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APPENDIX E Additional Analyses The data compiled in connection with this study are numerous and varied; they hold more information than the design of this study could absorb. In this appendix, we first provide some greater detail of cohort characteristics (Tables E-1 to E-44. We then present the results of descriptive analyses and discuss their possible use in explaining relationships between participation and mortality. DETAIL BY COHORT We created four categories of paygrade to ensure groups of sufficient size for valid analysis. In Table E-1, we present the individual paygrade-level distri- bution by cohort. In the absence of military occupation information, the analysis attempted to explore whether the type of unit to which the participant and referent cohort individuals were assigned could be developed as an exposure proxy. Although this was not possible, the balance of unit types across the cohorts, shown in Ta- ble E-2, helps to ensure some control for hazardous exposures (other than radia- tion) that military personnel routinely face in their assignments. DETAIL BY SERVICE AND BY SERIES Later in this appendix, we present findings from exploratory analyses of se- ries- and service-specific hazard rations. Tables E-3 and E-4 display the distribu- tion of cohort member age and paygrade by selection series and branch of service. 183

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184 THE FIVE SERIES STUDY TABLE E-1. Cohort Member Characteristics: Paygrade ParticipantsReferentsTotal (n = 68,168)(n = 64,781)(n = 132,949) - Paygrade No. % No. % No. % E1 199 0.3 223 0.3 422 0.3 E2 6,471 9.5 6,034 9.3 12,505 9.4 E3 18,397 27.0 18,504 28.6 36,901 27.8 E4 11,976 17.6 12,015 18.6 23,991 18.0 E5 8,165 12.0 7,785 12.0 15,950 12.0 E6 4,833 7.1 4,647 7.2 9,480 7.1 E7 3,381 5.0 3,298 5.1 6,679 5.0 E8 6 0.0 1 0.0 7 0.0 E9 3 0.0 0 3 0.0 W1 240 0.4 206 0.3 446 0.3 W2 268 0.4 172 0.3 440 0.3 W3 41 0.1 40 0.1 81 0.1 W4 22 0.0 1 1 0.0 33 0.0 01 1,417 2.1 1,551 2.4 2,968 2.2 02 2,490 3.7 2,469 3.8 4,959 3.7 03 3,378 5.0 3,612 5.6 6,990 5.3 04 2,612 3.8 2,161 3.3 4,773 3.6 O5 2,187 3.2 1,290 2.0 3,477 2.6 06 1,276 1.9 688 1.1 1,964 1.5 07 162 0.2 37 0.1 199 0.1 08 148 0.2 20 0.0 168 0.1 O9 13 0.0 3 0.0 16 0.0 010 10 0.0 2 0.0 12 0.0 Missing 473 0.7 12 0.0 485 0.4 SERIES-SPECIFIC ASSOCIATIONS We display the data for all three endpoints separately by test series, by service branch, and by paygrade. For leukemia only, for which our study results were most interesting, we did a formal analysis of the heterogeneity of risks among test series. We fit a baseline model including a variable that represented the number of the five series in which an individual participated: 0 (for refer

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APPENDIXE 185 ents), and 1 to 5 for participants. We then fit a model with five dummy vari- ables, one variable for participation (yes or no) in each of the series. The differ- ence in fit (assessed by log likelihoods) between these two nested models repre- sents a formal test of the heterogeneity in leukemia risk between series. After adjusting for the number of non-five series tests, the difference in fit between these two models was 7.19, distributed as a x2 with 4 degrees of freedom. The associated probability is .13, indicating a lack of significant difference in leuke- mia risk among the five test series. Notwithstanding this lack of a statistically significant difference in leu- kemia risk among the five series, we decided to undertake further investiga- tions to identify subgroups with high leukemia risk. Part of the reason for this decision was to investigate further the significant excess risk among land se- ries participants (see below). However, we must acknowledge that the identifi- cation of high-risk subgroups is a pursuit fraught with difficulty; because there is no clear statistical evidence of differences, one may well be studying only statistical noise (i.e., expected random variation). However, it should also be noted that formal statistical tests of heterogeneity tend to have little statistical power. Table E-5 shows standardized mortality ratios (SMRs) and hazard ratios for the three primary mortality endpoints (all cause, all malignancies, and leuke- mia ~ by test series. SMR ratios are significantly less than 1.0 for all-cause mortality in series UPSHOT-KNOTHOLE and PLUMBBOB. The correspond- ing relative hazard for UPSHOT-KNOTHOLE is significantly less than 1.0, whereas the one for PLUMBBOB is not. In test series REDWING, all-cause and all-malignancy hazard ratios are significantly greater than 1.0. Although none of the SMR ratios or relative hazards for leukemia is sig- nificantly different from 1.0, the values are highest for series UPSHOT- KNOTHOLE, CASTLE, and PLUMBBOB. The SMR ratio for leukemia for the GREENHOUSE series is low, partly because the SMR for participants is low, but mostly because the SMR for referents is high, relative to all of the other series. Table E-6 shows similar data by service branch. Other than all-cause mor- tality among Air Force and Army servicemen (which is significantly lower among participants), no other SMR ratios are significantly different from 1.0. Marines show the highest SMR ratios for all three mortality endpoints, com- pared to other service branches, and it appears that these ratios are elevated be- cause participant SMRs are high, rather than referent SMRs being low. ICD-9 codes 204 through 208 apply to types of leukemia. In these analyses, based on current understanding of leukemia radiogencity, we exclude chronic lymphoid leuke- mia (ICD-9 code 204.1) from the grouping identified as leukemia.

