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Lung Cancer: Causes and PreveMion PrxWlnQt of fhe lrtt.mvtlond LurV CcncOr Updvft ConhMcO, hNd !n Iil.w Or*oreA Loulslcna, Morch 3,5, 1963 Edled by M.ft Mtz.11 and Po1cyo Cocr+m ~ ~ i1!¢T~atiOnal Ci W GO N FA CD N

Contenta Keynote Addras: The Control of Lamg Cincer Richard Petc and Richard D*U I Chaprff 2 Lung Cancer in Scandinavia: Time Tpends and Smoking Habits 21 Laly Teppo Gaapter 3 Trends in IIamg Cancer Inodence and MoralitF in the United Satd 33 Snnm S DrveyoQ john W. Horn, and Roger R Connelly ChapUr 4 Lung Cancer and Occupationil Pacposures 47 Wi11im j. BJot Chaptef 3 Air PoRudon and Lung Cancer 65 C'arf M Shy Chapcer 6 The Causes of Lung Cancer in Loaisiznz 73 Pelayo Corrr.a, I~da Ar'ctZimW Acw IIi:abeth FonMmx, Nancy Dolceges, Youpvr$ 1,in, WOam H'a!,-.rsl, and tii'iMmie D. johnson Chapw 7 The Causes of Limig Cancer in Tac~ 83 Patr;do .iL Bufflkr, F.inda WOm,a Pick1S Tfwmar j. Moswy and f.7wrla Contost C'J+cpter 8 Recent C'sse - ControZ Studies of Lm: Cancer in the United States 101 Linda fPd7imps PicATR Pelayo Corrio, and Flizabeth ForitJiaw Chaptcr 9 The Epidemiologic Meaning of Frstorogr in Lung Csnces 117 john WBerg ~

f3icQten 10 Lung Cancer in Noasmokrrs and Low-Risk Populations 131 Chapter 11 Jaeph L Lyon, FLecera D. Aaloa, and John W. Gardner Ecogenetico of Lung ('ancer: Genetic Stsscepabi'litT in the Etiology of Lung C.ancer 41 Chapter 12 Jo1w J. Mukfi)eiII and Allen E Bale Trends in hi'istologic Types of Lung Cancer, SEF.R, 19'13-1981 133 CJlcpts.13 Constancc P", John W. , Horni, and Thwar E Goffman Saeening for Lung Eincer. The Mayo Lung Project 61 CJia' ptet 14 Robert S. Fontmna and Willime F. Taylor Lung Cancer in japan: Effects of Nutrition and Pasuve Smoking 175 Chapcn 13 Taksm H'waymna Nutritional Status and Chemoprevention in Relation to Lung Cancer 197 Chapter 16 Peter Grenuuald and Willicm D: DrRw ritamin A and Lung Cancer in Louisiana 211 Chapter 17 13arbarn p 1.egwdew, alfrecro rvpa-s, and 1PAt iavx A John= Prevention of Smoking in Adodeacents: Current Perspective on a Sodal-Behavioral Intervention 19 Chapter 18 RicAmrd L Evmu The Biology of Lung Cancer vis-f-vis the Emerging New Biotechnology 229 Chapter 19 Merle Misell Transforming Genes of Human Lung N Grcinomis CO.D 235 N Geaffm 115. Cooper CJ CJ C~D N N G~3

A Cbapte.20 In vtro Studies of the Bialogy of Luag C.acer 247 ChaQtss 21 Deswnd N. (',m,uy, Adi F. Gatdar,, Frm,eir Cwtima, med JoAn A Mwia Radio.ctivity and Ggarette Smoke 263 ~'Jiapser 22 Tlwntai K We~trrs andfimteph R DiFranza Luag Cancer Inddence and Type of Cagarette Smoked 273 Chaptn 23 Persr N.Le4 Smoking Cessation Prograaa and Lnag Cancer 283 Ciaptes 24 ETkn R Grits Cancer preveation and the Smoking, Tobacco, and Cancer Program of the Nationil Cancer Lzstitute 97 ('Jiaptn 23 faseph W. C,d'lat Lung Cancer and Smoldn& ReSectioas and Unresolved Lwues 313 Frmtt L Wynder and Marc T. Goodrnmr Subject Iadent 323

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PtefCCA . TIu main cause of lung cancer is dgarette smoking; about that the saentific work repnrted in this book l'eaves no doubt. Approximately 90% of the deaths from lungancer and'almost one-third of the deaths from cancer of all kistds can be traced directly to smoking. In 1982, about 129,000 Amrrians died from smoking-rrlated cancers, according to estimates from the Office of Smoking of the U.S. Department of Heal th and Human Services. Buc ancer is not the only disease smokers have to fear: the habit also causes elevated rates of heart disease. According to research reported in this volume, about one in four rrgular cigarette smokers will be killed before their time by the habit. And the magnitude of the problem is greater than usually is rtalised': Of every 100 healthy young male smokers in England, statistia predict that one will die a victim of violent citae, two will be killed in traffic acddents, and 25 will die from a disease brought about by agarrttes. Similar proportions of deaths will occur in the United States. Women are quickly gaining equality with men in the lung cancer arena: in 19$2. lung cancer surpassed breast cancer as the leading cause of ancer deaths among women in eight states. The pattern, which is believed to be nationwide, is attributed to an increase in smoking which began among women 30 years ago. The cost for smokers is high in terms of dollars as well, as health. In Louisiana, where 2,100 persons die every year from lung cancer, more than $300 million annual'ly are spent on the purchase of; cigarectes and medical costs and loss of earnings account for approximately, iS86 million per year. Thestate--espedally its southern area-has one of the highest cancer rates in the nation, and many of the studies in this volume look at some of the reasons. Several papers demonstrate that smoking no longer can be considered' a personal habit concerning only smokers. Passive smoking-smoke inhaled' from nearby smokers-increases the lung cancer rate. Rexarch conducted in Japan has demonstrated that nonsmoking wives of heavy smokers suffer a lung cancer risk at least twice as great as nonsmoking wives of nonsmoking husbands. Research has also shown that radioactive materials are a common component of cigarette smoke. Other studies in the book explore the relation- ships of nutrition, smoking, and lung cancer: a precursor of vitamin A that comes from green and yellow vegetables can perhaps lower cancer risks. Smoking can work synergistically with occupational exposure to ancer• ind'udng agents to increase dramatically the risk of lung cancer. Studies have shown that some individuals may have genetic factors that make them more susceptible to certain environmental carcinogens. )d

