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a I I I I I I I I I I I I I LUNG CANCER, SMOKING AND DIET AMONG SWEDISH MEN Ra ng ar Rvlander*, Gdsta Axelsson*, Lars Andersson**, Tomi Liljequist* and Bengt Bergman*** * Department of Environmental Medicine, University of Gothenburg, Gothenburg, Sweden, ** The Pulmonary Clinic, North Alvsborg General Hospital, Trollhattan, Sweden, *** Institute of Lung and Heart Diseases, Sahlgren's hospital, Gothenburg, Sweden Abstract In a prospective case-control lung cancer study in the West of Sweden, the relationship between lung cancer, smoking and dietary factors has been investigated. Suspected cases were collected from pulmonary units at two central hospitals in the area investigated and population controls of the same age and sex were selected from registers. They were interviewed by specially trained nurses, using a food frequency questionnaire. The lung cancer diagnosis (ICD 7, 162.1) was made using data from the local cancer register. In an analysis based on 308 cases and 504 controls, a dose-related increase in lung cancer risk for smokers was found although no significant risk was found for males smoking 1-10 cig/day for less than 20 years. A lower consumption of vegetables was related to a higher risk, both for smokers and nonsmokers. A higher consumption of milk was related to an increased risk. Introduction It is common knowledge that an increased risk for lung cancer has been related to several different agents in the environment such as tobacco smoke, coke oven emissions and radon. The different incidence figures for lung cancer between different countries, also among nonsmokers, suggest that environmental agents can modify the risk. On a worldwide basis, food habits show large differences between different populations. There is overwhelming epidemiological evidence that dietary factors are related to decreased or increased risks for several different forms of cancer. A reduced risk for lung cancer related to the intake of vitamin A was first suggested by Bjelke (2). Since then, about 50 studies have been published and several of these have been analyzed in two major reviews (3,4). The findings are generally that fruit and vegetables are protective factors (9,13) and a high consumption of fat (15,18) and milk (14) increases the risk. S Against this background, a major reason for the variation in lung cancer incidence in populations in various parts of the world (12,20), could be differences in diet and other life style habits, which ~ influence the risk for lung cancer (5,7). As smokers deviate from nonsmokers in many lifestyle factors (19), these could be confounders in studies on smoking and lung cancer and need to be controlled for, N to obtain accurate risk figures. ~ co v tb w 0 , 0) 00 I

A prospective study has been undertaken in the West of Sweden with the aim to investigate the risk for lung cancer in relation to different environmental factors. The origin of the study was observations of an increased risk for lung cancer among tea drinkers (6,10,16,17), but the scope was extended to incorporate dietary factors of relevance for the Swedish population. This preliminary report from the study reports the data among males and describes some dietary characteristics for smokers and nonsmokers among population controls, and the risks associated with smoking, vegetable, and milk consumption. Materials and Methods Study base, cases and controls The study base comprises persons up to and including 75 years of age of Scandinavian origin and who were registered as residing in one of 26 municipalities in Goteborg and Bogus county and Alvsborg county in the southwest of Sweden. The municipalities were selected to represent the area from which patients with suspected lung cancer were referred to the pulmonary units at the regional hospitals. Routines were established for identifying suspect lung cancer cases at three (later two) hospitals in the region. Patients referred to the outpatient department at these hospitals, and who were suspected to have lung cancer, based primarily on changes detected on lung X-rays, were invited to take part in the study. A regular control was also made of in-patients at the hospitals to ensure that lung cancer cases in the study base who had been admitted directly to the wards were included in the project. Patients willing to participate in the study were contacted for an interview. Twice a year, a search for the patients was made in the regional cancer registry. They were finally classified as lung cancer cases only if they were present in the registry. To select population controls, a list of personal identification numbers of all suspected lung cancer cases in the study base was sent to the local tax authority. For each patient, the two persons within the respective areas of the two counties, who were of the same sex as the patient and were closest to the patients in the order of the personal identification number were selected. The first person was selected unless he was an immigrant in which case the second person was selected. If a control person was a non- respondent, a substitute was not selected. A search for the population controls was also made in the cancer register. Questionnaire The questionnaire included questions on smoking, environmental tobacco smoke (ETS), occupational exposures, conditions in the residential area (local air pollution) and dietary habits. The section on diet consisted of 37 questions divided into four blocks and covered the intake of over 80 food items. The frequency questions were "seldom or never", "once or twice/month", "once or twice/week", "daily or almost daily" and for some food items "several times/day...how many?" The questions referred to eating habits during the last year. -2- I I , I I I I I I I I I I I I I I I I

i I I I I I I I I I I I I , I I I I When analyzing the data, a vegetable index was formed by amalgamating the intake of carrot, tomato, cabbage, green pepper and lettuce. The consumption of each of these vegetables was weighted as 0 for seldom/never or once/twice per month, 1 for once/twice per week and 2 for daily/almost daily consumption. The sums were divided into three classes: 0-1 (vegetable class 0), 2-4 (class 1) and 5-10 (class 2). The lowest class thus indicates that the subject consumed not more than one of the five vegetables once or twice/week. A similar index was constructed for fruits. Interviews The interviews were performed by two nurses who had been employed and specially trained for the project. In most cases the interviews were made within a few days after the suspect cases had been identified at the hospital. Thus, the interview could generally be conducted before the diagnosis was established or before the patient's condition had become so serious that an interview could not be carried out. Interviews with controls usually took place at the department or at home within 4 to 8 weeks of the patient interview. Status otthe study The recruitment of patients started in January 1989. There were breaks each summer between June and September and also a break between May 1992 and February 1993. This paper describes the analysis of all male cases and population controls interviewed between January 1989 and June 1993. Of the 344 cases, 308 (90%) were interviewed and of 644 controls, 504 (78%) were interviewed. Statistical treatment of data For estimation of odds ratios, logistic regression models were fitted to the data with the EGRET software package for unconditional maximum likelihood estimation of the regression parameters. In all analyses, there was an adjustment for age, number of cigarettes/day, number of years smoked (continuous variables), marital status (four classes) and socioeconomic job classification (seven classes). Results Figure 1 reports smoking habits among cases and controls. cases controls Never smoker .'' Former smoker - Current smoker Figure 1. Smoking history. Nonsmokers represented 5% of the cases and 32% of the controls. -3- I

