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Sobue*1, T., R. Suzuki*1, N. Rakayama*1, C. Inubuse*i, M. Matsudah2, O. Doi*3, T. Mori*4, K. Furuse*s, M. lukuoka*6, T. Yasumitcu*7, 0. Kuwabara*8, M. Zchigaya*9, !S. Iturata*l0, x. IN,wabara*S1, X. Nakahara*12, f. tndo*13, and S. Hattori*13. pA88IQ$ RHOXINd I11SON0 XON82SOR2N0 *OHE2i 11ND T88 RBLATZONSHIP BETREEN INDOOR AIR POLLOTIODt AIiD LVWQ CANCER INCIDENCL--REStJLTB Ot a BM+T2CENTER Ches CONTROLLED BTIIDY. Can to ]tinsho, Vol. 36, No. 3, pp.329-333. 1990. Introduction According to the 1987 population dynamics statistics oompiled by the Ministry of Health and Welfars, the age-adjustQd mortality of lung cancer in both men snd women is the second highest (after stomach cancer) among cancer mortalities". The age-adjusted mortality in stomach cancer has been steadily declining since 1960, while that of lung cancer has bean rapidly increasing during the same period. If this trend continues, the rasking of these mortalities will be reversed by the year mo~'. *1 Survey Section, Osaka Prefectural Adult Disease Center. *2 Department of Internal xedicina, Osaka Prefectural Adult Disease Center. *3 Department of Surgery, Osaka Prefectural Adult Disease Center. *4 Department of Surgery, National Sanatorium xinki Central Hospital. *5 Department of Internal Medicine, Kational Sanatorium Kinki Central Hospital. *6 Department of Internal Medicine, Osaka Prefectural Habikino Hospital. *7 Department of Surgery, Osaka Prefectural Habikino Hospital. *s Department of Snternal Medicine, National Sanatorium Tonsyama Hospital. •9 Departmant of Respiratory Diseases, Osaka Red Cross Hospital e10 Department of Thoracic SurQsry, icitano Hospital. *11 Department of Respiratory Diseases, Kansai Denryoku Hospital. *12 The First Department of Surgery, Osaka LJniwersity School of Medicine. *13 The organization to Eliminats Lung Cancer from Osaka.

For risk factors to explain this rising ineider.ce of lung cancer, smoking is cited first. Zn Sapan, the incidence of smoking among men has been declining in recent years but it wa.s reported to be 55% in 198s31, a rat. considerably higher in cotnparison to the incidences in the western worid. Thus the promotion of an antismoking policy is considered to be necrssary. hlthough the incidence of smoking has reeently been increasing among young women, it was reported to be mere a l%s~ in 1969, a figure much Sowor than those in western societies. To xeflect this situation, the population-attributable risk of lung cancer due to smoking is 71t in meri and only 26% in vomen;). In other words, it is suggested that risk factors other than smoking exist in the development of lung cancer among women. Yn the past, for risk factors other than smoking that cause lung cancer to develop, studies have been conducted with a major focus on occupational exposure. =n women, however, it is necessary that studies on exposure to various elements in the everyday environment supersede the investigation of the effects of occupational factors. liovever the relative risk of these elements in everyday environment is expected to be comparatively small. Thus it is necessary to include as many cases of lung cancer among nonsmoking women as possible for the analysis. The purpose of the present study is to elucidate the risk factors of lung cancer among nonsmoking women. Theretore the status of passive smoking and the relationship between indoor air pollution and the development of lung cancer were investigated, using the data irom the case-aontrolled studies conducted jointly by a number of health facilities. It should be noted that the study uses data collected up to the end of March 19391 thus the ligures may be different in the final section of the report which is scheduled for the coming year. 1. =ubjects and Method. The "organixation to Eliminate Lung Cancer from osaka"1}P with the participation of s major hospitals in Osaka specializing Sn the treatment of lung cancer, has been conducting a hospital- based case-controlled study since January 1936. Among the 2

