanese Society for Gastroenterological Mass Survey, seven consecutive photofluorograms,

Table 1 Summary of cohort studies of gastric cancer screening by photofluorography Author

Oshima

Hisamihi

Study population

Osaka Prefecture

Miyagi Prefecture

Follow-up

1967–1975 (6 years)

1960–1977 (18 years)

Age

No. of subjects

All age ∼ 39 years 40–59 years 60–69 years 70– years

9927 18,785 3330 747

40–69 years Men Screened Unscreened Women Screened Unscreened

No. of gastric cancers

Results

Incidence

O/E ratio

Death

Incidence

Mortality rate

335 20 182 105 28

179 6 78 71 24

1.37 1.46 1.35 1.44 1.27

0.91 0.63 0.74 1.13 1.19

2098 1287

74 44

25 30

187.7 201.8 NS

61.9 137.2 P < 0.005

2227 1396

29 18

14 12

58.1 79.1 NS

28.1 53.8 P < 0.01

RR(95% CI) Inaba

Mizoue

Lee

Gifu Prefecture

JACC study

JPHC study

1992–1995 (40 months)

1988–1997 (8 years)

1990–2003 (13 years)

Over 40 years Men Screened Unscreened Women Screened Unscreened 50–69 years Men Screened Unscreened Women Screened Unscreened 40–59 years Over all Screened Unscreened

O/E, Observed/Expected; NS, not significant; CI, confidence interval; RR, relative risk.

4934 6536

8 19

0.72 (0.31–1.66) 1

4208 8456

4 9

1.46 (0.43–4.90) 1

12,999 23,156

78 244

0.65 (0.45–0.95) 1

17,772 33,385

45 113

0.75 (0.42–1.34) 1

49 130

0.52 (0.36–0.74) 1

42,150 36% 64%

262 374

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A. Miyamoto et al. / Preventive Medicine 44 (2007) 12–19

covering the whole area of the stomach, are taken (Committee of Photofluorography, 1984). The photofluorograms are taken by radiographic technicians using effervescent granules without hypotonic agents, and the films are read by two radiologists independently. Any screenee with a suspected abnormality is referred for further diagnostic examinations including endoscopy and biopsy.

Study cohort Miyagi Prefecture, which had a population of 2,359,991 in 2003, is the economic and cultural center of north-eastern Japan, and the main industry is agriculture. We have reported the design of this cohort study in detail elsewhere (Fukao et al., 1986; Tsubono et al., 2001a,b). Briefly, we delivered a selfadministered questionnaire to all residents (n = 51,921) aged 40–64 years in 14 municipalities of Miyagi Prefecture from June through August 1990. The questionnaire asked about demographic variables, personal, and family histories of cancer and other diseases, and health-related lifestyle including smoking, alcohol use, diet, and use of cancer screening. Responses to the questionnaire were received from 47,605 subjects (22,836 men and 24,769 women). The study protocol was approved by the Institutional Review Board of Tohoku University School of Medicine.

Exposure data There were two questions about gastric cancer screening in the baseline questionnaire: “Did you take gastric cancer screening in the past year?” and “How many times did you take the gastric cancer screening during the previous five years?” We allocated the subjects to the screened group and the unscreened group on the basis of their answers to the first question, to avoid any healthy screenee bias created by dependency of participation upon the health status of the subjects (Hosek et al., 1996; Berrino et al., 1984; Morrison, 1985; Friedman and Dubin, 1991; Cronin et al., 1998; Tsuji et al., 1999).

