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ST000I 788 ABSTRACT DETERMINANTS OF LUNG CANCER AMONG CHEMICAL WORKERS fay Gregory G. Bond Chairman: Ian T. T. Higgins Prior study of a sample of employees from Dow Chemical U.S.A., Texas Division had suggested lung cancer rates were excessive. This dissertation describes the results of two epidemiologic studies which were conducted to determine if the excess persisted upon study of all employees, and if the risk of lung cancer was associated with one or more exposures at the facility. A historical cohort mortality study was conducted of the 19,608 males with one or more years of employment accumulated between 1940 and 1981. Vital status was ascertained through 1980 for 97.3 percent of the subjects and death certificates were obtained for 96.4 percent of the 3,444 decedents. Lung cancer occurred significantly more often than expected based on rates for the U.S. (SMR = 125) and Texas (SMR = 118), but occurred as often as expected based on rates for the five local counties (SMR = 99). Mortality from 56 other causes of death was also assessed. The influence of a number of employment characteristics, including educational level and job category, was explored using the MantelHaenszel method as adapted for a cohort study. 407462 A nested case-control study was dene cf the 308 lung cancer deaths. Two control groups, one of which was a decedent series, were individually matched to the cases one-for-one. Interviews were conducted with subjects or their next-of-kin to collect information on smoking ana other potential confounaers. Those data were conjoined with employee wortc history records and industrial hygiene data to form the basis cf the analysis. Conditional logistic regression and stratification techniques were employed to examine for effect modification and to control confounding. Not surprisingly, cigarette smoking was the most important determinant of lung cancer risk. Being of lower social class and consuming foods rich in Vitamin A less often were weaker determinants. Statistically significant, positive and negative associations were found for assignment to several work areas within tne facility and with presumptive exposure to several chemical and physical agents encountered in those work areas. The lack of strength and consistency of the associations precluded incriminating any particular workplace exposure as having been causally-related to lung cancer. 407463 ST000I 789 DETERMINANTS OF LUNG CANCER AMONG CHEMICAL WORKERS by Gregory G. Bond A di ssertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Epidemiologic Science) in The University of Michigan 1985 ST000I 790 Doctoral Committee: Professor Ian T. Higgins, Chairman Professor Richard G. Cornell Professor Millicent W. Higgins Assistant Professor Lawrence D. Whitehead 407464 TABLE OF CON., I ENTS DEDICATION ..................................................... ii ACKNOWLEDGEMENTS .................................................................................... Hi LIST OF TABLES ....................................................................................... ix LIST OF FIGURES ..................................................................................... xv LIST OF APPENDICES ................................................................................ xvi CHAPTER I. INTRODUCTION ........................................................................ 1 Background ............................................................................ Significance ........................................................................ Purpose .................................................................................. 1 6 6 II. LITERATURE REVIEW ............................................................... 9 Age, Ethnicity and Sex ..................................................... 10 Time Trends .......................................................................... 11 Geographical Variation ..................................................... 12 Urbanization and Air Pollution ...................................... 14 _ Social Class ........................................................................ 15 Religion ................................................................................ 16 Histopathology .................................................................... 16 Tobacco .................................................................................. 18 Radiation .............................................................................. 22 Asbestos ................................................................................ 23 Occupational Exposures ..................................................... 24 Nutrition .............................................................................. 33 Host Factors ........................................................................ 39 Summary .................................................................................. 41 III. MATERIALS AND METHODS ....................................................... 42 Historical Cohort Mortality Study ................................ 42 Description of the Facility .................................. 42 Cohort Definition and Identification ................. 44 vi ST000I 79 I 407465 TABLE OF. CONTENTS (continued) Verification of the Completeness of the Employee Census .................................................... Vital Status Follow-up .................................. Nosologic Coding of Death Certificates .............. Analysis Methods .................................................... External Comparisons ................................................ Internal Comparisons ................................................ 43 52 5456 58 61 Nested Case-Control Study ................................................ 63 Introduction ............................................................... Case Definition and Ascertainment ....................... Histopathological Verification of Diagnosis ... Control Groups Selection ........................................ Exposure Characterization ...................................... Dow Occupational Exposures .................................... Telephone Interviews ............................................. Data Preparation......................................................... Analysis ....................................................................... 63 63 64 68 71 74 79 85 87 IV. RESULTS ................................................................................... 92 Historical Cohort Mortality Study ................................. 92 Characteristics of the Study Cohort ................... 92 Vital and Employment Status .................................. 103 External Comparisons:U.S. Rates ............................ 107 External Comparisons: Texas and 5-County Area Rates ......................................................... 