patients newly admitted with a diagnosis of primary lung cancer, 658 men and 193 women were reqistered by the end of March 2989. only 33 out of these 638 men (3.58) were lifetime nor.smokers. Among the 193 female patients, however, 120 (62%) were nonsmokers. The present analysis was limited to these nonsmoking lamale patients. Of the lung cancers in these nonsmoking women, 78% were elassified as adanocarcinoma. For control, $19 nonsmokinq female patients were selected from those newly admitted to the same hospitals with a diagnosis other than lung cancer. Neoplastic diseases were th. predominant diagnosis (8s=) of these patients. Breast cancer (240 cases) was the most common, followed by stomach cancer (63 cases). For the ana2ysis, the ages criteria at the time of admission was set from 40 to 79 years for both the lung cancer patients and control. The information on smoking and indoor air pollution was obtained from a questionnaire, filled out by the patients, which was distributed and collected at the time ot admission. Any questionable responses concerning the present analysis were excluded from tabulation. Medical information such as histological type of cancer was obtaired from attending physicians. The age•adjudted odds ratio and 95% conf idence level were computed by the Mantel•Haenszel metbod using the PROC FREQ of SAS0. Factors with an estimated value of the odds ratio over 1.5 or below 0«t7 were selected and subjected to a logistic regression analysis using PROC LOGiST of SAS". 2. Results Table I shows an aQe-adjustsd odds ratio where the population was divided into those with smoking husbands and other members of the family who were smokers. TAa table was prepared to find the effects of passive smoking on lung cancer in adults (prior to hospital admission). The odds ratio when the husbands wers smokers was almost 1(0.94), while smoking by other members in the household raised it to 1.45, indicating a slight increase in risk. Most of the other smoking members in a household were ~ children. To find the effects of passive smoking during early C!1 C~7 3

Childhood, tl`le age-a4justed odds ratios were computed when fathers, mothers, or other members of the household were smokers. Thp results are shown in Table 2. When fathers were smokers, the odds ratio of passive smoking was 0.60, with a significant reduction in risk. When aothars were smokers, the odds ratio was computed to be 1.71. The risk rose in this instame but the Change was not significant. The odds ratio for smoking by other members of the families was computed to be 1.13. Table 3 shows thQ effects of using room beaters (which may be a cause of indoor air pollution) on the development of lung cancer as an age-adjusted odds ratio. The ratio was computed separately for each age category when the beater was in use. For heating facilities which may be the cause of indoor air pollution the following were included: unvented stoves using gasoline, gas, ooal, charcoal briquettes, or woodr or a brazier, clay charcoal stove, or loot warmer which burns charcoal or briquettes. Air conditioners, stoves with vents, electric stoves, and electric toot warmers were exciudadfrom the study. Odds ratios were computed in relation to the use of these sources of pollution at each ago level when the heaters were used. As shown in Table 3, the ratios were near 1 for each age level, showing no significant relationship. The effects of using foot warmers (burning charcoal, small briquettes, or round briquettes for the source of heat when sleeping) on the inaidence of lung cancer were studied and expressed as an age-adjustQd odds ratio in Table 4. These ratios, shown by age level, ware near I for all ages, indicating no significant relationship. NeXt, age-adjusted odds ratios were computed for the effects of using straw or wood for cooking on the developzent of lung cancer (Table S). Again, the ratios were computed for each group. The ratio was 3.33 when the fuel was used at ag. 15 and 1.90 when used at age 30, with the latter showing a statistical significance. A11 the patients who had been using straw or wood for cooking at age 30 had also used the same fuel at age 15. Therefore the odds ratio computed at age 30 was intQrpret.d to 4