Cigarette smoking is a form of d'rug dependence because nicotine u an addiction-catuimg drug. And cigarette smoking is knourn to ause cancer. The addiction to this toxic drug produces many times more deaths than addictions to tnarijuana, morphine, and cocaine combined. Yet those drugs are illegal. Why then, one may ask, are cigarettes advertised and sold all over the world? When cigarette addiction began about 60 years ago, its deleterious effects on bealth were not known because smoking-induced cancers can take as long as 30 years uo develop. Now, cigarettes are a multibillion dollar industry, with extremely well-organized lobbies and advertising efforts. Well over $1 billion: each year are spent on efforts to promote this addictive and deadly drug; that sum is more than the total budget of the National Cancer Institute. What can be done? Some of the research in this volume explores the alternatives. Abolishing smokin`, of course. is unrealistic, but other efforts bttld promise. Reducing tar 'un cigarettes may. over the yean, reduce cancer rates, but in absolute numbers, lung nncer deaths are likely to go on increas- ing well into the twenty-first century due to saturation marketing efforts and increases in absolute numbers of smokers. Public education efforts about the deadly effects of smoking are inadequate at the present time and could be made much more effective. And legislation-with higher taxes-can make a differ- ence. In Finland ambitious new laws were enaaed' in 1977: these laws prohibi- ted' advertising and sales promotion of cigarettes; forbade smoking in all public places except in designatedareas; outlawed the sale of tobacco products to persons under 16 years of age; reserved money from tobacco tax revenue [or developing health-oriented government tobacco policy; and made the govern- ment responsible for establishing the limits of harmful components in tobacco products. Finland now leads the world in reducing lung cancer deaths. espedalty in younger individuals. The bat way to change smoking patterns, which would automatiolly aEfett lung cancer occurrrnce, is to convince young people never to begin smoking. Parents must be aware of their responsibiliues as role models and sehools should make a health education program emphasizing the hazards of smoking a part o[ instruction from kindergarten through college. The college students fiom Tulane's Chapter of Alpha Epsilon Delta, recog- niting the hazards of smoking. helped with various phases of the conference and continue to sponsor antismoking actiwicies. In fact, plans [or this book began when Alton Ochsner became an honorary member of AED (the National Fre-Mediczl Honor Society). We were seated around a banquet table in a New Orleans garden district restaurant when the International Lung Cancer Update Conference was first discussed. Dr. Ochsner planned to present a short history of lung cancer at the conCerence. for as he told us ....... this disease has grown up with me. It did' not exist when I was a medicaf' student." Unfortunately Alton Ochsner died before the conference convened, so this volume lacks his historical perspective. Nevertheleu. this book is dedicated to the memory of Alton Ochsner and we were pleased to have his son. John Oehsner. participate in his stead. We gratefully acknowledge the continuing CID co ~ ~ ~ ~

sik aid of the student members of AED and' their antismoking efforts; as well as the help of Diana Pinckley; Director of Tulane Univenicy Relations, and her efficient staff for their aid in cover design and'various aspects of production: The organizers of the conference are especially indebted to Lorraine Mizell. whose untiring work helped make the meeting a success and whose concinu- ing efforts and administrative expertise helped produce this monograph. The conclusion is clear: cigarette smoking causes lung cancer. ff scientists and' concerned citizens can communicate that simple message to the public.. the cigarette advertising salvos and lobbying efforts may all be for naught There will then be hope of controlling this disease. Merle Mizell, PhD Pelayo Correa, MD

aclknowledgmenta I speak on behalf ofTulane Medical Centerwhen I~ say that we are pleased and proud that Tulane Univetsiry has served as one of the cosponsoring univenities of this International Lung Cancer Update Conference. It is fitting that this monograph be dedicated to the memory ofAlton Ochsner,. MD, an honorary alumnus of Tuiane School of Medicine. He served on the Tulane faculry for many years as professor and chairman of surgery, prior to establishing along with fourother Tulane department heads what has become the Alton Ochsner Medical Foundarion Dr. Ochsner, an internationally known sutgeon, dedicated his life to the elimination •of lung cancer. We have come far in the battl'e against lung cancer, but there is still much more we can learn about the etiology, prevention, treatment, and ultimately the elimination oflung cancer as a significant cause of human suffering. It is through participation in cooperative efforts such as this international conference that we hope to provide an exchange of information which will lead to even more answers about lung cancer. folnt J: Wats1. MD. CJiana{!o. TYlaru C-4sivers~ .4tedical'ftntn I am glad to acknowledge the success of the joint efforts of our institutions: Louisiana State Univessiry, Tulane University, Cancer Associ=tion of Greater New Orieans, and t!u Board of Regents in organizing and carrying out the International Lung Cancer Update Conference. The conference addressed an issue of gnnt impottance to our community and provided up-to-date prexntaaons by some of the best international experts in the field. The conference has already stimulated' important discussions in our scientific community and has established an objective scientific basis to approach the lung cancer problem in our state. I hope the impetus provided by the conference will continue until' a strategy for prevention is developed. Ala:+l f. LArson, MD, Lle+an Gctsuiana Statt Universiq ScMo!' of Medidne in Neto Or{wtsr The Louisiana Board ofRegents and its Advisory Committee on Research and Development are pleased to have had the opportunity to sponsor the Interna- tional Lung Cancer Update Conference. The state of Louisiana. its citiiens, and its institutions of higher learning are all beneficiaries of this meeting. sr

As a result ofbringing ;tie worid's authorioes on,.ing cancer research together in New Otieasts to presenr and euhange reseuch findings about the state of the att in this field, the world has seen that Louisiana is seriously concerned about this dread disrase and intends to promote soentific research in order to address this probleta.'Therefore the state's image with the srienti5c community has been eahanced worldwide. I,ou*a,'-na's dtizens have benefited Erom this conference because they received the most current and reputable advice from the foremost expests in the field about what they on do to enhance their chances of living lung-cancer-ftee liva- Tttey tearned that this discase is largely selE-inllicted. Finally the scholars, scientists, and medical practitioners in Louisiani s inst} tutions ofhigher learning, as well as the scientifu community outside our coUeges and univetsiiies, have benefited from the opportunity to exchange infotmation 'rith, ask questions of, and interact with the experts who participated in this conference. The Internationil Lung Cancer Update Conference was atremendous success, and we at the Board of Regents are aaremely pleased to have been a put of it. Nifllusa Aroen.au+4 PliD Canesissio+ur of FfigAe. £dueatio+s Lo+dsiara B_W+d ' of Regents Sponsoring a conference is an uncommon event for the Louisiana Board of Regrnts'Researeh and Development Prograrn. Generally only research projeas which address issues that are of particular concern to the sute (eg, hazardous waste, economic developmen[ wetlands, the st3te's high incidence of cancer) anr supported with these stste-appropriated funds. Since one of the goals of this program howeve.r, i's to upgrade the quality of research in Louisiana's instin} dons of higher learning. the Board of Regents and its Advisory Coatmitue on Research and Developmetu decadedthat sponsorship of this conference not only was appropriate, but also would be a decided investment in the future of quality cancer texarch in the state. In sponsoring :his conference, the state provided its scientists a rare and perhaps unique opportunity to learn from and exchange ideas with the world's foremost authorities in the lung cancer field in a convenient iocuion and forutn. The knowledge and information the state's sciendsts gleaned as a result of thu conference should stimulate interest in this area. as well as promote the submis sion of research applications to the R&D Program that are at the forefront os knowledge in this field. The response to this conference from the Louisiana scientific and medica communities was overwhelmingly positive. The Board of Regents was fortunscc that the organizenofuhe conference were responsible and talented individuali who undertook this task in a serious and dedi:ated manner. Their hard work anc combined talents, in conjunction with the outstanding speakers and excellen soenrific presennaons, made the conference an unequivocal success. On behal 0 N

