Japanese Journal of Clinical Oncology 32:284-290 (2002)
© 2002 Foundation for Promotion of Cancer Research
Risk Factors for Stomach Cancer in Brazil (II): a Case-control Study among Japanese Brazilians in São Paulo
1 Nikkei Disease Prevention Center, Santa Cruz Hospital, São Paulo, 2 Department of Head and Neck Surgery and 3 Research Center, A. C. Camargo Hospital, São Paulo, 4 Department of Gastroenterology and 5 Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil and 6 Epidemiology and Biostatistics Division, National Cancer Center Research Institute East, Kashiwa, Chiba, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONAcknowledgmentsStudy Group MembersREFERENCES |
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Background: Although stomach cancer is the most frequent cancer among Japanese Brazilians, the risk factor of this cancer has not been investigated among them.
Methods: A case-control study was conducted among Japanese residents in the city of São Paulo. Ninety-six consecutive cases of histologically confirmed stomach cancer were matched to 192 controls admitted for non-neoplastic diseases or healthy volunteer (n = 80) by age (±5 years) and gender. The socio-demographic characteristics, personal and family medical history, lifetime history of tobacco use and dietary habits were probed using a structured questionnaire.
Results: Frequent consumption of beef was associated with increased risk: odds ratio (OR) = 4.0 and 95% confidence interval (CI) = 1.9–8.4 for daily consumption, OR = 2.1 and 95% CI = 1.0–4.3 for 3–4 days/week) when compared with the category of lower consumption (<3 days/week) after adjustment for country of birth (Japan or Brazil), showing a dose–response pattern (P for trend = 0.001). These ORs became higher after further adjusted for fruit consumption: OR = 4.4, 95% CI = 2.1–9.4 and OR = 2.4 and 95% CI = 1.1–5.0, respectively. Daily consumption of fruit was associated with a reduction in risk (OR = 0.5, 95% CI = 0.3–1.0) after adjustment for country of birth and became statistically significant further adjusted for beef consumption (OR = 0.4, 95% CI = 0.2–0.9). There were no statistically significant associations with smoking or any other factors tested. Although some attenuation was observed in beef consumption, the observed associations were similar after excluding volunteer controls.
Conclusions: The introduction of the habit of daily beef consumption among Japanese immigrants and their descendants may be associated with stomach cancer risk. The protective effect of fruit consumption was confirmed in this population.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONAcknowledgmentsStudy Group MembersREFERENCES |
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Japanese immigrant residents in the city of São Paulo, Brazil, remain at a high risk of developing stomach cancer, with only a slight decrease in the incidence rate when compared with Japanese living in Japan (1). Moreover, the mortality data did not reveal any significant difference from that observed in Japan (2). Such findings are in contrast with those for Japanese immigrants to the USA, who have shown a sharp decline in stomach cancer incidence, notably among second-generation Japanese Americans (3,4). This distinct pattern observed between Japanese immigrants to Brazil and the USA is in agreement with the striking differences in stomach cancer risk between the host countries, i.e. Hawaii in the USA (low-risk area) and São Paulo in Brazil (high-risk area).
Such differences suggest the importance of environmental factors in the etiology of the disease that are potentially modifiable and preventable. The gradual fall in the mortality rate in Japan following changes in food consumption to a more westernized pattern reinforces the role of environmental factors, particularly their dietary components (5,6).
The present case-control study was launched because stomach cancer poses a significant health problem in Brazil with its major etiological factors still unknown. We conducted a hospital-based case-control study among Japanese Brazilians living in São Paulo, using the same methodology as carried out among non-Japanese Brazilians (see pages 277-283).
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONAcknowledgmentsStudy Group MembersREFERENCES |
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Cases
All patients were of pure Japanese ancestry newly diagnosed with malignant neoplasm of the stomach and admitted to one of 13 collaborating hospitals for treatment in the city of São Paulo, Brazil, from June 1991 to June 1994; 101 cases were identified, five of which were excluded owing to lack of histology confirmation. With no patients refusing the interview, 96 cases (60 men and 36 women) aged 38–89 years completed the questionnaire and agreed to a blood sample collection. Among 87 cases with known location, 80 tumors (92%) were in the lower portion (body or antrum).