express the effect of long-term exposure to this source of pollution. None of the patients was still using straw or wood as a source of cooking heat. In these analyses, the oddg ratios for the following 3 situations ware computed to be over 1.5 or less than 0.67: smoking by father or mother when the patient was young and the use of straw or wood as the source of cooking heat at age 30. Vsinq these 3 situations as variables, the odds ratio was estimated using a logistic regression model (Table 6). It was found that only the use of straw or wood as the source of cooking heat at age 30 showed a statistical significance. 3. Discussion The results of the present study suggested that the use of straw or wood as a cooking fuel in the past is a risk factor in the development of lung cancer among nonsmoking women. Gao, et al.la investigated women in Shanghai and reported that the use of rapeseed oil raises the risk of lurg cancer by 40%. In the same report, the use of cooking fuel (coal, city gas, and wood) did not increase the risk. Koo, at al.8) conducted a study on women residing in Hong Rori4 and reported that among cooking fuels, the use of petroiewz increases the risk of lung cancer while the risk is lower when propane gas (LPG) is used. However they added that these effects are relatively insignificant. MacLennan, et al.1D1 conducted a study on Chinese women in Singapore and reported that there was no difference with respect to the risk of lung cancer when wood or charcoal used as cooking fuel was compared against petroleum and gas. The subjects of these studies wers all Chinese women. xn addition, exposure was based on whether the sub~ects ever used the fuel in question at all in the past or whether they are currently using it. suc2a criteria aay not necessarily reflect past exposure accurately. furthermore there is a possibility that those vho were classified as Rnot exposed" may actually have been substantially exposed. If these possibilities are taken into oonsideration, the results of these studies do not necessarily contradict ours. No subjects currently use straw or wood for cooking fuel so 5

we could not institute a policy of primary prevention of lung cancer in relation to this practice. However the finding is considered significant in suggesting that sQme factor(s) closely related to our daily lives may be recognized as risk factor(s) for lung cancer that appears 10 or 20 years later. No statistical significance was obtained from the effect of maternal smoking when the subjects war• young.PCoVlver the ~ atimated odds ratio was high ti.?9) and the power to detect the`' - .~... .. .: ,. :,, :w,_. . -.,,; :. .: ... < -...;.. . ,. siqnificant dl.ffar.nee tro~a th~ aases ot tha p:eseat study yas ' computsd to be 56% , &'There=or• further studies with a larger number of subjects are considered necessary. As for the short- term effect of maternal smoking on the health of children, Tager, at al.11i reported that the respiratory function was depressed in children when parents were smokers and the tendency was exaggerated when the mothers were smokers. Wu, et 0.12) conducted a case-controlled study on white wonen in Los Angeles but they lailed to find a significant relationship between lung cancer and maternal smoking. Sn Japan, Shimizu, at al.'a~ reported an odds ratio of 1.6 for maternal smoking in relation to lung cancer in women. In the present study, the risk of lung cancer from paternal smoking was significantly reduced in a single variate analysis but the results of a multivariate analysis wera not significant. Compared with the mother, the time a child spends with her father is expected to be shortt and the tendency towards a decline in risk is believed to be due to some confounding factor (such as social class). For the effect of passive smoking during adulthood, the present study focused on smoking by husbands but no significant correlation with lung cancer was established. In Japan, HirayamalQ, and Akiha, at a1") ' found a significnat relationship between the two but Shimizu, et ai.t3'' did not. Slot, et a1.16) conducted a meta analysis based on eqidemiologieaT data throughout the world and estimated that husbands' smoking raises wives' risk for lung cancer by 904. The 954 confidence range of the odds ratio in the present study is 0.62 to 1.40 and includes 6