of the Board' of Regents and its Advisory Committ.ee on Research and Deveiop- ment> we thank these individuali for their contributions not only to the R&D Program but also to the continued a&znt emenc of knowiedge in this state. Indlla Kilc:eate, PAD, Derscsor Ra.mrh and Det's1oP"uw Aag+ louuicna Board of Regertu The Board of Directors and saff of the Cancer Assodaaon of Lo+=s=RaInc. and'the Cancer Assodation of Greater New Qrleans, Inc, a United Way agency, are very proud to have been involved' in the planning and coordination of the Intrrnational Lung Cancer Update Conference held March Sb, 196l. Many ofthe papers presented in the monograph reviewed the smoking habits and' the epidemiologic trends in lung cancer incidence and mortaliry in the United' States, Europe. and Japan. TZtey all repeatedly emphasized the impoT- tance of dgareae smoking as the major causative factor in lung cancer. Environmental hazards (eg, air pollution and asbestas) and host faaoes (eg. geneacs and nuaition) play a small role in the overall etiology of lung cancer. The most important conclusion of the Interstational Lung Cancer Update Conference is that an intrrnational emphasis should be placed on smoking cessation programs aimed not only at high-risk adult populations but more importantly at aU adolexerna The only rational approach is to prevent lung cancer by graing individuah to either sop smoking or never to start to smoke dgaretses. RoMt G WeilaaaJrer., MD, Preident fawuf A'ssocianon of Greoler .ti'ety Orleant, Inc f:araes Auociation of Loui:iara, Inc With the high inddence of lung cancer in Louisiana, it was very appropriate forNew Orleans to be seleaed' as the host city for the International LungC.ancer Update Conference. The Cancer Association of Louisiana and the Cancer Association of GtraterNew Orleans are glad to cosponsor a conference that brings together some of the world's lung cancer experts • Personally, I have appreciated the opportunity to be involved' in a program that could help resolve some of the health problems of Louisiana's citizens. Ruth A SAnxaood Era+cvtiw Di+.csor Caraer Avooatioa oJCns,ater 1Veto Ort.anr, Inc Canar AssodQabR of Louiriasta, Inc

I C HAP7ER 7 The Causes of Lung Cancer In Texas PATRICM A BUFRER.` UNDA 1NlLlJAMS PIME•• 1HOMW .l: AM.SON:" ond CHARLES COllfANT`• ~ Epidemiolosy Rmeuch Utut. The Univenity of Teaa. Health Science Center at ]iouaon. Sehod of Publir Heilth. Hou.toe, Tesa. 77025 •'Environreentai Epidemio{ogy Eranch. tHationa1' Cancer Inuitute, Lndow 3C]S. Benhesda. Maryland 20205 ASSMCT A popularion•ba.ed case-comparison inte++riew study of lung cancer was conducted from 1979 to 1982' in six Texat coastal countiea-Orange, JeSerson, Chambers, Fiuru, Ga1- veuon, and Brasoria-to evaluate the asxxiation of lung cancer with ocrupuional'and other en.ironmental exposures. Lung cancer mortaliry rates in these counties consistentlv have ex- ceeded lung cancer mortality rates o`»erved for Texaa and the United States from 1950-1969 to 1970-1975 for both sexes and races (white and nonwhites). Fiistoibgically and tytoiogicslly confirmed incident cases diagnosed during the interval July 1976 rtto June 1980 among white male and female residents aged 30-79 years were a.eer- tained from partiaps<ing hospitals in the six-counry area. Both popul*tion-based and de- cedent eompuiaons were selected and matched on age, race, sex, region of residence, and vital aatu>t at time of aacertainment. The exposures of pnimary interest in the study of lung cancer are those auociated with oc- cuparion (employment in specific industries and ocrupation>t):in conjunction with tobacco, almaol„diet., and residencial exposures. Rey Wo.dr: Smoking history, penocbemical iaduatr7, &iatologic types, constrstetion wrken, chemical manufacturing, tnasporsation Introduction and Background Data presented by DoU and Peto (1) and related reports (2) indicate that respiratory cancer sites„ dotninated by lung cancer, show the most dramatic in- F creaus of all cancer sites over the patt 30 years~Tlte~role of:moking in the etiology ,~, pf respiratory cancer has been well docuaunied LIn addition, lung caneer is L qt verbp C'+.*r ~+wrvhv+a[ r+e t+n0 CCnesr Cass on0 PVM+w+ 83 N0T1CE Thts matetial may W protected by cOCyright in (TttA 17 U.S. Code).

Pafrido ~l 9uMSW. LnOc VWior+u Rlt:klr. thornos J. Moson sr cl recognized as possibly the most important work-rrlated' cancer. However, the in- teraction between smoking and octvparional exposures and the increased risk that may be attributed to an occupational exposure has not been very.vell~rharacterssed for a largr number of woricplace exposures. A population-based case-comparison interview study of lung cancer, obtaiaing detailed occupabonal histories, was conducted in six Texas coastal counties where ltmg cancer mortality rates were elevated (3). Figure 1 shows the location of the counties of Orange, Jefferoon, Chambus, Brazoria, Ga]Leaton, and Harris, a highly industrialittd area where Houston is located. Approximuely 25 %(3.5 million) of the total stsce populadon in 1980 resided in this southeastern coastal area, the majority (77. S 96 ) in Harris County.. Newfy diagnosed, histologically confirmed cases of lung cancer in white females (induding Hispanic) were aaceruined frotn July 1977 through June 1980 in Harris County (3 years)~and from July 1976 through June 1980 for the surrounding five counties. Similariv, cases among white males (including Hispanic) were ascer- tained for four years (July 1976 through June 1980) for the five less urban but in- dustrialized counties, excluding Harris County. Background lung cancer mortality rates for white males and' females were examined by Texas State Economic Area

