The Pratt & Whitney Epidemiology Study Phase 2 Incidence of Central Nervous System (CNS) Neoplasms

1. The Pratt & Whitney Epidemiology Study Phase 2 Incidence of Central Nervous System (CNS) Neoplasms Presentation of Phase 2 Results June 2-3, 2010

2. Research Teams Univ. of Pittsburgh (Epidemiology) Gary Marsh, PhD Jeanine Buchanich, PhD Ada Youk , PhD Frank Lieberman, MD Mike Cunningham, MS Terri Washington Univ. of Illinois at Chicago (Exposure Assessment) Nurtan Esmen, PhD Steve Lacey, PhD Kathleen Kennedy, MS Roger Hancock, MCE

3. Two-Part Presentation Part 1: Overview of Phase 2 Findings (Gary Marsh) Part 2: Overview of Exposure Assessment (Nurtan Esmen) PW_Phase 2 - 3

4. Purpose of the Overall Study To investigate the earlier perception of an unusual occurrence of glioblastoma at the P&W North Haven facility

5. P&W Study Highlights Remains one of largest and most comprehensive occupational cohort studies ever done Phase 1 mortality study and Phase 2 CNS neoplasm incidence study complete and published Focus on malignant CNS neoplasms as registry data on benign neoplasms mostly not available before 2004 Final Phase 3 work needs to be done Potential not only to learn more about health in the P&W workplace but also about possible causes of brain cancer PW_Phase 2 - 5

6. What was different about Phase 2 and Phase 1 ? • Phase 2 evaluated the incidence or occurrence of new cases of CNS neoplasms - Phase 1 examined deaths from CNS neoplasms • The event date of interest in Phase 2 was cases’ date of diagnosis - Phase 1 used date of death • Phase 2 provided first opportunity to examine incidence risk for specific CNS histologies, including glioblastoma, the histology of the North Haven index cases that prompted the overall study • Phase 1 diagnostic specificity limited to “malignant brain cancer”

7. Very Large Incidence Study Population • 212,513 men and women who worked in 1 of 8 P&W sites during 1952–2001 and at risk of becoming a case during 1976-2004 • North Haven (NH), East Hartford, Middletown, Rocky Hill, Cheshire, Southington – Aircraft Rd, Southington – Newell St, Manchester Foundry • Incidence evaluated 1976-2004 for 21 histological categories based on CBTRUS codes • 722 total CNS neoplasm cases • 489 malignant (275 glioblastoma) • 233 benign

8. Data Analysis Strategy All workers at risk 1976 - 2001 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

9. Phase 2 Findings Accepted for Publication in Leading Peer-Reviewed JournalOnline version-June 7, 2010Print version-August 2010

10. Phase 2 – Results External Comparisons

11. Total Cohort Level Findings – All Malignant CNS Histology Categories • We found that during the 1976-2004 study period, the total study population was diagnosed with fewer than expected cases for nearly all malignant CNS neoplasm categories examined, including glioblastoma, based on external comparisons with US and CT.

12. No Statistically Significant Elevations in Total Cohort Incidence Rates, 1976-2004, Compared with US and CT 1.23 1.15 # = observed cases 1.10 1.06 21 26 9 27 8 6 15 7 20 275 63 427

13. Subgroup Level Findings – Glioblastoma – CT Comparisons • We found a not statistically significant overall 8% excess among “only NH” workers compared with deficits in the other plant groups • We found elevated SIRs in several subgroups of workers from the “only” and “partial” NH groups, but none was statistically significant and few consistent patterns emerged • Consistent patterns unique to N. Haven workers included elevated SIRs for salaried workers and workers at risk of becoming a case in the oldest age group and latest time period

14. Glioblastoma Incidence Slightly Elevated but Not Statistically Significant in “Only NH” Group 179 35 43 18

15. Glioblastoma Incidence Most Elevated but Not Statistically Significant in Salaried “Only” & “Partial” NH Groups SIR = 2.17 # = observed cases SIR= 1.50 SIR= 1.09 SIR= 1.03 5 12 39 16 37 6 124 17 1 0 16 2

