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SOME LIFE-STYLE FACTORS IN HUMAN LUNG CANCERs A CASE-CONTROL STUDY OF 792 LUNG CANCER CASES Lei Yi-Xiong, Chen, Y. Z., Du Ying-xiu The lung cancer death rate has become one of the highest among malignant tumor related deaths in urban populations in many parts of the world. Although there has been some understanding of its etiology, many observations relating to lung cancer cannot be explained adequately by our current understanding. For example, the smoking rate is not necessarily lower for peasants than for the city dwellers; however, peasants have a lower lung cancer rate than city dwellers. Conversely, although the smoking rate for women is far lower than for men, the lung cancer incidence is higher than for men, indicating the existence of risk factors other than smoking. The lung cancer mortality rate has been rapidly increasing since the 1970s in the city of Guangzhou. For instance, the standardized mortality rate (SMR) for lung cancer increased from 25.6/100,000 (31.9 in males and 18.8 in females) in 1976 to 40.3/100,000 (55.8 in males and 23.9 in females) in 1986, representing an average annual increase of 1.57/100,000 over the 10-year period. in order to investigate a relationship between some lifestyle factors and lung cancer, a case-control study involving all lung cancer deaths registered in 1986 was performed. Items surveyed and analyzed included: active smoking, exposure to

ETS, diet, living conditions, kitchen facilities, and exposure to coal smoke fume and dust. Materials and Methods 1. Study population. All primary lung cancer deaths in Guangzhou were investigated retrospectively in case-control study. Lung cancer deaths in all four districts in Guangzhou during 1986 were collected from permanent resident records, routinely maintained by local police stations. Deaths unrelated to primary lung cancer, or of those below 10-year residency were excluded. Controls were selected from the same year of death, residence on the same street as controls had no history of respiratory diseases or tumor related diseases, and matched for sex, age (± 5 years) . The purpose of the method of this selection method was to exclude latent cases. The criterion of same-street residency was to exclude the potential difference in the effects of indoor and outdoor air pollution. In 1986 there were 831 lung cancer deaths in Guangzhou, 792 of which were matched with controls, 95.3% match from the total), 563 male pairs and 229 female pairs. 2. Method of investigation. - 2 -

Home interviews with relatives of the decedents were conducted. Information was supplied by spouses or co-habitating relatives. The content, order and style of the questionnaire used for• both cases and controls were standardized in terms of content, order and style, the interviews were conducted trained information takers. Data were taken the same investigator in pairs of cases and controls, including the hospital case histories of both groups. 3. Survey contents. In addition to routine information relating to characteristics of both cases and controls, population based studies, data were obtained on the following five specific areas: (A) Smoking history: specifically, daily smoking rate (cigarette/day) , age at which began to smoke, number of years smoked and smoking index (daily smoking rate x number of years smoked). The smoking index was divided into four categories: 0, < 400, 400-, 800-. For analytical purposes, the smoking index was used as the primary quantitative measure of the effect of the smoking history. (B) Exposure to ETS. In order to assess the effects of exposure to ETS, the effect of active smoking must first be excluded. Because in the case of male lung cancer death cases, 92% of the cases were active smokers and because the effect of exposure to ETS in workplace cannot be accurately determined, the present survey dealt primary with the effects of exposure to - 3 -

spousal smoking in non-smoking females. Daily cigarette smoking rate and the number of years smoked by husbands were used in the statistical analysis. (C) Diets and eating habits: These included consumption of pork, beef, poultry, fish, eggs, milk and dairy products, leafy and non-leafy vegetables, fruits, fried food, pickled vegetables, salted fish and smoked products. The consumption of these food items was stratified into the categories of: never, weekly, and daily. (D) Living conditions. Information concerning the following were obtained: old or new building; location of residence within the building, (ground level, , second, third, or fourth floor and above); internal dimensions, which included ceiling height (6, 9 or 12 feet) and average size of living area per person (18, 36, 54, 64 square feet per person) ; ventilation (excellent, average, poor) ; and use of insect repellant incense (never, occasional, average, and frequent). (E) Kitchen facilities and exposure to coal fume and dust. Information obtained included, average kitchen size (less than 9, 9, 18 square feet or above); and cooking fuel (coal, propane, wood). Information was also obtained regarding exposure to benzo(a)pyrene as pollutants generated by frying food, and cooking practices, e.g. preference for fried food. 4. Methods of analysis. - 4 -

(A) Qualitative data analysis. To estimate the accuracy of the information collected, 1% of the total samples were randomly resurveyed. Consistency of data between the first and second surveys were evaluated by the Kappa test using the following equation. I{ = Po - Pe 1 - Pe In which Po = consistency of observation, Pe = the value expected based on consistency of chance. The significance of the Kappa test was assessed by the value of fleiss as follows, 0.75:1.00 excellent consistency; 0.4:0.75 average consistency; 0.01:0.3 lacking consistency. (B) Compatibility of information obtained on cases and controls. Information evaluated in the compatibility test included: Father's place of birth: Guangzhou and outside of Guangzhou. Marital status: single, married, divorced, widowed, separated. 5