Tn. Cms.m oa Lurlp Ccsnc.r n Trxos gs. ~ Top 10N.1Siqnof >U.S. ® Low 10w.rSlpnd < U S. Not ToC 10'h/Sipntt >U.S. ~ Not Low 10Y.1Spnt1 < UIS. O Not &qnificantly DiftfrMt Frpn U.S. Fi~urc 2. Lung cancer mortality, 1970-1975 for white mala. (SEA) for the time period (1970 to I975!) irnmedisteJy preceeding the case- comparison study. As shown in Figures 2'and 3, these maps consisuntly document the significantly higher lung cancer mortality rates observed earlier for both white males and white females in these Texas coastal counties. The dark areas along the upper Texas coast are the Beaumont SEA (Orange and JefTerx>n counties); the Houston SEA (Harris County), and the C`,alveston SEA (Ga1.•eston County). Age- adjusted mortality rues (adjusted to the 1960 United States population) in these areas are in the top 10% of rates for SEM in the United Stues and att signifiwntly higher thaa the white male or white female lung cancer mortality raee for the total United States population. For white females in Harris County, this excess was notahJe for both the tate and the tread' in the rsze from 1950 to 1975 (4). For a11 ages, combined, the overall exeas ia lung cancer saorsality in the Texas study ares is approximately 30-40 46 , but this is considerahly greater for some age groups. Occupational and industrial exposures of iuaporunce for residents of the Texas coastal area include those associated with shipbuilding and repair, chesaical and 'Fxciu"g deuAs for 1,M.

86 PCfrlCio A BUPRw. Lfn00 Wfiarns PICIW. ThornCS J' MCSOn *t at  Top 10N.15iqmt >U:S. ® {.ow 10Y.1Spnrt s U:S. 0 NOt Top 1'0'h'lSqnrnf -U.S. a ' Not Low T0'/.1$iynrt <U.S. 0 NCt Sqniticantfy Dittorent From U.S. 1<'>;uec 3. Lung c.ancer mortaliry 1970-1975 for white females. pec:.hemical manufacturing, petmleum refining, conatrucrion, and metal in- duatries. The largest T:nited States based chemical and synthetic rubber production fasilitiea art located in the study area, so a high proportion of the working popula- tion currently is employed or -hu been employed in dsese industries. For some of the smaller counties, such as Orange andjefferson, where a single industry is dominant, as high as 2796 of the working population reported~ being currently employed in chemical and allied products manufacturing compared with 2% for Harris County (5).. Methods Histoiogically confirmed incident caaes of lung cancer diagnosed among white male and female residents (including Hispanic) of the study counties for the designated tirne intervals ( Juiy 1977 througfi June 1980 for females in Harris County and July 1976 through June 1980 for rnales and females in other counties) were ascertained by review of hospital and state records. Hospitals in the study area that were not already participating in the Statewide Cancer Reporting Program

Tt,. Couss ot Lunp Conc.r n T.xcs 87 ,,erc contacted and'asked to partitspate in the study. Populuion-baxd and dece- dent comparibon subjects were sdected from state and federallreccrds and matched to naes on age, race, sex, vital status at time of aacertainrnent, and county of taidence (Harris County or other five counties). Hispanic study subjects were identified systematically by use of an algorithm to identify Spanish surname. Jv[edical~ records were abstracted by state-trained abatracton to obtain relevant disease and demographic data. Following contact with the family physician (for caser only), personal interviews were conducted with study, subjects or with the next of kin of decedent caaea and comparison subjects, using established criteria for selecting the most appropriate next of kin respondents. Interviews were conducted by trained interviewers in the bome using a standardized interview prococol. Detailed inform:tion regarding the primary exposures of interest was collected, specifically smoking history, work history,, residential history, and drinliing history. Industries of employment were coded to the Standard Industrial Classification (SIC) (6) and occupations were coded, using the Diettcnory of AuYpationa! Tit/v (7). The Mantel-Haensze] summary rhi-square and odds ratio ttatistia were caiculated (8). Confidence intervals (9596) were calcvlated using the metfiod~ of Miettinem (9). Results A total of 56 of'the 67 hospitals in the six-counry Texas study participated in the study, including all of the seven large hospitals (300 or more beds). Ten of the 1I mmaller hospitals that did not participate were located in Harris County. Tbertfore we were able to ascetvirt 92.2% (1520'caaes);of the total 1649 incident white male and female lung cancer caes (including Hispanic) estimated for the 3- to 4-year in~ ternl (mid-1976 or 1977 to taid-1980). The number of incident cases was esti, mued by adjusting age-race-sex-county mortality rates by population growth and an incidence: mortality ratio of I.3S:1.0: Case ascertainment was higher for resi- dents of counties other tlian Harrie County, 97.296 vs 82.196 (Table 1). A toal'of 766 female and 754 mak cases were ascertained representing, respectively, 88.7 and 96.1 % of the total estimated incident cases ascertained Hispanic females ap- peu to be pootay ascertairted~(38.196)„ but this may be related to the clavification based on Spanish surname which may not be an effective technique for ascertain- ing married Hispanic females. All ascertained eaaes will be used for determining age-race-sex and county lung cancer iacidence rates for the study area. A total of 88.9% of the ascertained cases were included in the interview study. Some cases (110, or 7.2 °J6 ) lacked histologic or cytologic confirmation of husg cancer and were ineligible for the case- comparison study. For the majoriry.of tbese cases (79, or 71.8%) the basis of the lung cancer diagnosis was radiologic or clinical evidence. There was inttufficiertt diagnostic information ava0abk on the remaining 3t cases. Additional lotssa of study subjects in the casr-comparison study were related to race and residential eligibil;ty tsiteria; unable to locate; moved out of interview area; physician,

88 potrtitq A. eum.r. Ur,do wftrnr aticlcl.. Thomc.+ J naoson .t a Table 1. Lung cancer case axertainmene in Texas study , by mx, ethnic group, and ara, 1976-1980 NMbv 1'taafbv :Voaber .ri.ae.d' .eeasas.d` ( S. ) caees inter.i.+.d~ White Femake Angio E22 750 (91.2) M9 Spani.b suuname 42 16 (3l.1) 11 Total ~{ 766 (8a.7) 460 W6ite Males Aado 767 730 (95.2), 460 SpeaiaA aurname 1! 24 (133.3) 15 Total 785 754 (96.1) 475 Area Hu*i. County 567 468 (t2.1) 275 (kmaJfa trnlj+. 1977.1960) Other counties 1032 1052 (97,2), 660 Total 1649 1520 (92:2) 935 t alnefude t 20 e.aas..atAout hmoioqr c onfirnuuon aaid e n add,uoftel I! cae c+tuemed te b e wni¢bk. mtatea ol ~r..acr~-•~udrendene: mterv •ude+.cast inefipbW n«locned. refua.Ubyphvaac b ue hoqna J!.or.rudr.uDyV . and caaenime+ne.adatd mubaquentlv 4rnttfied ar kndipbFk. a..dawto tieo!'pc or 9u.iny. .. Table 2. Texas lung cancer stud,v population by sex, study group, and ethnicity I 3-d7 i-P Caees Csatrol. T.tal. Total Female fli0 482 942 Male 475 166 941 Totai 935 948 18d3 SpaniaA surname Female 11 20 31 Male 15 19 34 Total 26 39 65 hospital, and subject refusals; and poor quality interview data. Overal) study sub- ject refusal rates were 7.7% and 10.7% for decedenl caxs and controis rrspec- tively, and 13.546 and 20.646 for living cases and controla, respectively. A total of 935 interviews was completed with eligible cases (460Amales and 475 males) and 948 interviews with frequency matched comparison subjects (Table 2): Included in these totals are 26 Spanish surname cases and 39 comparison subjects. Separate ana]yses are not ptzsented at this time for these study subjects. The average duration of time study subjects resided in the county of diagnosis or in the six-county srudy area is over 25 yean for all study groups. The majoriry of both male (86 %d ) and female (82 9fe ) ~ cases were decedent cases and were slightly older at time of diagnosis than the living nses (Tables 3 and'4), The distribution of age at diagnosis is compared for male and female study groups in Figure 4. A higher proportion of the female caxs was diagnosed ~ before age 60 (45:4 4b ) ~ tAan male cases diagnosed' before age 60'(34%). I ftJ

