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AN EPIDEMIOLOGICAL ANALYSIS OF SOME RISK FACTORS OF LUNG CANCER -- INDOOR AND OUTDOOR AIR POLLUTION Du Ying-Xiu, Huang Lan-fang, Chen Xiao-wei, Feng J.W. Introduction In China, lung cancer mortality rate is the highest among all cancers. The average mortality rate for 16 cities was 565/100,000 from 1982 to 1988, with no appreciable change during the seven-year period. (b = 0.001, P > 0.05) However, the mortality rate for all cancers has been on the rise: 100/100,000 in 1982, 125/100,000 in 1986 (b = 0.0117, P> 0.05), in which lung cancer not only accounted for 25% of the total deaths, but its death rate is on the rapid rise, 25/100,000 in 1982, 32/100,000 in 1988 (b = 0.0151, P > 0.01). In 1989, lung cancer death rates in Guangzhou became the third highest in China, lower only than in Chongqing and Shanghai; it was one of Guangzhou's five leading cancer-related death rates according to international standardized mortality•rate (number of deaths per 100,000): lung cancer 39.79/100,000, liver cancer 24.12/100,000, stomach cancer 9.67/100,000, nasopharyngeal cancer 6.07/100,000 and esophageal cancer 5.00/100,000. Notably, lung cancer death rate is the combined total of liver cancer, stomach cancer and nasopharyngeal cancer death rates.

Air pollution, smoke and certain occupational exposures have been recognized as the three most important risk factors in lung cancer. However, their significance may vary according to locale or sex. In order to examine the potential risk factors of lung cancer in Guangzhou, we have undertaken an analysis of relevant data collected in the last 20 years. This paper discusses, primarily, lung cancer's relationship with indoor/outdoor pollution. The association of atmospheric air pollution and lung cancer has long been noted. In 1959, P. Stocks reportedl that lung cancer incidence in various areas of Great Britain was related to local atmospheric deposit index, smoke index, and population density. He further emphasized the close relationship between lung cancer and 3, 4 benzopyrene, beryllium, molybdemun, vanadium and arsenic2. In 1976 W.J. Blot3 in analyzing the higher distribution of lung cancer deaths in the U.S. in locations of paper manufacturing, chemical engineering, petroleum, and vehicle manufacturing plants found that lung cancer is associated with atmospheric pollution and occupational exposures. Z.Y. Xu and W.J. Blot4 in their 1989 case-control study of the industrial city of Shenyang, found that, other than smoking, lung cancer was related to indoor/outdoor pollution. Higher rates of lung cancer occurred in men and women living near refining facilities for a greater number of years. In indoor air pollution, coal-burning "kangs" - 2 -

appeared to be an important contributing factor. They believe smoking and indoor/outdoor pollution were associated with squamous cell carcinoma and small cell carcinoma. In his 1987 case-control study in Shanghai5, Y.T. Gao found that indoor air pollution and use of rapeseed oil for cooking had important cooking significance in female lung cancer. However, it must be noted that the relationship between air pollution and lung cancer is a complex one. This is because on the one hand lung cancer is known to be related to multiple risk factors and long latency, air pollution, especially atmospheric pollution, on the other hand, is subject to constant changes. Thus, in order to accurately assess the relationship between the two, one must not only exclude confounding risk factors but must also rely on data generated by long-term observations. This is realistically difficult to accomplish. To examine the relationship between indoor/outdoor air pollution and lung cancer, we have combined the atmospheric pollution data of the last 20 years in the southern Chinese city of Guangzhou, some 2-year indoor air pollution data and Guangzhou's lung cancer mortality rate of last 10 years in a retrospective case-control study. Materials and Methods - 3 -

1. Retrospective study of lung cancer deaths. The population of Guangzhou is approximately 2 million residing in 4 geographic districts, served by 63 local police stations. Each local police station keeps complete and systematic records of the residents, which include population characteristics such as number of residents, sex, age, occupation, street address, annual registration of births and deaths, (including time and cause of death), etc. In 1980 we concluded a retrospective survey of every lung cancer death by interviewing relatives of the decedent using standardized questionnaires. Questionnaires were filled by trained medical staff. The surveys also were conducted once very year to cover lung cancer deaths occurred in the previous year; the surveys combined information from hospital case histories prior to death. All data were input into computers to establish a database. Data fields include: Name, sex, father's place of birth, date of birth, date of death, native city, proximity to sources of pollution, education, marital st r atus, religion, date of initial lung cancer diagnosis, where diagnosed, level of diagnosis, method of diagnosis, cell type, tumor location, involvement of lung, metastases, site of metastases, medical history, smoking history, smokers in household, family status, kitchen facilities, diet - 4 -

! history, occupational history, family tumor history, respondent, hospital record, respondent's cooperation. 2. Atmospheric pollution. The geographic area of Guangzhou is about 55 square kilometers, divided into Liwan, Yuexiu, Dongshan and Haizhu four districts. From 1972-1977 the Guangzhou Health and Anti-epidemic Station established 30 atmospheric pollution observation stations and tested the atmospheric content of SOz and sedimentated dust (S[)). SO2 (µg/M3) was analyzed using (?) method from seasonal samples of 5 consecutive days, taken once every month, three samples a day. The samples were collected in glass containers of 15 cm diameter and 30 cm height, placed on roof-tops. The naturally sedimentated dust was measured by weight in ton/km2/month. During 1981-1990, according to WHO Global Testing Plan, four testing stations were established in Liwan, Yuexiu, Dongshan, Haighu and a reference station, to study the total suspended particulates, (TSP) of 502. SO2 and TSP, continuously collected from the first to the fifteenth day of each month, were analyzed according to WHO criteria.6 - 5 -