Statistical analysis We used the Cox proportional hazards regression method to estimate the relative risk (RR) of incident gastric cancer, death from gastric cancer, and death from any cause except gastric cancer, respectively, with adjustment for age, sex, and other potential confounding variables (Rothman and Greenland, 1998). The relative risk of death from any cause except gastric cancer was analyzed in order to measure the magnitude of potential selection bias. In addition to age and sex, we considered the following variables as potential confounders: active cigarette smoking (never smoked, smoked in the past, currently smoking 1–19 cigarettes per day, or currently smoking ≥20 cigarettes per day), drinking habit (never, past, current), family history of gastric cancer, educational background (in school until age 15 years or younger, age 16–18 years, or age 19 years or older), BMI (< 18.5, 18.5–25, 25≤), walking (<30 min/day, 30 min–1 h/day, ≥1 h/day), consumption frequency of various foods (spinach, carrot, orange, other fruit, tsukemono, beef, milk, dried fish and salted fish: every day, 3–4 times per week, 1–2 times per week, 1–2 times per month, never), consumption frequency of green tea and coffee (never, rarely, 1–2 cups per day, 3–4 cups per day, ≥5 cups per day), type of health insurance (four main types), and history of screening for other diseases (lung cancer screening and cardiovascular disease screening) (Fukao et al., 1992; Ogawa et al., 1985; Yatsuya et al., 2002). Tsukemono is pickled vegetables, which are salted for preservation. There is some evidence that salted or pickled foods are associated with a higher risk of gastric cancer (Howson et al., 1986; Ye et al., 1998; Ward and Lopez-Carrillo, 1999; Kim et al., 2002; Lee et al., 2003; Tsugane et al., 2004), whereas intake of fresh vegetables and fruit is associated with a lower risk of gastric cancer (Tsubono et al., 1997; Ngoan et al., 2002; Sauvaget et al., 2003). There was no association between green tea consumption and the risk of gastric cancer (Tsubono et al., 2001a,b; Hoshiyama et al., 2002; Koizumi et al., 2003; Hoshiyama et al., 2004). All statistical analyses were performed using SAS software, version 9.1 (SAS/STAT software, 2004). All statistical tests were two-tailed.

Results Follow-up Of the 47,605 subjects who responded to the questionnaire, we excluded 6211 subjects, 1113 of whom had histories of cancer and 5098 of whom did not respond to the question about gastric cancer screening. Consequently, 41,394 subjects (20,093 men and 21,301 women) remained for the analysis, giving a response rate of 79.7%. We used population registries in the 14 municipalities to ascertain the vital and residential status of the subjects from June 1, 1990 through December 31, 2001. We identified incident cases of gastric cancer by computerized record linkage with the Miyagi Prefectural Cancer Registry (Takano and Okuno, 1997), established in 1959, which is one of the oldest and most accurate regional cancer registries in Japan. We obtained data on cancer incidence, including site of cancer, clinical stage, and histological type, from the registry records. The rate of death certificate only (DCO) was 15.0% in 2000. We obtained information on the date and cause of death by reviewing the death certificates of the subjects at the public health center in the study area. We obtained information on emigration from the municipalities every year. Emigrants were lost to follow-up at the time of emigration because we were unable to obtain the new addresses. In the mortality analysis, we counted person-years of follow-up for each subject from June 1, 1990 until the date of death, date of migration outside the study districts, or the end of the study period (December 31, 2001), whichever occurred first. A total of 1088 subjects (3.7%) were lost to follow-up during the study period and 456,577 person-years were accumulated. Over the follow-up period, 152 deaths from gastric cancer and 2800 deaths from any cause except gastric cancer were identified. In the incidence analysis, we counted person-years of follow-up for each subject from June 1, 1990 until the date of diagnosis of gastric cancer, date of death, date of migration outside the study districts, or the end of the study period (December 31, 2001), whichever occurred first, and 454,516 person-years were accumulated. Over the follow-up period, 585 incident cases of gastric cancer were identified.

Table 2 presents the characteristics of subjects in the screened group and the unscreened group at the baseline. The screened group tended to be older, to smoke less, to have more family history of gastric cancer, to have longer educational history, and to take more exercise than the unscreened group. There was no apparent difference in BMI between the two groups. The risk of incident gastric cancer did not differ between the screened group and the unscreened group overall, or for men or for women. The multivariate relative risk (RR) and 95% confidence interval (CI) of the screened group overall was 0.94 (95% CI: 0.79, 1.13) compared to the unscreened group, 0.98 (95% CI: 0.78, 1.22) for men and 0.91 (95% CI: 0.65, 1.25) for women (Table 3). The risk of gastric cancer mortality was significantly lower in the screened group than in the unscreened group overall, and also for men and for women. The multivariate RR of the screened group for deaths from gastric cancer compared to the unscreened group was 0.54 (95% CI: 0.38, 0.77) overall, 0.62 (95% CI: 0.41, 0.93) for men and 0.43 (95% CI: 0.22, 0.87) for women (Table 3). The risk of death due to any cause except gastric cancer was also significantly lower in the screened group than in the unscreened group overall, and also for men and for women. However, the reduction of risk was larger for mortality from gastric cancer than for mortality from any cause except gastric cancer. The multivariate RR of the screened group compared to the unscreened group was 0.83 (95% CI: 0.77, 0.90) overall,