112 Internal Analysis ...................................................... 115 Age at Hire ................................................................. 117 Period of Hire ........................................................... 119 Interval Since Entry ................................................ 121 Duration of Employment ............................................ 123 Educational Level ...................................................... 125 Job Category ............................................................... 127 Employment Status ...................................................... 132 Simultaneous Control of Several Variables ........................................................... 134 Nested Case-Control Study ................................................ 141 Descriptive ................................................................. 141 Histopathology ........................................................... 143 Interview Results ...................................................... 148 Interview Validations ............................................ 155 vi i ST0001792 407466 TABLE OF CO &FE NTS {conti Univariate Analyses .................................................. 156 Cigarette Smoking ..................................................... 157 Residence History ..................................................... 174 Dietary Vitamin A ..................................................... 182 Employment and Exposures Outside of Dow .......................................................................... 186 Socioeconomic Level ................................................. 189 Work Area Comparisons .................................... 191 Chemical and Physical Agent Exposure Comparisons ......................................................... 201 Stratified Analyses ................................................ 227 Conditional Logistic Regression Analyses ................................................................. 225 V. DISCUSSION .......................................................................... 245 Historical CohortMortality Study ............................... 245 Nested Case-Control Study ............................................... 253 Summary ................................................................................ 272 APPENDICES ............................................................................................. 274 REFERENCES ............................................................................................. 327 vi i i 407467 ST000 I 793 LIST OF TABLES TABLE Page II. 1 III.I 111.2 111.3 111.4 111.5 111.6 111.7 111.8 111.9 111.10 IV.1 IV.2 IV.3 IV.4 Known or Suspect Occupational Carcinogens Present in the Texas Division Work Environment........................................................................... 34 Data Elements Recorded for Employee Census ................. 47 Results of Verification of Completeness of Employee Census ................................................................... 51 12-Point Hierarchical Algorithm Used to Verify Correct DeathCertificates ................................................ 55 Summary of Quality Assurance on Nosologic Ceding of Underlying Cause of Death by Revision and Error Type ............................................................................. 57 International Classification of Diseases Codes Used to Select Lung Cancer Cases ................................... 65 Exposure Variables ............................................................... 73 Computerized Work History as Provided to Industrial Hygienist for Chemical and Physical Agent Profile Development ................................................ 75 Advantages and Disadvantages of Work Area or Chemical and Physical Agent Profiles as Exposure Variables ............................ 76 Example of Chemical and Physical Agent Profile ......... 78 Description of Exposure Variables .......... 86 Distribution of Cohort Members by Ethnic Group .......... 93 Distribution of Cohort Members by Duration of Employment ............................................................................. 96 Distribution of Cohort Members by Job Category and Year of Entry .............................................................. 100 Distribution of Cohort Members by Job Category and Duration of Employment ............................................. 101 STOOOI79U ix 407468 TABLE LIST OF TABLES (continued) Page IV.54 IV.55 IV.55 IV.57 IV.58 Summary of Stratified Analyses - Two Variables Considered Simultaneously .............................................. 229 Model Fitting Statistics For Sulfur Dioxide Lung Cancer Association - Control Series 1 ............. 236 Model Fitting Statistics For Sulfur Dioxide Lung Cancer Association - Control Series 2 ............. 228 Model Fitting Statistics For Lung Cancer-Heat Association - Control Series 1 .................................... 241 Model Fitting Statistics For Lung Cancer-Heat Association - Control Series 2 .................................... 243 STOOOI 795 xi v 407469 LIST OF FIGURES FIGURE Page IV.1 IV.2 IV.3 IV.4 IV.5 IV.6 Distribution of Cohort Members by Age at Hire and Year of Hire .................................................. 95 Distribution of Cohort Members by Job Category and Education ............................................... 98 Summary of Follow-up Effort Fcr Present and Former Dow-Texas Division Emplovees (Vital Status as of12/31/80) ................................... 104 Lung Cancer Rate in the Cohort by Age and Year of Event ......................................................................... 116 Summary of Efforts to Gain Histopathological Diagnosesof Lung CancerPatients .............................. 147 Distribution of Lung Cancer Cases by County of Birth ............................................................................... 175 ST000I 796 xv 407470 LIST OF APPENDICES APPENDIX Page A Calculation of Region-Specific Mortality Rates .................................................................................... 274 B Brief Description of General Job Categories .......................................................................... 277 C Release of Medical Information Form, Letters to Hospitals andPathologists ........................................ 279 D Work Area Classifications .............................................. 284 E Living Subject and Next-of-Kin Questionnaire, Interview Instructions, Script for. Interview Validation and Letter toInterview Refusals .............. 286 F Validation of Dow Work Histories Obtained From Interviews ................................................................. 321 G Unmatched Analyses of Frequency of Consumption of 29 Food Items ......................................................... 328 ST000I 797 xvi 407471