Tn* CoLss ot Lurq Conca h T.xos 09 Table 3. Number and percentage of male lung cancer cases by age at diagnosis and rype of respondent, Texas, 1976 to 19E0 T7Pe of respos,des+t Toal Sdt Nost of lia A8e .e Caoe Ce.vola C..a Coasals Car. Co.trels doPosi. (Yov.) No 96 No S No S No 9. No % No S 30-39 1 1.5 1 1.6 3 0.7 2 0.5 4: 01 3 0.6 40-49 5 7.5 7 10.9 26 6:9 34 8.5 33 7.0 41 8.8 50-59 23 34.3 22 34.4 102 25.0 98 24.4 125 26.2 120 25.7 60-69 31 47.0 ~ 23 35.9 165 40.4 164 40.8 196 41.3 18.7 40.2 70-79 • 7 101 11 17.2 110 27:0 104 25.9 117, 24.7 11.5 24.7 ~ 100!0 100.0 100.0 100:01 100.0 100.0 t Towll 67 64 408 402 475 466 Table 4. Number and percentage of femak lung cancer caaes by age ar diagnosis and type of respondent, Tecas, 1976 to 1980 T7Ps of r.opo.deat Taal 1 8df Nest of kia Ags s,t cam ConwL Coies Cosuoi. Ca.e. Coeaol. "8- (rean) No S No S _ No S No % No S No '1< 30-39 0 0:0 3 2.6 6 1.6 5 1.4 6 11 8 1.7 40-49 9 11.1 12' 10.3 40 10.6 110 13.7 49 10.6 62 12.9 50-59 36 44.4 55 47.4 118 31.11 104 28 4 154 33.5 159 33 0 60-69 24 29.6 34 29.3 153 40.4 135 36.9 177 38.5 169 35.1 70-79 • 12 14.8 12 10.3 62 16.4 72 19 7 74 16.1 84 17.4 100.0 100:0, 100.0 100.0 100.0: 1W0 Totalr 81 116 379 366 460 482 Proportions of male and female cam and compariaon subjeas using tobacco, cigamtes, alcohol, or who "ever lived' with household member who smoked regularly" are compared in Table 5: Ninety-seven perctat of the male nses and 9196 of the feraaTe casa reported,ever smoking cigarettes but a higher praportion of the female tltan male cases reported smoking cigarettes currently, 68% vs 5496. Proportions of heavy unokeri and use of alcohol (ever) were higher for cases tflaa comparison subjects and for males than females. An exvandy high proportion of both female cases and' comparison subjects report having lived with a household member who amoked regulariy, 93% vs 88%. Althouglt the patterns of risk difTered for males and females (Table 6), the odds tnrios for all srnoking variables were statinicaIlv signiGcant at the p•.05 level. Among males, ex-smokers had a risk higher than current smoken, whereas in females the risk was lower in ex-stnokers. The liighest odds ratio for fcmales was observed for current smokers, 7.9 vs 5.0 for ex-smokers. Odds ratios for the ac- I

90 PCfrIC~o A&1f'M1K: L'r+CiC WiQnns PICk*. ThpMCS 1 AAOsC, _-r• Xw~ au~ ua nr r.o 41.7 I ta 0+0. \ a0-3. .a.. sa.. .oe. rn.. ..,,rw _ ae. . o~.....r fignre 4. Age distribution (age u diagnosis) for male and female studv subjects. Te:as luns cancer study, 1976-1990. Clear columns. cases; shaded colurans, controls. curnulated lifetirne agarette dose, expressed as pack•yean, were higher for males in the low and moderate categories but associated with a similar gradient in both males and females. No difference in risk was associated with the use of filtered dgarettes for either males or females. The role of "patsive smoking" in contributing to risk of lung cancer was exartt- ined (Table 7). In this analysis the crude ior unadjusted) odds ratio are increased and signi6cantfor both males and females. 1.4 and 2.1, respectively. However, when the confounding effecn of individual'subject smoking was controlled' bv stratifying the Table S. Proportion of cases and controls reporting use of tobacco; cigarettes and alcohol by sex„Texaa lung cancer study; 1976-1980 kales remales Caan CesrreL Ca.er Garrol. Tobacco (ever) 0.99 0.90 0.91~ 0 59 Cifaresta (em) 0.97 0.80 0.91 059 Ciprettea (current) 0.54 0.47 0.68 038 Ciprettes (light) 0.08 0.10 0.05 0: 17 Ciptettes (heavy) 0.45 0.29 0.34 0.13 Akdsd (erer) 0.86 0.81 0.78 0:63 Lived with a smolKr 0.76 0.70. 0.93 0;88