1.30 within but a clearcut conclusion could not be drawn from such an uncertain risk factor. The present study a2so indicated that the effect of smoking by other members of the household, rather than by husbands, -tends to be saore significant. Shimizu, at al.u~ reported that smoking by fathers-in-law who lived in the same householdg has a more significant effect than that by hursbands. The analysis in the present study failed to show an increase in the risk of lung cancer in relation to the use of heating equipsaent. For the use of various heating devices, LeungtT) reported that the use of petroleum stoves raised the risk of lung cancer among women in 8ong Xonq. In aapan, however, shimizu1a) conducted a case-controlled study in Nagoya in whiehno 3ncrease in the risk of lung cancer was recognized in association with the use of petroleum stoves. The most serious problem inherent in the r.thodoloqy of the present study is a large number of cancer patients (especially those with breast cancer) included in the control. Both the cases and control xexa nonsmokers and there have been no reports on the relationship between the exposure factor--the subject of the present analysis--and cancer involving other organs. Therefore inclusion of a large number of cancer patients is not considered to present a serious problem. However dominznce by a single clinical entity (breast cancer in this instance) is not desirable in view of the nature of the control. The authors plan further studies using a larger number or patients and an improved analysis of the control. The authors express their gratitude to Dr. Banai (Osaka Adult Disease Center) who prepared the original form of the questionnaire for the present survey under the guidance of Dr. Muir (Z1RC). 7 z

Table i. Odds Ratio of Passive Smoking in Adulthood (beZora Nospitalitation) Lun"ancerfControl Odls Rati4 (95% Confidence Level) Smoking by Husband no 56/229 1.00 yes 64/200 0.94 (0.6Z-1.40) Smoking by Other Members no 77/384 1.00 yes 43/iss 1/43(0.9a-2.23) *Adjuated by age at hospital admission. Table 2. odds Ratio of Passive Smoking during Childhood I:uneL,Ca_ncQ_r/Cflntrol Qdd9 Ratio' (9s4 Confidence Leval) Smoking by Father no 47/1<4 1.00 yes 73/375 0.60(0.40-0.91) Smoking by Mother no 102/473 1.00 yes 18/46 1.71(0.95-3.10) Smoking by Other Members no 9S/416 1.00 yes 25/103 1.13(0.69-1.87) *?,djusted by age at hospital admission. •

Table 3. 0dds Rntio When Heating L'quipment Which May 8e The Cause of Yndcor Air Pollution is Qsed--Observation in Relation to the Age When the Equipment Was IIsed Vse ef EauiAlnent Lunc Car erLCQntral Odds atio (954 Confidence heve l ) At Age 35 Aot used 37/150 1.00 used a3/369 0.94(0.60-1.45) At hge 3 0 not used 45/212 1.00 used 75/307 1.09(0.72-1.6s) At Presezt 1iot used 65/289 1.00 used 55/230 2.07(0.71-1.60) • Adjusted by age at admission. Table 4. odds Ratio When Toot Warmers Wete Vsed During Sleep--Gbservaticn at Each Age Level us* ot the -E_,gyj ment Lyria Carcerlgontrol Odde Ratia (95% Confidence Level) At Age is not used 76/]27 1.00 used 44/l92 0.97(0.64-1.47) At Age 30 not used 95/429 1. 00 used 25/90 0.69(0.S3-1.51) At Present not used 119/514 1.00 used 1/5 0.67(0.09-4.99) • Adjusted by age at hospital admission. 9

fiabla 5. Odds Ratio Whes, Straw and wood Are Used for CooXing Fuel jZSe of _thl Lung_CancerjCortr2l bddlRatio At Age is (95% Confidence Level) not used 46/2S2 1.00 used 74/267 1.33(0.87-2.02) At Ags 30 not used 94/469 1.00 used 26/ so 1.90(1.09-3.30) At Prt sent not used 123/519 used, 0/0 * Adjusted by age at hospital admission. Tab2s 6. Age-Adjustsd Odds Ratios for Maternal and Patarnal 6moking during Childhood; and t2ie Use or Straw and Wood as a Cooking Fuel at Age 30, Calculated by Logistia Regression Analysis gactere Odds Ratios (9S4 Confidence Lsval) Matsrnal bmoking During ChiTdbood 1.8Z(0.98 - 3.37)' Paternal Smokircg During Childhood 0.70(0.43 - 1.16) iJse of Straw and Wood as cooking Fuel at Age 30 I.7i(1.02 - 3.10) cc 7V to ~EA 0)