A. Miyamoto et al. / Preventive Medicine 44 (2007) 12–19

0.87 (95% CI: 0.78, 0.96) for men and 0.76 (95% CI: 0.66, 0.88) for women (Table 3). The proportion of early gastric cancer was higher among the screened group (44.7%) than among the unscreened group (28.6%). The proportion of incident gastric cancer cases detected during 3 years from the baseline was 25.2% for the unscreened group and 22.3% for the screened group. The difference between the two groups was not significant. Among 1113 subjects with a self-reported history of cancer, 315 had gastric cancer. We analyzed the mortality from gastric cancer without excluding these subjects. Multivariate RR and 95% CI were 0.62 (95% CI: 0.45, 0.87). For cases resulting in death, the average duration of the illness was 304.6 days for the unscreened group, and 379.9 days for the screened group. Discussion In this cohort study, we investigated the effectiveness of gastric cancer screening on the reduction of mortality due to gastric cancer in Japan. The risk of death from gastric cancer among the screened group was significantly lower than that among the unscreened group. In general, screening does not affect the incidence of gastric cancer, and the incidence reduction is directly related to the reduction in mortality. However, this mortality reduction would not be attributable to the incidence reduction because gastric cancer incidence did not differ between the screened group and the unscreened group. On the other hand, participation in gastric cancer screening would also be associated with other healthy lifestyle behaviors that could lower mortality. In fact, the multivariate RR of death from any cause except gastric cancer was 17% lower among the screened group; 0.83 (95% CI: 0.77, 0.90). However, the risk difference for gastric cancer mortality was larger (46%); 0.54 (95% CI: 0.38, 0.77). Although the risk of gastric cancer incidence did not differ between the screened group and the unscreened group, the proportion of early gastric cancer was higher among the former than among the latter. For cases resulting in death, the average duration of the illness was longer in the screened group than in the unscreened group, although this would have been partly attributable to lead-time bias. Therefore, the reduction in gastric cancer mortality among the screened group cannot be explained by the effects of a healthier lifestyle alone. Our study had several methodological advantages over previous cohort studies of gastric cancer screening and the risk of gastric cancer mortality. Firstly, we recruited subjects from the general population, followed up a relatively large number of subjects (n = 41,394) over an 11-year period, and identified relatively many cases of gastric cancer. Three of the previous cohort studies did not show a significant mortality reduction effect (Oshima et al., 1979; Inaba et al., 1999; Mizoue et al., 2003). Two of these studies had a smaller sample size (Oshima et al., 1979) or a shorter follow-up period (Inaba et al., 1999). Secondly, we investigated the risk of incident gastric cancer in order to examine whether decreased mortality would be due

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Table 2 Characteristics of study subjects, Miyagi Prefecture, Japan in 1990 Men

Women

Unscreened Screened

Unscreened Screened

No. of subjects 8177 Mean age 50.33 Family history of gastric Yes 7.77 No 92.23 Smoking habit (%) Never 17.67 Past 17.75 Current 1–19/day 15.83 20≦/day 48.75 Drinking habit (%) Never 16.59 Past 7.16 Current 1 > go/day 22.16 1–2 go/day 17.39 2–3 go/day 21.55 3 > go/day 15.15 Education (year of age) (%) ≦15 43.39 16–18 44.78 19 ≦ 11.83 Health insurance (%) Persons who were self58.18 employed or retired Employees of small 5.61 companies Government employees 23.77 Employees of medium9.01 sized and large companies Other, minor plans 3.42 Screening (%) Cardiovascular disease screening Screened 63.60 Unscreened 36.40 Tuberculosis/lung cancer screening Screened 83.29 Unscreened 16.71 BMI <18.5 2.16 18.5–25 70.54 25 ≤ 27.31 Walking ≧1 h/day 46.70 30 min–1 h/day 20.86 − 30 min/day 32.44 Dietary habits (%) Beef consumption Everyday 0.63 3–4 times/week 1.93 1–2 times/week 12.62 1–2 times/month 42.14 Never 42.68 Pork consumption Everyday 3.29 3–4 times/week 17.94 1–2 times/week 47.78 1–2 times/month 24.45 Never 6.54