TTr Caw.w of I:unp Corca r Te:os Table 6. Odds ratioi auociated with smoking variables 91 for malet and females, Texas tung cancer study, 1976-1980 Male Ie.ale Ever .moked 10.12' 6.89 Carrent trnoker 9.99' 7.89 E,.®oket 10.85 5.00 r,tk•reAr+ Low (t)-3s) 6:24 3.21 Mcderace (36-63) 9.39 7.96 HigL (b4 • Y 13.05 13.35 Fihend cigartnes Yes 9.39 7.11 No 10;23 6.06 Doth 12.27 7.09 'MD', oddt ntwo .pJcann r p <. .05 male and female study groups into smokers (ever) and nonsmokers (never)~andex- amining the adjusted odds ratios, there was no significant incrxax in risk a»ociated~ with passive smoking. In fact, the odds ratios for nonsmokers living with a regullv smoker were not increased for either malts or females, 0;52'and 0.78„respectivdy. However, odds ratios for smokers living with a trgular smoker were increaaed, al- though not significantly, 1'.28 and 1.80 for males and females. The overall odds ra- uos (adjusted) associated with passive smoking were only slightly increased and not signifitint for either males or females, 1.2 and 1.3, respectively. When the possibility ofa "passive smoking"efiea was examined among nonsmokers by number of years lived with a regular smoker, there was very little difference in risk for females who lived with a regular smoker for 0-32 years (Table 8). Tbe odds ratios for rrtales sug- gest an increax by are based on smaller numbers tfiart the analysis in females. Table 7. Odds ratios for pssive smoking (household member smoked regulariy)iin Texas male and fena)e lung cancer studies, 1976-1980 Yes N. 0" 9s !. Ca.e Contrd Ca.e Coavel eatio Coafideace iistererall xe Males Crude 363 329 93 119 1.41' 1.04, 1.92 4.8 Sdfever tmoked No 5 56 6 34 0.32 0.15, 1.74 1.2 Ye 357 273 87 . tS 1.26 0.91, 1.79 2.0 Overall (MOR) 1.20 0.87, 1'.63 1.18 Females Crude 429 425 24 51 2.12' 1.29, 3.50 9.05 Self ever naoked No 33 164 8 32 0.78 0.34, 1.81 0.3 Y" 396 260 16 19 1.90 0.92; 3.58 3.0 Orerall (MOR) 1.30 0.78, 2.18 1.0 . p < .03. I

92 ' Pofr~o A ktrw. Lrido VYaat*+s Dsckli. Thor.~s J Moson at ol~ Tabie 8. Odds ratioi associated with passire smoking lVW U.e with LeoeeLe+ld sshar .!e ssokad Nesber Oid. eatio ConSdeeu iater.el Male. Tod'nonamokers 61 0.52 0.15, 1.74 1.2 0-32 rean 49 0 40 0.10. 1-58 1.8 33. yean 10 1.56 0.30, 8.05 0.3 Fem.is Total'mnsmol 201 0!78 0.34, 1.81 0.3 0•32 g.rs 97 0!62 0.24, 1.63 0.9 33. yean 99 0.93 0.38. 2.28 0.0 Histologic types of lung cancer were vasaified according to the World Health Organization (WHO) classificstion (10). The four major cell types account for 75-85% of the cases in both the malt and female series and the cellitype distribu- tion by age group is shown for males and females in Table 9. Adenocarcinorna iu the predorainant llulg cancer cell type in both young (30-49 years) males and females, comprising 37.8% (males) and 38,9% (females) of all lung cancers among pe-sons aged 30-49 years at diagnosis. There is a marked shift with a$e in this pat- tatl such that for both males and females aged 70 or, older at diagnosis the predominant cell type is squamous or epidermoid (accounting for 40.5% of all cases among males and 31.0°k among females). Overall, squamous was the predominant cell type among males (42.2%)',and adenocarcinoms among femalea (35.5 96 ). , These patterns held for both smokers and noasrnoken except for nonsmoking males, in whom 6 of 11 ('54.5%) cases were adenocardnoma. The risk associated with smoking was examined by cell type, specifically odds ratios for srnok.ulg categories withitl the adenocartinotna series compared with nonadenocarcinoma cases (Tables 10 and 11).. The odds ratios for smoking categories based on pack-years were allisignifcant, ernphasizing the increased risk of lung cancer (all types) associated with smoking. However, the gradient of ruk, in both males and females, was markedly diSerent for adenocarcinoma compared with nonsdenocarcinoma (all other king cancer) cell types. There were 104 cases of Table 9. Male and female luns cancer cases by histologic type and age. Texas. 1976-1980 1119" Eem.ls 30-49 yurs 30-69 7ears 70- ytan 30-49 years 30-69 .ean 70• yean CsII tm N. % Ne 76 No !4 No 94 Ne !b No 1i Squunotu 8 21.6 112 34.8 47 40.5 11 20.4 74 22:6 22 31.[l 9tnall cell 4 10.8 64 20 1 16 13.8 10 18.5 92 28 1 11 15.' Adenocateitwma 14 37.8 73 22.9 17 14.7 21 38.9 99 30.3 19 261 Lrr cdl 2 5.4 19 6:0 9 7.8 4 74 ' 1 l 3 4 3 4: Other 24.4 16.2 23.2 149 15 7 12:: ' Total 100!0 100:0 100.0 1000 1000 1001

T1,. CoWSfs of Lurg Cm+c.r r, texas Table 10. Odds ratios associated with smoking for lung cancer cell types in males, Texas lung cancer srudy, 1,976-2980 93 C~a't7P'e S.wkiag c.tegery (Pack-7w*) Odds e.[io Ce.bdeuee ister.ala ~ Adenocarstnoma Low 3,85 1.44; 10.31 8.04 Maderatt 4.45 1.72. 11 s 48 10.93 Htglt S.3d 2.14. 13.56 6 15.21~ 1Sonadenoca+rinoma l.ow 6.60 2:75; 1,5.l4 21.57. Moderate 11.30 4.87, 26:19 43.75 Higi, 15.41 6.73, 35.25 63.34 Table 3 1. OQdds ratios associated with smoking for lung cancer cell ty,pes in females. Texas lung cancer study, 1976-1980 I Cell rype soeking eawefory (yaei•ysar.) Odd.. e.tio Coefidesee ieeen.it 7~ Adenocarcunomr Low 2:16 1.1a, 3.9E 6.37 Moderate 4.32 2.40. 7.79 26.11 )ayh, 7,50 4.28, 14.20 52.93 Aionadtnocareinoma Y.ow 4.17 2.34, 7,43 25.90 Moderate 10:97 6:27„ 19.20 9647 High 1l:90 10:61, 33.67 126.13' adenocarcinoma in the male series and: 139 in the female series. A much steeper in- crease in risk associated wiih lifetime cigarette dose (pack-years) is observed for a1 other lung cancer cell types compared to adenocarcinoma. 'I21ese patterns are sum- taarized in Figure 5. Preliminary analyses of the detailed work histories i= based on the usual occupa- oon and usual industry of employment as reported or as sumraari:ed from the work hittory for self and spouse. Fxarnination of the work histories indicates that approximately 78% of the study subjects spent more t2iarl half of their reported working time employed in the occupation reported as their usual occupation, Utual industry of employment was determined by selecting the industry in which, a sub- ject was reported to have been employed for the longest duration of tirae. OdF4s ratios, adjusted for smoking (everJnever) were determined' to identify whether an increased risk was associated with employment in a given occupation or industry for both males and females. Using the ProfessionaUTechnical~category as a referent for males (odds ratio - 1), none of the odds ratios for the other occupationat categories was signiftcarrtly inareased, (Table 12). Odds racios (OR) for uawl in- dustry of employment were sii;rsilarly calcvlated tszing the saks category (SIC 50-59) as the referent (OR - 1.0) (Table 13). Significantly elevated odds ratios were observed for seweral industrial categories, speeificaDy eonscruction (SIC 1'5-17),,rbemical manufacturing (SIC 28), rnetalirnanufacruring (SIC 33-34), and transportation (SIC 40-49). In addition, an elevated odds ratio (OR - 2.44) of borderline statistical significance (at the .051eve1) is observed for oil and gas exnac- tion (SIC 13). I ~ N W C.1 ad N N ~ ?V