16. Phase 2 – Results Internal Comparisons

17. Findings for Glioblastoma - Internal Comparisons • For All Workers combined, none of the study factors considered was a statistically significant predictor of risk and none of the factor subcategory-specific RRs was statistically significant • For “Ever NH” workers (Only+Partial), only payroll type was a statistically significant predictor of risk due to statistically significant RR=2.04 for salary vs. (hourly + mixed) workers • For “Ever NH” workers, we found little or no evidence that risk was associated with other study factors including duration of work and time since first work

18. For All Workers, Glioblastoma Risk Higher in Only and Partial N. Haven Compared with Never N. Haven RR= 1.29 RR= 1.13 SIR= 1.08 RR= 1.00 43 cases 18 cases 35 cases 179 cases

19. For “Ever NH” Workers (Only + Partial), Only Payroll Type Was Statistically Significant Predictor of Glioblastoma Risk RR=2.04 p < .05 SIR= 1.65 RR= 1.00 44 cases 17 cases

20. For “Ever NH” Workers, Little Evidence That Glioblastoma Risk Associated with Duration of Work RRs adjusted for payroll type SIR= 1.33 RR= 1.32 RR= 1.07 RR= 1.00 23 cases 15 cases 11 cases 12 cases

21. For “Ever NH” Workers, No Evidence That Glioblastoma Risk Associated with Time Since First Worked RRs adjusted for payroll type SIR= 1.17 RR= 1.00 16 cases 27 cases 13 cases 5 cases

22. Phase 2 – Results Other Findings PW_Phase 1 - 22

23. Detailed Evaluation of Other Malignant CNS Neoplasm Histologies • Evaluated 3 categories with 25+ total cases (astrocytoma-NOS, glioma-malignant and lymphoma) using external and internal comparisons • Limited to total incidence subcohort due to small numbers of plant group-specific cases • Revealed no consistent evidence of trends or patterns in SIRs or RRs suggestive of an association related to P&W employment

24. How did the main results of Phase 1 and Phase 2 compare? • Overall findings for cancer incidence consistent with overall findings for CNS neoplasm mortality during same 1976-2004 study period • Reduced SMRs for “all malignant CNS neoplasms” • Reduced SMRs for “malignant brain neoplasms” • Patterns of study factor-specific glioblastoma risks similar to those observed for “malignant brain cancer” in Phase 1 mortality study

25. Overall Findings Consistent for Similar CNS Neoplasm Categories in Phase 1 and Phase 2 Phase 1 Mortality Phase 2 Incidence SMR= .94 SIR= .76 SIR= .77 SMR= .95 SMR= .87 275 427 381 462 398

26. Example: Phase 1 Findings for Malignant Brain Cancer by Payroll Type Consistent with Phase 2 Findings for Glioblastoma (1976-2004) Phase 2 – Glioblastoma Incidence Phase 1 – Malignant Brain Cancer Mortality

27. Conclusions from Phase 2 • Total cohort incidence rates for malignant CNS neoplasms, including glioblastoma, were not elevated compared to US and CT general populations • Glioblastoma excesses unique to 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 • Glioblastoma excesses in NH will be further evaluated in Phase 3 of the study

28. P&W Epidemiology StudyUpcoming Work

29. What Comes Next ? Phase 3 • Completion of exposure assessment (Dr. Esmen to discuss) • Re-evaluate total and cause-specific mortality in relation to detailed work history and workplace exposure information • Re-evaluate incidence of malignant CNS neoplasms in relation to detailed work history and workplace exposure information

30. Estimated Timeline for Phase 3

31. 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 and Aerospace Workers (IAMAW) • The Communications Facilitation Workgroup

32. Questions?

33. Part 2Exposure Assessment PW_Phase 1 - 33

34. END PW_Phase 2 - 34