11,916 9203 52.33 50.43

12,098 53.2

11.87 88.13

8.51 91.49

13.69 86.31

20.59 22.94

88.33 1.97

90.84 2.07

14.62 41.85

6.53 3.17

5.27 1.81

15.05 7.08

70.33 4.39

73.34 3.58

24.59 19.46 22.16 11.67

21.86 2.07 0.85 0.50

20.42 1.72 0.67 0.27

37.60 46.06 16.34

39.29 48.84 11.86

38.91 47.21 13.89

47.69

49.86

50.57

13.16

7.95

9.41

23.02 13.92

26.54 10.93

23.65 13.00

2.21

4.72

3.37

91.96 8.04

62.66 37.34

89.64 10.36

97.46 2.54

87.62 12.38

97.56 2.44

1.80 70.28 27.92

3.01 65.34 31.65

2.35 66.90 30.75

43.61 26.08 30.31

44.13 24.67 31.20

46.39 25.07 28.54

0.63 2.19 13.49 45.54 38.15

0.47 1.24 9.41 33.87 55.02

0.60 1.41 10.70 36.49 50.80

2.40 17.06 49.50 25.29 5.75

2.99 19.79 48.71 19.37 9.14

2.79 20.30 49.81 19.34 7.77

(continued on next pages)

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A. Miyamoto et al. / Preventive Medicine 44 (2007) 12–19

Table 22 (continued) (continued) Table

Dietary habits (%) Milk consumption Everyday 3–4 times/week 1–2 times/week 1–2 times/month Never Fry and tempura consumption Everyday 3–4 times/week 1–2 times/week 1–2 times/month Never Fresh fish consumption Everyday 3–4 times/week 1–2 times/week 1–2 times/month Never Dried fish and salted fish consumption Everyday 3–4 times/week 1–2 times/week 1–2 times/month Never Spinach consumption Everyday 3–4 times/week 1–2 times/week 1–2 times/month Never Carrot consumption Everyday 3–4 times/week 1–2 times/week 1–2 times/month Never Tsukemono consumption Everyday 3–4 times/week 1–2 times/week 1–2 times/month Never Orange consumption Everyday 3–4 times/week 1–2 times/week 1–2 times/month Never Other fruit consumption Everyday 3–4 times/week 1–2 times/week 1–2 times/month Never Coffee consumption ≧5 cups/day 3–4 cups/day 1–2 cups/day Sometimes Never

Table 2 (continued) Men

Women

Unscreened Screened

Unscreened Screened

38.73 15.93 17.06 11.29 16.99

48.66 16.22 15.14 8.16 11.82

45.86 16.42 14.48 6.99 16.26

57.13 15.40 11.69 5.39 10.39

3.47 15.56 48.82 28.84 3.32

2.98 16.00 50.02 28.20 2.80

3.08 15.69 49.84 28.71 2.66

2.72 16.10 51.75 27.05 2.38

31.10 32.59 29.24 6.30 0.77

31.88 34.08 28.18 5.06 0.80

30.26 36.04 27.36 5.06 1.27

34.89 36.26 23.79 4.05 1.01

7.75 17.38 37.84 28.55 8.48

6.76 16.39 40.75 28.85 7.25

7.03 17.86 40.44 27.83 6.85

8.07 18.72 40.85 25.74 6.62

18.42 28.66 36.43 13.75 2.74

21.76 30.79 33.76 11.60 2.09

23.45 34.91 31.56 8.68 1.40

29.44 35.87 27.69 6.03 0.97

8.81 22.48 38.43 23.49 6.79

9.87 24.62 39.33 21.78 4.40

17.00 33.59 35.87 11.78 1.75

20.93 36.55 31.99 9.36 1.16

55.26 19.43 14.37 6.20 4.73

55.13 20.78 14.09 5.59 4.41

63.97 17.34 11.37 3.92 3.41

65.54 16.75 11.00 3.87 2.85

17.56 22.14 28.39 22.68 9.24

18.08 23.92 30.62 20.87 6.51

36.01 26.98 20.86 11.82 4.33

37.27 27.22 20.63 11.63 3.25

19.33 26.12 31.05 17.29 6.21

23.04 28.95 30.61 13.39 4.00

39.86 30.17 20.23 7.39 2.35

44.27 30.12 18.45 5.67 1.49

17.88 33.23 30.87 12.22 5.80

16.76 36.17 31.41 11.11 4.55

17.37 34.57 35.49 9.30 3.28

19.48 39.97 31.96 6.70 1.90

Dietary habits (%) Green tea consumption ≧5 cups/day 3–4 cups/day 1–2 cups/day Sometimes Never