The databases established from the two above testings were quite large. To assess atmospheric pollution, the air pollution index of Guangzhou was calculated by using the following formula. 1 n Ci API = E n i=1 Si n - air pollutants tested c - concentration of air pollutants s - permissible level of pollutants In December of 1984, the Guangzhou Municipal Science & Technology Committee organized an aero remote sensing test for the city of Guangzhou. Atmospheric pollution was assessed by observing the effect of pollution on plants by the vegetation ecoline on air infrared color film and sychromonitoring. Levels of air pollution were classified as clean, light, medium, heavy and severe. 3. Testing of indoor air pollution. In order to examine indoor air pollution caused by coal fume, a two-year continuous systematic study of indoor air pollution was conducted. Five households from each of the four districts of Guangzhou, 20 in total were randomly selected. The daily and seasonal variations of SOz and NOx were tested 7 times daily with samples taken every two hours from 7 a.m. to 7 p.m. in - 6 -

5 consecutive days, once during each season, i.e. four times in a year. Since the 1980s citizens of Guangzhou have been in the process of switching over from coal to gas. In order to compare the indoor air pollution caused by each fuel, 5 coal user households and 5 gas user households were again selected from the four districts in 1986. The indoor air contents of SOZ, NOx, CO, TSP, SD, B(a)P, radon and thoron were tested. Moreover, the urine B(a)P level of housewives in both coal and gas households was tested. The housewives were all non-smokers with at least one year's experience in managing the households. SO2 was analyzed by (?) method, NOx by (?) method, CO by (?) method, TSP by (?). SD was weighed after 15 days after exposure of 15 days in shallow dishes of 15 cm diameter and placed 1.7 meters above ground. B(a)P by (?), urine B(a)P content by (?). Radon and thoron samples were taken by DK-60 samplers, and examined by FJ-13 a radiation instrument. 4. Case-control study. In 1985 there were a total of 806 cancer deaths (531 ma].es, 275 females) in Guangzhou. We matched the lung cancer death cases with controls of non-cancer deaths in the same residential - 7 -

area with death occurring in the same year, matched for sex, age (± 2 years), and obtained 659 pairs (82% of total number of cases), consisted of 143 male pairs and 216 female pairs. By using Mantel- Haenszel method, we calculated the relative risks of smoking and exposure to coal dust at 95% confidence level. Results 1. Regional distribution of lung cancer deaths. Between 1980 and 1988, a total of 6,812 lung cancer death cases (4,615 male, 2,197 female; ratio 2.1:1) were registered at in the 63 local police stations in Guangzhou. Based on this information the regional distribution of lung cancer deaths was calculated and shown in Figure 1. The highest lung cancer rate (37.94/100,000) was found in Liwan, and in descending order, Yuexiu (35.99/100,000), Haizhu (31.50/100,000), and Dongshan (30.79/100,000) (Table 1), suggesting a history of pronounced difference in lung cancer death rates by districts in Guangzhou. 2. Atmospheric pollution. Between 1972 and 1979, data obtained at 30 sampling a stations were used to calculate the atmospheric pollution index (API) . It was found that Liwan has the highest API (2.49), and is - 8 -

followed by Yuexiu (1.68), Haizhu (1.64) and Dongshan (1.17). For comparison, the "control" region only had an API of 0.57. Between 1982 and 1990, four sampling stations were established in order to provide 24-hour around the clock monitoring. Samples were obtained on 180 days each of the 9 years and then analyzed. The results show that Liwan had the most severe API (0.898), and was followed by Yuexiu (0.721), and lastly Dougshan (0.470). For comparison, the control district only show a pollution index of 0.246. The severity of atmospheric pollution was also studied in 1984 with an aircraft base monitoring system which further substantiated Liwan to be a heavily polluted district. According to the same survey,Yuexiu was only moderately polluted; Dongshan and Haizhu/ was lightly polluted, and control was considered to be clean. (Table 1) Results of these surveys are displayed in Figures 2-4 which show clearly that atmospheric pollution is mostly concentrated in the Liwan district for the past 20 years which is ; highly correlated with the highest rate of lung cancer deaths. 3. Indoor air pollution. Indoor and outdoor air pollution studies carried out over a two year period show that indoor air pollution was more sever - 9 -

than outdoor pollution (Table 2). This probably reflected the fact that at this period of time most of the factories in Guangzhou were located outside of the city and cars were rather scarce between 1984 to 1985. Three peaks;of indoor SOZ and NOX were found. (7 a.m., 11 a.m. and 7 p.m.) which were also substantially higher in winter/spring months when doors/windows were generally closed, than in summer (Figure 4), suggesting that the primary source of indoor air pollution came from cooking. Residents of Guangzhou depended on wood in the 'SOs, on coal during the '60s, and progressively switching to propane and gas in the '80s. In 1991 about 40% of the families in Guangzhou used gas. Thus, indoor air pollution was probably most pronounced between 1960 to 1990. Table 3 compares the indoor air pollutant levels in houses using gas as compared with those using coal. Not only is indoor air pollution higher in coal users, housewives and families using coal also had higher concentration of benzo(a)pyrene in their urine. 4. Case-control study.