94 PQtPfCiO k BUffw ; id0 WiOmt Pkk*. ThprtiOs J. MCsCr1 sf at aao aD ,p R ~ t, oJT RIf .0R R RR % Ktt01I % G -...,.....~... p ' .__..r.~....ra..~...® ~• _ ... ..,....,.,.,.,e S , _._...,....~.~..~ %% N171" G1aH - (L,A ~•.: ,4 a Mtmmw "W% MraMyCr.MNfhrr•1Yiy. 1 igure 3. Odds ratios a:sociaued with arnoking by lung cancer cell type. Thc majoriry (appro:draately 60%) of the females reported their usual occupa- tion as houaewife. Using this category as the referent (OR - 1.0), smoking- adjusted odds ratios (ever/never) were calculated for the remaining categories (Table 14). Although there are scveral categories with devaurd odds racios, only the odds ratio for the cierical category (1.57),u significant. The odds ratio for the serv- ice category (1.57) i's similarly increased, and of borderline statistical: significance. Table 12. Adjusted' odds ruios for usual occupacion in Texas maJe lung cancer studv, 1976-1980 Oerop.tien caeego" Total naabe: in catetor= (caae and controle) Odd. ratio Coofidknce inter.al xt ClericaVS.ks 94 0.61 0.36. 1!.04 3.33 Service 50 1.12 060, 2.09 0 13 ABriculture 39 0.89 0.44, 1.84 0 09 Proce.an8 77 0.30 0.47, 1.38 0 63 Machine tradea 77 1.37 0.78. 2.39 1.19 Dench work 14 1.0f 0.34, 3.19 0 0. Strstctun! .+ork 275 1.46 0.96. 2.20 3 15 Miacellaneous 140 0.89 0.55. 1.44 0.22 Profesionalrfechnii:al 157 1.00 - - - •Mju.ed fer vwt+nl few~ee.er). ~

Th. Caumes of Llrip Caic.r in Tsn 95 Table 13. Adjurted' odds ratios for siual indurtry of, emplovment in Teuaa nsale lung cancer study, 1976-1980 1.do.v7 eatKor7 (SIC eoEer) Tneal ass.r i. csetorr Odd+ ratis Caa6deece i.tt.al x8 Agncnhurt (01-09) 30 1.64 0.70, 3.83 1.31 piLBn csnct (13) 28 2.44 11.00. 5.97 3.82 (kbcr,.muunz (10-12, 14) 8 0.72 0.19„ 2:80 0:22 Conrtructwn (1J-17) 1!0 2.Se 1.49, 4.41 11.50 C6emrcsl(28) 60 2.1e 1.10, 4.24 5.04 Pesraieam (29) 178 1.54 ° 0.91, 2.60 2.63 Metals (33-34) 25 3.38 1.36, 8.39 6.90 Sh,pbuilding (373) 27 1.91' 0:83. 4.42 2.29 pt6rr manuhcrunng (20-39 minm above) 52 1.55 0!77, 3.12 1.51 Taa+porsacan (4l1r-49)i 120 2:57° 1.47„ 4.52 10.88 Pvsonal wvice (60-b9, 65 1.73 0,91„ 3.29 2.76 80;,91-97) Profmnonal/Govammental (70+79, 81-87) 65 1.34 0.77, 2 44 0:91 yle (50-59) 97 1.00 - - - ~.4dluw.d lor smok+ng (e.vNpe.er). ~P < .05 TaWe 14. Adjusred' odds ratios for usua)!ocrupation in Tesas female lung cancer .rud'y, 1976-1980 C7erical 161 1.57' 1.07, 2.31 5.27 Serv= 88 1.57 0.96. 2.57 3.22 AQietdrure 3 0.74 0.14, 3.92 0.12 ProusWng 2 4.22 0.43, 41.33 1.53 A4.cbiae trade 2 2.66 0:45, 15.93 1.15 lkncb work 11 1.67 0:47. 5.97, 0.62 Structura! 2 5.22 0:79, 34 59 2.93 %li.cellaneosu 8 2.27 0.52, 9.96 1.18 Pro(e.nonallf'echnw! 110 1.15 0.75,, 1.76 0.40 Houae+rife 551 1.00 - - - :Aerr.d tor. mI ie+eriee.yr). .<.05 'ibese were too few ob.etvaDoni in the remaining categories for a meaningful anaiysis. A similar analysis of usual indusey of employment for females indicated no categories of eoncern except for the possible exception of the increase noted for the category of other manufacturing (Table 15). Smokiag•adjusted odds ratios were also examined for the usual occupation and industry of employment for the spouses of both males and fentales. The only significantly inceased odds ratio observed was for the usualI industry of errsploy ment for spouses of female lung cancer casn.,T'he Construction industry, with 145 cz+es and eontrols reporting this as the usual industry for their spouse, was auociated with an increased odds ratio of 1.74 (1.04, 2.92; X4 - 4.40). I