Men

Women

Unscreened Screened

Unscreened Screened

24.46 19.86 22.97 20.78 11.93

25.93 22.44 24.59 17.70 9.34

25.71 21.30 23.82 20.14 9.03

26.52 22.88 22.82 19.88 7.90

to decreased cancer incidence. If the incidence of gastric cancer had been lower in the screened group, then the mortality in the screened group would also have become lower (Fukao et al., 1986). Therefore, we should compare the risk of incident gastric cancer between the screened and the unscreened groups. However, the previous two cohort studies did not investigate the incidence of gastric cancer (Inaba et al., 1999; Mizoue et al., 2003). Thirdly, we analyzed the effect of gastric cancer screening upon mortality after adjustment for various potentially confounding variables such as smoking, dietary habits, and other lifestyle-related behaviors, but two of the previous cohort studies did not adjust for confounding variables (Oshima et al., 1979; Hisamichi and Sugawara, 1984). We assessed the history of gastric cancer screening and other variables before cases of gastric cancer and death were identified, thus avoiding recall bias. Fourthly, the data from the cancer registry we used were reasonably accurate. The rate of DCO for the Miyagi Cancer Registry in 2000 was 15.0%, which was the fourth lowest among all the prefectures in Japan. Our study also had some limitations. First, the present study was an observational study, not a RCT. Observational studies have inevitable limitations such as selection bias in recruitment and the effect of unknown confounders. The risk of death from any cause except gastric cancer was significantly lower among the screened group. Individuals in the screened group may have better control of their disease than unscreened individuals. They may have a better social network and higher socioeconomic status, as participating in health screening is one activity through which they take part in society (Suarez et al., 1994; Kang and Bloom, 1993; Segnan, 1997; Lucina et al., 2000; Husaini et al., 2001; Kang et al., 1994). These factors might explain the difference in the risk of death from any cause except gastric cancer between the two groups. Secondly, screening status was based on self-administered questionnaires, and whether or not the subjects participated in screening after the baseline was unknown. Some misclassification of screening status would arise when estimating the effect of screening. In fact, the proportion of cases that had been identified by the screening in each group resulted in 19.4% for the unscreened, and 38.1% for the screened. However, Lee et al. reported that about 60% of subjects who attended gastric cancer screening at the baseline continued to do so during the first five years. The respective proportion among those unscreened was 75% (Lee et al., 2005). This finding suggests that a single

A. Miyamoto et al. / Preventive Medicine 44 (2007) 12–19 Table 3 Relative risks (RRs) and their 95% confidence intervals (CIs) of gastric cancer incidence, gastric cancer death, and death from non-gastric cancer according to gastric cancer screening, Miyagi Prefecture, Japan, 1990–2001 Unscreened

Screened

Gastric cancer incidence Over-all Person-years No. of gastric cancer Age-adjusted RR (95% CI) Multivariate RR1 a (95% CI) Multivariate RR2 b (95% CI) Men Person-years No. of gastric cancer Age-adjusted RR (95% CI) Multivariate RR1 a (95% CI) Multivariate RR2 b (95% CI) Women Person-years No. of gastric cancer Age-adjusted RR (95% CI) Multivariate RR1 a (95% CI) Multivariate RR2 b (95% CI)

17,380 190,372 222 1.00 (referent) 1.00 (referent) 1.00 (referent) 8177 88,944 150 1.00 (referent) 1.00 (referent) 1.00 (referent) 9203 101,429 72 1.00 (referent) 1.00 (referent) 1.00 (referent)

24,014 264,144 363 0.99 (0.83, 1.17) 0.95 (0.80, 1.13) 0.94 (0.79, 1.13) 11,916 129,437 255 0.99 (0.81, 1.21) 0.99 (0.81, 1.22) 0.98 (0.78, 1.22) 12,098 134,707 108 0.96 (0.71, 1.30) 0.91 (0.67, 1.24) 0.91 (0.65, 1.25)

Gastric cancer death Over-all Person-years No. of death Age-adjusted RR (95% CI) Multivariate RR1 a (95% CI) Multivariate RR2 b (95% CI) Men Person-years No. of death Age-adjusted RR (95% CI) Multivariate RR1 a (95% CI) Multivariate RR2 b (95% CI) Women Person-years No. of death Age-adjusted RR (95% CI) Multivariate RR1 a (95% CI) Multivariate RR2 b (95% CI)

17,380 190,974 82 1.00 (referent) 1.00 (referent) 1.00 (referent) 8177 89,331 59 1.00 (referent) 1.00 (referent) 1.00 (referent) 9203 101,643 23 1.00 (referent) 1.00 (referent) 1.00 (referent)