Education: illiterate, primary school education, middle school education, high school education, technical school education, college education. occupation: specialist, government official, clerk, businessman, service personnel, manual laborer, and others. The X2 test was used to determine the average reliability of data. (C) Analysis of factors investigated. The X2 value was calculated by the McNemar's method. The odds ratio with a 95,% CI was determined according to Miettinen. To obtain information on total exposure, the cumulative X2 was calculated by the RxC method. Results and Analysis 1. Measurement of data. Data from 272 samples, i.e. 8 pairs of cases and controls and 17 risk factors were taken by investigators A and B. The results show the data to be authentic and reliable. - 6 -

Table 1 272 Samples of Risk Factors Taken By Investigators A & B Investigator B Investigator A Tota]. Yes Yes 99 15 114 No 10 148 158 Total 109 163 272 Result of Kappa Test: K = 0.81, 2. Test of equilibrium. P < 0.001 Uniformity exists for cases and controls in sex, age of death, and street address. Other characteristics of cases and controls include father's place of birth, marital status, education, and occupation which also exhibited uniformity. No difference was found by the test of equilibrium, which demonstrates good comparability between the two groups. Table 2 Demographic Characteristics of Cases and Controls Nale Cases Conthols remate Cases Controls 7

Father's place of birth Guangzhou Province 465 454 179 182 Province other than Guangzhou 32 43 12 9 X2 = 1.745 P> 0.05 X2 = 0.213 P> 0.05 Marital status Single 13 22 8 6 Married 476 473 147 139 Divorced 14 8 1 4 Widowed 28 34 64 67 Separated 12 6 3 7 X2 = 6.541 P> 0.05 X2 = 2.158 P > 0.05 Education Illiterate 47 44 100 107 Grade School 264 249 80 69 Junior High 131 124 23 26 High School & Technical 66 81 15 16 College 36 46 4 4 X2 • 3.400 P> 0.05 X2 • 1.258 P > 0.05 Occupation Highly skilled 49 50 19 9 Government official 46 48 2 2 Clerical 32 46 4 4 Other 35 49 38 46 Business 41 56 12 13 Service personnel 48 40 21 19 Laborer 270 232 75 78 X2 = 10.822 P> 0.05 X2 = 4.532 P> 0.05 3. Analysis of smoking history. Among the 563 pairs of cases and controls, the smoking percentage of smokers was 92.5% for the cases and 75.5% for the controls. Among the 229 female pairs, the smoking rate was 60.6% for the cases and 30.8% for the controls. The majority of smokers smoked cigarettes (68.2%), the next largest smoker group used roll- your-own cigarettes (28.3%), used a few water pipes (1.9%), and a very small number used pipes and cigars. Though there were no apparent difference between cases and controls in the type of tobacco products used, in the smoking index, there were not only significant difference in both male and female cases, but the test - 8 -

of trend showed an obvious dose-response relationship. (Table 3) The results show that smoking is an important risk factor in the incidence of lung cancer among residents of Guangzhou. Table 3 Distribution of Smoking Index in Cases and Controls Smoking index.; Cases Controls 0R 95% Confidence Cevel Tests H: 0 41 123 1.00 1.00-1.00 Tlst of hypothesis < 400 57 93 1.84 1.24-3.26 X= 77.71, P < 0.001 400- 136 122 3.34 2.72-5.60 Tgst of Trend 400- 250 146 5.36 3.60-7.93 X= 77.33, P < 0.001 F: 0 85 147 1.00 1.00-1.00 Tgst of hypothesis < 400 29 26 1.93 1.70-3.02 X= 44.68, P < 0.001 400- 33 16 3.57 2.45-5.11 T2st of Trend 800- 61 19 5.55 3.21-7.22 X= 43.92, P< 0.001 Note: Smoking index - daily smoking rate x total years of smoking. 4. Environmental Tobacco Smoke Exposure. To determine the effects of husbands' smoking on their wives, whether the spouse was a smoker, daily smoking rate, and years of smoking were examined as the bases of exposure 'to environmental tobacco smoke (ETS). Results of effects of husbands' smoking on non-smoking wives on cases and controls were compared in Table 4. Table 4 - 9 -

Distribution of ETS Exposure Among Non-Smoking Cases and Controls Cases; Controls. OR ;, 95% Confidence level- ETS exposure No 28 53 Yes ~7 75 1.19 0.66-2.16 X = 0.327 P > 0.05 Amount of ETS exposure 0 28 53 1.00 1.00-1.00 (number of cigarettes) < 20 13 34 0.72 0.53-0.98 20- p 35 1.62 1.03-2.55 X = 4.308 P > 0.05 Years of exposure to ETS 0 28 53 1.00 1.00-1.00 (years) < 30 14 19 1.39 0.63-1.60 30- ~9 47 1.17 0.80-1.25 X = 0.652 P > 0.05 5. Diet. Food categories analyzed include: pork, beef, poultry, fish, egg and dairy products, leafy and non-leafy vegetables, fruits, fried food, preserved vegetables, salt-preserved fish and smoked and cured products. The results show fresh vegetables and fruits to have protective properties against male lung cancer. On the other hand, fried food may contribute to the risks of male lung cancer. No differences were shown for the remainder of the food categories. (Table 5) When data were stratified into never or frequent (almost daily) intake groups for comparison, then the relationship of frequent intake of vegetables and fruit and the decrease in the lung cancer rate became more obvious. (Tables 6, 7) Table 5 - 10 -