96 pahkaa A BuMM. lYido Wioms pkkis. Tltomm1 AACSor, ±t CI Table 15 - Adjusted' odds ratios for usual industry of employment in Texas female lluls cancer study, 1976-1980 Iadu.try Total autsbv aategory in wsgory Odds r.tio Con&ieau iater.il zt Agricuau+. 6 0.91 0.24. 3:53 0 02 OiUps ear.c1 4 2.01 0.37, 1014 0.66 Ckder miiung 0 - - - - Lon.truction 2 4.95 0.75. 32:69 2.76 Cbemtcsl 2 3.93 0.40, 39 06 1.37 Petrvleum 6 0.43 0.91. 2 00 1.16 lwtetab 2 3.93 0.40, 39 06 1.37 Sltipbuilding 2 3.93 0.40. 39 06 1.37 Other enanufaetunn6 23 2.70 0.95, 7.67 3.50 Transportation 12 0.76 0.22. 2:76 015 Services 74 1.26 0.75. 2.13 0:75 AofeasionaUGovernmentali 93 1.08 0.69. 169 0:12 S.les 113 1.23 0.80. 1.90 0:92 Houa..ife 592 1.00 - - - yAdjue.d for vtwWnt {e.erinew~. Table 16. Odds ratios for household' member re3ulariy employed' in specific industry for Texas lrang cancer study, 1976-1980: Males Yw 93% Isduset7 Ca.e Costrol Odds ratio Gonfidkac. interval zt Asbestos manufacturinS 6 2 2.60 0.60. 1E25 1.76 Cement manufactunn; 5 5 0!99 0.30. 3.25 0 00 Insulation manufacrunnS 4 1 2.99' 0.47, 19.04 1.4N Coal mtning 11 4 2.57 0.56. 7,71' 3.06 Shipyard/tAipbuilding 56 52 1.11 0.75. 1.65 2.27 Demolition 5 3 1'.54 0.40. 5.93 0.41 Hi;It-rise corutruction 11 9 1.19 0.50. 2.84 0.16 Table 17. Odds ratios for household member regularlv emploved in specific industry for Texas lung cancer study, I976-1990: Females Ye. 9S % I.dustry Case -Control Odds ratio Confidence interval xt Asbestos mauufacturing 3 10 0.55 0.20. 1.90 1.29 Cement manufactunns 20 I! 1.17 0.02. 2:23 0 24 Insuluion manufactunnf 9 4 2.24 0.73. 6.94 2.07 Coal mininS 7 12 0.63' 0.25. I 57 1.00 Ship,vard/shipbuilding 99 102 1.02 0.75. 1.39 9' 0 02 Demolition 3 7, 0.77 0:25, 2.33 0.02 HiSh-nse construction 37 26 t.S2 0:91.,2.55 2 60 In addition to these analyses specific questions were asked regarding whether anyone in the household ever worked in the following industries: asbestos, cement. or insulation manutacturing; coailmining; shipyards and shipbuilding; demolition; N ~ c..w ca on I'J N ~ G~i

The CotisM of Ltnp ComCar in Taacot 97 high-rise construction. For both males and' females a large number of caxs and controls reported having a household member employed in a tttipyard or in ship- building, but this was not associated with an increased odds ratio (I.II for males and 1.02 for femaJes) (Tables 16 and 17). Among males there were no statistical}y significant increases; however, the odds ratios for asbestos manufacturing, irtsula- tion taanufaeturing, and coal mining are increased. Similarly, for females the odds ratio is increased for insulation manufacturing and high-rise construction but not agntftcantly: Discusslon The availabiliry of fairly large numbers of male and female incident lung cancer cases and comparison subjects in an interview study with detailed occupational histories provides an important basis for examining the contribution of occvpa- tional exposures to lung cancer in males and females. Recognizing the strong in- atase in lung cancer risk associated with cigarene unoking„such analyses need to control for smoking differences. Our preliminary analysis of usual occupation and industry of employment with a broad smoking adjustment (ever/hever) indicates iieveral occupational and industrial associations that need to be pursued in future analyses. Specifically, odds ratios are significantly increased for usual employment ' in several industries (conswction, chemical, metal, and transportation) for males and the clerical occupations for females. In addition, there are seYeral'•uw-+a*ti^ns suggested by increased odds raoos, which are not statistically significnnt. For males, an increased risk is suggested for occupations in the strucrural category and employment in industries related to oil and gas extraction (SIC 13); petroleum refining (SIC 60-69), and shipbuilding (SIC 373): For females„occupations in the service category and industries in the other manufacturing group are associated with fairly stable increased oddt ratios. Future analysis of these data will examine the possible interaetion of smoking with occupational and industrial groups and a possible need to employ more specific smoking strata. Examination of odds ratios for smoking strata within oc:. cupational and industrial categories svggested' that an ever/never smoking dassification would be sufficient to control!for the confounding elfect of smoking in the examination of overall risks associated with usuaJ, employmenr in specific oc- cupationall and industrial categories as presented here. However, this broad rlassification may not be sufticiently specific for an exarninatibn of interaction of smoking with workplace exposures. In thes+e analysn the classification of •`expoaed•` witAin a specific category is based upon the "tuual" occupation or in- dustry of employment rather than "ever employed" in a given work environment. The use of the usual panern may be more conservative in the detection of occupa- tional and industrial associations and is perhaps the more appropriate designation to use for a preliminary examination of the dati. As noted; the use of the usual oc- cupation and industry of employment did introduce some special constraints on the analysis of the female patterns in that the usual occupation and industry for over

98 /btrkfo K 8urffat. lindo Wfoms Pidcw. TTOmcs J. Moson .r d 60% of the caaes and contrc:; was "Housewife." We will employ a number of more specinc designations of occupational and industrial variablh in future aaalyus. Even witli these recognized limitations, the suggestion which dea:ly emerges frotn our data is that there may be a wider variety of workplace exposures as»ocated with substantial inaemenu in the risk of lung cancer than currently recogaised. In addition, use of tlie full work history, including dates will surely aid in refsning the preliminary assocsrions reported here. The relationship of lung cancer cell type with age at time of diagnosis warrants further scrutiny in that the highest odds ratios for the smoking variables were observed for the youngest age group (< 57 years at timeof'diagnosis): The lack ofa "passive smoking" effect when the confounding effect of smoking of individual' rtudy subjects is considered, is not consistent with early reports. Although subse- quent reports are also not consistent with regard to this asaociation, it may be that the study population available was not sufficiently large to detect a fairly low level: effect and that this association needs to be assessed in a considerably larger study population. Theae preliminary analyses demonstrate a strong and consistent smoking effect in males and females for all types of lung cancer. The risk differentials a»oaated witA cigarette smoking observed for adenocarcinorna and other lung cancer a1l rypes are striking and consistent with findings of others (11). In addition, they reemphasize earlier suggestions that perhaps specific environmental exposures are more strongly associated with specific types of lung cancer. In addition, these data suggest that perhaps lung cancer is more similar in males and females than previously regarded and that the observed difTerentiali in risk by sex are principally due to exposure differentials. Acknowledgments The authors thank Drs. Irene Easling and Keith Burau and their capable and dedicated staff for their invaluable assistance wiih the data collection and data managernent for this study. We also wish to acknowledge the valuable consultation and assistance of Dr. Robert Hardy (UTSPH), Dr. Reuel A.,Stallones (L'TSPH).. Dr. David T. Carr (M.D. Anderson Hospital and Tumor Institute), Dr. S. Donald Greenberg (Baylor College of Medicine), the staff of the Texas State Health Department Statewide Cancer Reporting Program and Bureau of Vital Statistics, and the American Lung Association, San Jacinto Chapter. And lastly, we wish to acknowledge the assistsnce of the many hospitals, physicians, agencies. and individuals without whom it would not have been possible for us to successfullyy complete this study. References 1'. Doii R, Pem R. ZAe cauas ef canear, quannrative erimatn of awidable rislu of cancer in the Urmed Stare todiy- Odordi Oxford University Prea., 1961. N i ~ WM W N Fs . ~