Controls
Two controls were designated to match each Japanese case by gender and age (within 5 years). Controls were preferably identified from among the inpatients of the same hospitals as the index cases and were interviewed within 1 month of each case assignment. In only one hospital, a specialized cancer institution, the controls were selected from neighboring public hospitals. However, it was not possible to achieve the desired matching within the hospital, and 80 of 192 control patients were recruited voluntarily from the Japanese community in São Paulo. The main reason for hospital admission of the 112 Japanese hospital control patients were infectious disease (8), metabolic disease (1), neurological disease (4), cardiovascular disease (35), respiratory disease (14), gastric ulcer (1), gastritis (2), other digestive tract and abdominal diseases (14), urogenital disease (11), dermatological disease (1), musculoskeletal disease (8), trauma (6), others (1) and unknown (6).
Interviews
Prior to the interview, a signed informed consent was obtained from cases and controls, assuring their voluntary participation in this study and the confidentiality of all information obtained. All participants submitted to an ~50 min interview by trained nurses using a structured questionnaire. One of the authors visited the interview site and monitored regularly to assure uniformity in the inquiry, especially between cases and controls. The same interviewer interviewed each case-control set. The questionnaire included detailed inquiries into socio-demographic characteristics, personal and family medical history, lifetime history of tobacco use and past dietary habits based on frequency of consumption for 30 food items. At the end of the interview, 15 ml of blood were collected for further analysis of selected biomarkers such as pepsinogen I, II levels and Helicobactor pylori antibody in sera and genetic polymorphism of metabolizing enzyme for nitrosamine (i.e. cytochrome P450 IIE1). Parts of these analyses have been published elsewhere (7–9).
Statistical analysis
Multivariate conditional logistic regression analyses were used to calculate the adjusted odds ratios (OR) and 95% confidence interval (CI) as measures of association (10). Linear trend tests for variables with more than two categories were done, assigning a continuous value to each variable category and evaluating the significance. Since healthy volunteer controls were a potential source of selection bias, the analyses were repeated after excluding them. In such a calculation, the conditional logistic analysis was based on category matching of cases and controls into 20 strata formed for each combination of gender and 10 for age group (44 or less, 45–49, 50–54, 55–59, 60–64, 65–69, 70–74, 75–79, 80–84, 85–89 years).
Tobacco consumption was calculated as pack-years, defined as the cumulative exposure equivalent to packs smoked per day times the number of years of smoking. We considered equivalence to consist of 20 commercially manufactured cigarettes (one pack), four hand-rolled black tobacco cigarettes, four cigars or five pipefuls of regular pipe tobacco (11). Lifetime alcohol consumption was calculated in terms of grams of ethanol consumed, assuming the following alcoholic concentrations: beer 5%, wine 10% and hard liquor 50%. The daily amount of ethanol (grams) was combined with frequency and year of drinking into a synthetic index. Diet was assessed with food frequency questions divided into four categories: less than once a week, 1–2 days a week, 3–4 days a week and daily.
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONAcknowledgmentsStudy Group MembersREFERENCES |
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The distribution of selected socio-economic and demographic factors in 96 cases, 192 controls and 112 controls excluding 80 volunteer controls is shown in Table 1. Significant differences were observed by country of birth, immigration history and monthly family income. The majority of controls (70.3%) were Japanese Isseis (Japan-born and first generation spent abroad) in contrast with 52.1% in the case group. However, after excluding volunteer controls, the percentage of Japan-born subjects was decreased. There were no differences in marital status or educational level. Since there were substantial percentages of unknown answers for family income and the educational level did not differ between cases and controls, only country of birth was included in the subsequent analyses for statistical adjustment.
