1. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 1 Presentation of Phase 1 Results Presentation of Phase 1 Results September 18, 2008 The Pratt & Whitney Epidemiology Study Phase 1 (Cohort Mortality)

2. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 2 Purpose of the Study To investigate the earlier perception of an unusual occurrence of glioblastoma at the P&W North Haven facility

3. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 3 P&W Study Highlights One of the largest and most comprehensive occupational cohort studies ever done Phase 1 mortality study is complete and published. Much more work needs to be done (Phases 2 and 3) Potential not only to learn more about health in the P&W workplace but also about possible causes of brain cancer

4. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 4 P&W Cohort Mortality Study One of the Largest and Most Comprehensive Occupational Cohort Studies

5. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 5 What information was used? The researchers looked at: – –Plant records of when and where people worked and their age, race and gender – –National and state records If workers were living or deceased Specific cause of death for deceased workers Focus on malignant brain cancer and benign brain tumors The researchers compared: – –Numbers of deaths among workers to the number expected in the general populations of the US and CT

6. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 6 Very Large Cohort of Workers 223,894 men and women that worked in one of 8 P&W sites during 1952 - 2001 –North Haven (NH), East Hartford, Middletown, Rocky Hill, Cheshire, Southington – Aircraft Rd, Southington – Newell St, Manchester Foundry –Includes work at plants in Maine, Florida & Georgia for transferred employees –26,801 (12%) workers at NH only; 11,898 (5%) partial NH Mortality evaluated 1952-2004 for all causes and CNS cancer, 1976-2004 focus for CNS cancer –68,701 total deaths identified

7. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 7 Data Analysis Strategy All workers, 1952-2004 Work-related factors Plant group, pay type Year of hire, age at hire Duration of work Time since first work Non work-related factors Race, sex Age group, time period North Haven workers by study factors Combined Data Study factors Subgroups by study factors

8. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 8 Phase 1 Findings Accepted for Publication in Leading Peer-Reviewed Journal (Oct 2008)

9. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 9 Phase 1 - Results Total & Cause-Specific Mortality (Excluding CNS Neoplasms)

10. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 10 Total Cohort Level Findings Total cohort mortality rates, 1952-2004, for all causes combined, all cancers combined and most other cause of death categories examined were not elevated compared to US and CT populations Total cohort mortality rates, 1952-2004, for all causes combined, all cancers combined and most other cause of death categories examined were not elevated compared to US and CT populations

11. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 11 Total Cohort Mortality Rates, 1952-2004, Not Elevated Compared to US and CT Populations

12. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 12 Subgroup Level Findings Only 3 of 63 disease categories revealed a greater than 25% statistically significant excess in deaths Only 3 of 63 disease categories revealed a greater than 25% statistically significant excess in deaths –Kidney cancer (30%) & non-malignant respiratory disease (27%) in the only North Haven plant group –Bronchitis in hourly workers (28%)

13. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 13 Only Two Diseases Revealed a Greater than 25% Statistically Significant Excess by Plant Group

14. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 14 Only One Disease Revealed a Greater than 25% Statistically Significant Excess by Payroll Type

15. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 15 What do the results mean? No evidence of elevated mortality risks for: –All causes combined –All cancers combined –Most of the cause of death categories examined Not unusual in studies of workers: –Workers are generally healthier than people in the general population –Improved access to health care –Improved quality of life

16. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 16 What do the results mean (contd)? Findings for kidney cancer, bronchitis and non-malignant respiratory disease suggest that the excesses may be due to non-work factors or to work outside of P&W: –Mainly among short-term, hourly workers –No associations with available work-related factors, such as duration of employment at P&W These excesses will be evaluated further in Phases 2 and 3 of the study

17. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 17 Phase 1- Results Mortality from CNS Neoplasms

18. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 18 Total Cohort Level Findings Total cohort mortality rates, 1952-2004, for all CNS neoplasms not elevated compared to US and CT populations Total cohort mortality rates, 1952-2004, for all CNS neoplasms not elevated compared to US and CT populations –Same finding for malignant, benign and unspecified CNS neoplasms Total cohort mortality rates, 1976-2004, for all brain neoplasms not elevated compared to US and CT populations –Same finding for malignant, benign and unspecified brain neoplasms

19. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 19 Total Cohort Mortality Rates for CNS Neoplasms Not Elevated Compared to US and CT Populations 606 462 23 121

20. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 20 Subgroup Level Findings Not statistically significant excesses in deaths from all malignant brain neoplasms among NH workers –11% excess among only NH workers –4% excess among partial NH workers Malignant brain neoplasms in combined NH groups –Not statistically significant higher risks in salaried workers, older hires and the most recent time period –No association with duration of employment or time since first employment

21. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 21 Malignant Brain Rates Slightly Elevated in Ever (Only + Partial) NH Group 492425157

22. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 22 Malignant Brain Rates Elevated for Salary Workers in Ever NH Group 51255274310262154 SMR= 1.36 # = observed deaths SMR= 1.08 1811 SMR = 1.91

23. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 23 Malignant Brain Rates Elevated for 1995-2004 Time Period in Ever NH Group 845313139261110018 SMR= 1.06 SMR = 1.50 # = observed deaths SMR= 1.14 9828

24. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 24 Malignant Brain Rates in Ever North Haven Group Not Related to Duration of Time Worked at PW

25. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 25 What do the results mean? Total cohort mortality rates for CNS neoplasms and brain neoplasms (malignant, benign or unspecified) not elevated compared to US and CT general populations Malignant brain excesses in certain subgroups of workers from NH may be due to work outside of P&W, non-work factors or workplace factors unique to NH not measured in the current phase of the study These excesses will be further evaluated in Phases 2 and 3 of the study

26. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 26 P&W Epidemiology Study Upcoming Work

27. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 27 What comes next? Phase 2 –Examine the relationship between basic work history factors and brain cancer incidence –Will enable evaluation of specific types of brain cancer, such as glioblastoma

28. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 28 What comes next (contd) ? Phase 3 –Re-evaluate total and cause-specific mortality in relation to detailed work history and workplace exposure information –Re-evaluate brain cancer incidence in relation to detailed work history and workplace exposure information –Compare work and non-work related factors in the brain cancer cases and their matched controls –Evaluate brain tissue samples from some workers with brain cancer to see if patterns of genetic change are the same as in brain cancer cases from the general population

29. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 29 Acknowledgments We gratefully acknowledge the support, cooperation and assistance of the following groups without whose help this study would not be possible: –The CT Dept. of Public Health –The Scientific Advisory Council –P&W HR and EHS personnel –The International Association of Machinists (IAM) –The Communications Facilitation Workgroup

30. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 30 Research Teams Research Teams Univ. of Pittsburgh (Epidemiology) Gary Marsh, PhD Jeanine Buchanich, PhD Ada Youk, PhD Frank Lieberman, MD Mike Cunningham, MS Zb Bornemann, MS Univ. of Illinois at Chicago (Exposure Assessment) Nurtan Esmen, PhD Steve Lacey, PhD Kathleen Kennedy, MS Roger Hancock, MCE

31. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 31 Questions?

32. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 32 P&W Phase 1 Summary Very large and comprehensive study Phase 1 mortality study complete and published, Phases 2 & 3 analyses ongoing Study will inform workers, companies and brain cancer research community about occupational health risks for brain cancer Continue to encourage and promote participation in the case-control study

33. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 33 Contact Information Gary M. Marsh, Ph.D., Principal Investigator for the University of Pittsburgh Epidemiology component can be reached at gmarsh@cobe.pitt.edu gmarsh@cobe.pitt.edu Nurtan A. Esmen, Ph.D., Principal Investigator for the University of Illinois at Chicago Exposure Reconstruction component can be reached at nesmen@uic.edu nesmen@uic.edu Frank S. Lieberman, M.D., Co-Investigator and neuro-oncologist can be reached at liebermanf@msx.upmc.edu liebermanf@msx.upmc.edu The researchers can also be reached: –by calling toll-free 1-866-621-1172 –from their website (http://cobe.biostat.pitt.edu/) http://cobe.biostat.pitt.edu/ Information and updates on the study are also available on the CTDPH website: –http://www.ct.gov/dph/cwp/view.asp?a=3140&q=387474

34. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 34 END