24,014 265,603 70 0.52 (0.38, 0.72) 0.50 (0.36, 0.69) 0.54 (0.38, 0.77) 11,916 130,428 53 0.52 (0.36, 0.75) 0.52 (0.36, 0.77) 0.62 (0.41, 0.93) 12,098 135,175 17 0.51 (0.27, 0.96) 0.48 ( 0.25, 0.91 ) 0.43 (0.22, 0.87)

Death from non-gastric cancer Over-all Person-years No. of death Age-adjusted RR (95% CI) Multivariate RR1 a (95% CI) Multivariate RR2 b (95% CI) Men Person-years No. of death Age-adjusted RR (95% CI) Multivariate RR1 a (95% CI) Multivariate RR2 b (95% CI) Women Person-years No. of death Age-adjusted RR (95% CI) Multivariate RR1 a (95% CI) Multivariate RR2 b (95% CI)

17,380 190,974 1209 1.00 (referent) 1.00 (referent) 1.00 (referent) 8177 89,331 785 1.00 (referent) 1.00 (referent) 1.00 (referent) 9203 101,643 424 1.00 (referent) 1.00 (referent) 1.00 (referent)

24,014 265,603 1591 0.78 (0.72, 0.84) 0.80 (0.75, 0.87) 0.83 (0.77, 0.90) 11,916 130,428 1080 0.79 (0.72, 0.87) 0.84 (0.76, 0.92) 0.87 (0.78, 0.96) 12,098 135,175 511 0.73 (0.64, 0.83) 0.75 (0.66, 0.85) 0.76 (0.66, 0.88)

Notes to Table 3:

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participation in screening can be a predictor of future participation. Furthermore, this misclassification is non-differential and would tend to lead to underestimation of the effectiveness of screening. Thirdly, we excluded 6211 subjects because they did not answer the question on gastric cancer screening (5098) or because they had a self-reported history of cancer (1113). Ninety-eight cases of gastric cancer were diagnosed in this group. The three groups, the excluded group, the screened group, and the unscreened group, were similar with respect to gender (45.3%, 49.4%, and 46.8% were men), mean age (54.4, 52.9 and 50.4 years old), and the prevalence of current smokers (30.5%, 30.7%, and 34.5%) and current alcohol drinkers (38.1%, 48.0%, and 47.4%). The incidence of gastric cancer did not differ among the groups. The multivariate RR (95% CI) of incident gastric cancer in the excluded group, compared to the unscreened group, was 1.09 (95% CI: 0.82, 1.46). The multivariate RR (95% CI) of incident gastric cancer in the screened group, compared to the unscreened group, was 0.97 (95% CI: 0.81, 1.15). We also conducted a sensitivity analysis. If the excluded group were assumed the screened group, the multivariate RR (95% CI) of incident gastric cancer and of death from gastric cancer would be 1.00 (95% CI: 0.84, 1.19) and 0.70 (95% CI: 0.52, 0.95), respectively. If the excluded group were assumed the unscreened group, the multivariate RR (95%CI) of incident gastric cancer and of death from gastric cancer would be 0.97 (95% CI: 0.82, 1.14) and 0.63(95% CI: 0.47, 0.86), respectively. Thus, our result would not be substantially biased by exclusion of the subjects who did not answer the question on gastric cancer screening or had cancer history. The proportion of incident gastric cancer cases that were detected during the three years from the baseline was 25.2% for the unscreened group and 22.3% for the screened group. Furthermore, after including 315 previous cases of gastric cancer, the multivariate RR2 of death from gastric cancer was not changed substantially; 0.62 (95% CI: 0.45, 0.87). Thus, the effect of screening before the baseline survey would not have been large. The rate of participation in the gastric cancer screening for the study subjects (58.0%) was higher than the national average (9.2%) (Committee of National Statistics, 1999; Statistics and information department, minister's secretariat, ministry of health, labor and welfare, 2001). Therefore, caution may be needed when extrapolating our results to other areas where the participation rate is lower. Notes to Table 3: a Adjusted for age in years; family history of gastric cancer, cigarette smoking, alcohol drinking, BMI, the sort of health insurance, walk, consumption frequencies of green tea, tsukemono, dried fish and salted fish. b Adjusted for age in years; family history of gastric cancer, cigarette smoking, alcohol drinking, BMI, the sort of health insurance, walk, educational background, other screenings (tuberculosis or lung cancer screening, cardiovascular disease screening), consumption frequencies of green tea, coffee, tsukemono, dried fish and salted fish, beef, spinach, carrot, orange, other fruit, milk.

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