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Table 2 shows that smoking history and alcoholic beverage consumption were not associated with the risk of stomach cancer. The associations did not change when further adjusted for beef and fruit consumption and were similar when the analysis was restricted to men. The OR for different consumption levels of selected groups of food is presented in Table 3. Among the dietary factors, daily consumption of beef was associated with a statistically significant excess risk (OR = 4.0, 95% CI = 1.9–8.4) when compared with the category of lowest consumption corresponding to those eating less than once a week after adjustment for country of birth. The OR was still statistically significant in the category of 3–4 days/week (OR = 2.1, 95% CI = 1.0–4.3). The OR increased with frequency (P for trend = 0.001) and was still statistically significant after further adjustment for fruit intake (OR = 4.4, 95% CI = 2.1–9.4 in the category of daily consumption and OR = 2.4, 95% CI = 1.1–5.0 in the category of 3–4 days/week) (data not shown in table). The elevated ORs were substantially attenuated after excluding volunteer controls; however, the OR in the category of daily consumption and the increased trend were both still statistically significant (Table 2).
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On the other side, daily consumption of fruit was associated with a reduction in risk (OR = 0.5, 95% CI = 0.3–1.0) after adjustment for country of birth (Table 2) and the risk reduction was more striking after further adjustment for beef consumption (OR = 0.4, 95% CI = 0.2–0.9) (data not shown in table). The OR reduction did not change after excluding volunteer controls (Table 2). There was no significant association between stomach cancer and the consumption of any other food items, although suggestive evidence of increased risk was observed for those who have the habit of adding salt to their food during meals (OR = 1.9, 95% CI = 0.97–4.1).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONAcknowledgmentsStudy Group MembersREFERENCES |
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This case-control study has provided an exploratory analysis of risk factors for stomach cancer in the population of Japanese immigrants and their descendants living in the city of São Paulo. The strongest risk factor in our study population was associated with a high consumption of beef and the risk increased significantly in a dose–response pattern. These observations are in agreement with previous reports from Greece (12), Italy (13) and Uruguay (14), where the consumption of beef was a risk factor for stomach cancer. However, data from Belgium have shown no such association (15). The elevation in risk ascribed to high beef intake suggests the role of fat or animal protein content. However, it may also be explained by the presence of mutagenic products released during pyrolysis of amino acids and proteins while cooking the meat at high temperature (16–18), since the typical method of cooking beef in Brazil is grilling or pan-frying.
The percentages of daily beef consumers were 51% in stomach cancer patients and only 28% in controls, but 38% after excluding volunteer controls, in this case-control study. The corresponding percentages in our previous survey of randomly selected first- and second-generation Japanese residents aged 40–69 years in the city of São Paulo were 39% (45/116) in men and 40% (52/130) in women (19). The percentage was 33% among 69 male controls aged 40–69 years in the present study, which was not unexpectedly low (Table 4). In contrast, daily beef consumed was only 2% (15/634) in randomly selected Japanese men aged 40–49 years from five areas with a threefold difference in stomach cancer mortality (20,21). The introduction of frequent beef consumption among Japanese Brazilians may be associated with an increased risk of stomach cancer in this population.
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We examined the effect of selected groups of foods by frequency of consumption and were unable to detect any significant protective effect of vegetables. Such a finding differs from those of other studies showing a negative association of vegetables with stomach cancer (13,22–24). The reasons for the divergent result obtained for vegetables may be attributed to their relatively high levels of consumption among Japanese Brazilians and the subjects’ relatively homogeneous pattern of dietary intake as an ethnic Japanese group in São Paulo, which were described in a previous cross-sectional study conducted among Japanese immigrants and their descendants living in São Paulo (19,25). This pattern of food consumption is similar to that found in the controls in the present study (Table 4).
The results of our study are in agreement with previous studies regarding such risk factors as low consumption of fruits (26,27) and heavy use of salt. Positive association with salt intake was postulated by an early case-control study in Japan (28) and has been confirmed in a number of recent studies (26,29,30). Heavy users of salt, particularly among the group who add salt to their food at table, have an increased risk (23).
Our study did not detect any association of smoking or alcohol consumption with stomach cancer. Several studies have found a positive association of cigarette smoking with stomach cancer and recent studies have supported these results (31). However, the risk increment found in the heaviest smokers is small, close to a twofold increase, and a dose–response relationship is not a common finding (22,27,29). The majority of case-control studies and larger cohort studies failed to find a positive association between alcohol and stomach cancer (5). Therefore, the evidence suggesting an etiological role of alcohol intake is weak and the dose–response relation was not reported.