I I Figure 2 reports the proportion of population controls with a low vegetable and fruit consumption (class 0) with relation to smoking habits. % of population controls 40 NS < 10 10- 19 20+ cigarettes/day Figure 2. Consumption of vegetables and fruit in relation to smotdng status. It is seen that the proportion of persons reporting a low frequency of vegetable and fruit consumption was higher among smokers, particularly among those smoking more than 20 cigarettes/day (p<0.005). For other food items, a larger proportion of persons smoking more than 20 cigarettes/day had a higher consumption of smoked/salted fish than nonsmokers (42.9 vs 26.3%, p<0.06). Coffee drinking habits are shown in Figure 3. % of population controls 75 50 25 0 NS <10 10-19 20+ , I I I I I I I I I cigarettes/day 00 ~ Consumption of coffee in relation to smoking status. Fi ure 3 ~ , W g . ~ -4- ~ ' I

I I I 1 ' I , I I I I I I I I I The proportion of high consumers of coffee was significantly larger among 20+/day smokers than among controls. For other diet items, there were no significant differences between smokers and nonsmokers, either as a group or divided into different smoking classes. Figure 4 illustrates odds ratios for lung cancer risk among smokers, as compared to nonsmokers. OR agalnst non- smoker 120 50 20- 29 30-39 40-49 years smoked Figure 4. Lung cancer risk and smoking. A dose-response was present, both regarding number of cigarettes smoked and the number of years smoked. Among these variables, the strongest dose-response was found for the number of years smoked. For those who had smoked less than 10 cigarettes a day, and less than 20 years, no significant increase in risk as compared to nonsmokers could be found. Figure 5 reports the risk ratios for lung cancer and the consumption of vegetables, in terms of vegetable classes. 0 1 vegetable class , Figure 5. Lung cancer odds ratio in relation to vegetable class. ~ i V ~ -5 W O V N k

I I It is seen that the odds ratios for lung cancer decreased with an increase in vegetable consumption. In the group with the highest consumption, the odds ratio was less than 0.5. No such relationship was found for fruit consumption (data not shown). Figure 6 shows the odds ratios for lung cancer in relation to consumption of milk. OR 4 3 I I I I I I 1- 2/month 1- 2/week daily sev times/d I Figure 6. Lung cancer odds ratio in relation to milk consumption. The figure illustrates that the odds ratio increased progressively, with an increase in milk consumption. Comments In the design of the study, we tried to minimize the influence of methodological errors by actively working for high participation rates and accurate descriptions of the personal characteristics. Regarding participation rates, several previous studies have reported between 65 and 75% and some studies even less than 50%. As it is known that risk factors are related to nonparticipation, the risk estimations in the present study are probably more accurate. The information on individual exposures was obtained in personal interviews. This secures more reliable information than that obtained through mailed questionnaires or through interviews with relatives - techniques which have been used in many previous studies. The results from this study confirm numerous previous reports that vegetables are protective against the risk for lung cancer (3,4,9). This related to nonsmokers as well as smokers. Regarding fruits, a protective effect could not be demonstrated. From a methodological point of view, this may reflect a smaller range in the consumption habits in the population studied as compared to previous studies where a protective effect has been found. On the other hand, a difference in consumption was found between nonsmokers and smokers which suggests that even the persons with a low consumption could have reached a level which gave them protection. -6- I I ' I , I 4

I I I 1 I I I I I I I I I I I I I I The data on milk consumption exemplifies the presence of natural risk factors in the diet. Similar results are reported from previous studies (14) and it has been suggested that the responsible agent is the fat in the milk (18). The dose-response for lung cancer and smoking demonstrated the expected dose-response relationship for number of cigarettes smoked and the number of years smoked. When the results were adjusted for vegetable intake, the odds ratios were almost unchanged. The number of years smoked was the most important dose determinator. The data did not demonstrate an increased risk among persons smoking less than 10 cigarettes/day and less than 20 years. The confidence levels in this group were, however, rather wide (0.25-3.38) and a larger material would be required to verify this finding. The findings in this study support a hypothesis of a balance between risk factors for a disease and protective factors. The eventual outcome of the balance between these factors determines the development of disease. The epidemiological implication of this and other studies is that investigations on lung cancer and environmental agents need to consider dietary factors as confounding agents, particularly as the consumption of risk or protective food items are different among nonsmokers and smokers. Acknowledgements This study was supported by the Swedish Cancer Foundation (contract 90-1137), the Jubilee Clinic Research Foundation, Gothenburg, Sweden, the Department of Community Medicine, Alvsborg County, Forschungsgesellschaft Rauchen and Gesundheit, MHB, Hamburg, Germany. a V 00 W O -7- ~ i

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