Although the number of cases in our study is modest, the response rates of the eligible patients, cases and controls, were fairly high, thereby decreasing the possibility of introducing a significant bias associated with case ascertainment. We verified the dietary pattern of the general population of Japanese Brazilians, obtained by a cross-sectional study and by a survey using a self-administered three-day food record in a randomly selected population. Those findings are consistent with the pattern described for the control group in the present study (19,25).
In another paper (submitted simultaneously), we investigated the risk factors for stomach cancer among non-Japanese Brazilians in São Paulo in a case-control study, which was conducted concurrently using a similar protocol and the same questionnaire. The study confirmed most established risk factors such as low socio-economic status, cigarette smoking and low consumption of fruit and vegetables. However, cigarette smoking and vegetable consumption were not confirmed among Japanese Brazilians. The percentage of current smokers among controls of non-Japanese Brazilians was 32%, whereas it was only 17% among controls of Japanese Brazilians. Those for low vegetable consumers (<1 day/week) among non-Japanese controls were 22% for green vegetables, 21% for yellow vegetables and 9% for other vegetables, whereas those among Japanese Brazilians were 15, 4 and 6%, respectively. The low prevalence of the high-risk categories may have led to a failure to detect their adverse effects. On the other hand, beef consumption was not associated with stomach cancer in non-Japanese Brazilians.
In summary, the results of our study conducted among Japanese immigrants and their descendants in São Paulo, Brazil, support the possible role of beef intake and, to a lesser extent, the use of salt as factors increasing the risk of stomach cancer and confirmed the preventative effect of fruit intake. The null findings for cigarette smoking and vegetable consumption may be attributed to the small percentages of smokers and low vegetable consumers among them.
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Acknowledgments |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONAcknowledgmentsStudy Group MembersREFERENCES |
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This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology and for the Second Term Comprehensive 10-Year Strategy for Cancer Control and for Cancer Research from the Ministry of Health and Welfare, Japan. We thank Ms Raimunda N. Pereira, Júlia M. F. Toyota and Arlete B. Rubbo for assistance with the field work.
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Study Group Members |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONAcknowledgmentsStudy Group MembersREFERENCES |
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The investigators and participating institutions in the São Paulo–Japan Gastric Cancer Study Group were as follows: M. Asai, R. A. Possik, R. G. Bevilacqua, M. S. Oyafuso, R. S. O. Filho and D. Gastanheira (Hospital do Cancer, A.C. Camargo); B. S. Lessa, Y. Menezes, C. A. M. Fonseca and A. J. T. Nigro (Hospital Heliópolis); C. A. Malheiros and G. C. Santo (Santa Casa de Misericórdia de São Paulo); C. Kobata (Hospital São Paulo, Universidade Federal de São Paulo/EPM); A. C. de Godoi (Hospital do Servidor Público Estadual de São Paulo); J. P. A. Birindelli and L. A. Soares (Hospital Ipiranga); J. J. G. Rodrigues, K. Iriya and Y. Iriya (Hospital das Clinicas – Faculdade de Medicina da USP); V. N. Silveira and I. T. Soubhia (Hospital do Servidor Público Municipal de São Paulo); V. N. Silveira and L. T. Horita (Hospital Barro Branco); J. K. Nakauchi and M. Akamine (Hospital Nipo-Brasileiro); M. Matsuda and J. P. A. Freitas (Hospital Santa Cruz); T. Tomishige (Centro Medico ENKYO); and P. Kassab (OSEC).
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FOOTNOTES |
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+ *Study group members are listed at the end of the paper
For reprints and all correspondence: Shoichiro Tsugane, 6–5–1 Kashiwanoha, Kashiwa, Chiba 277–8566, Japan. E-mail: stsugane@east.ncc.go.jp
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REFERENCES |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONAcknowledgmentsStudy Group MembersREFERENCES |
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Received October 2, 2001; accepted April 30, 2002
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