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186 THE FIVE SERIES STUDY TABLE E-2. Cohort Member Characteristics: Type of Military Unit Participants (n = 68,168) Unit Category No. % ADMIN AIRDEF AIRDEVCEN AIRDIV ANTITANK ARMOR ARTILLERY AVIATION BASE BATTALION BOMB CAMP/STA CARGO CARRIER CENTER COMBAT COMMAND COMPANY COMSTAF CONTROL DESTROYR DETACHMT ENGINEER ESCORT FIGHTER FORT HELO HQTRS INFANTRY LAB 4,948 7.3 4,202 78 49 47 0.1 0.1 0.1 180 256 45 0 3 Referents (n = 64,781) No. % 6.5 0.3 0.4 0.1 0.0 1.2 5.4 4.8 3.6 0.2 1.2 0.0 1.2 4.6 0.2 3.8 2.1 0.4 3.0 1.3 3.7 943 3,646 2,5g2 4,817 125 559 15 853 1,814 141 2,568 1,199 287 2,317 323 2,432 8 1,340 664 370 26 486 890 1.4 5.4 3.8 47.1 0.2 0.8 0.0 1.3 2.7 0.2 3.8 1.8 0.4 3.4 0.5 3.6 0.0 2.0 1,374 1.0 0.5 0.0 0.7 1.3 7.8 94 0.1 766 3,513 3,082 2,307 111 767 795 2,948 112 2,439 1,362 259 1,929 825 2,397 7 537 307 o 245 837 5,582 76 Total (n= 132,949) No. % 9,150 258 305 92 3 1,709 7,159 5,674 7,124 236 1,326 17 1,648 4,762 253 5,007 2,561 546 4,246 1,148 4,829 0.0 15 2.1 2,714 0.8 1,201 677 26 731 1,727 10,904 170 6.9 0.2 0.2 0.1 0.0 1.3 5.4 4.3 5.4 0.2 1.0 0.0 1.2 3.6 0.2 3.8 1.9 0.4 3.2 0.9 3.6 0.0 2.0 0.9 0.5 0.0 0.6 1.3 8.2 0.1

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APPENDIX E TABLE E-2. Continued 187 Participants (in = 68,168) Unit Category No. % LCRAFT MAINT MAPCHART MATERIEL MEDICAL MISC OPERATION ORDNANCE REPAIR SALVAGE SERVICE SIGNAL SQUADRON STORESHIP SUBMARINE TACTICAL TANKERS TECHNICAL TENDERS TEST TRAINING TRANSPORT TUGS UNKNOWN WEATHER WING Referents (n = 64,781) No. % Total (in= 132,949) No. % 1,237 51 o 319 939 181 241 75 55 445 4,634 2,968 808 236 226 3,229 3,155 4,358 636 246 2,866 879 765 663 o 0.5 1.4 0.3 0.4 0.1 0.1 0.7 6.8 4.4 0.0 1.2 0.4 0.3 4.7 4.6 6.4 0.9 0.4 4.2 1.3 1.1 1.0 1.8 1,209 199 21 315 1,240 8 85 66 142 258 3,882 2,794 167 843 91 449 2,956 2,155 4,421 198 389 3,435 555 893 654 91 1.9 0.3 0.0 0.5 1.9 0.0 0.1 0.1 0.2 0.4 6.0 4.3 0.3 1.3 0.1 0.7 4.6 3.3 6.8 0.3 0.6 0.9 1.4 1.0 0.1 2,446 250 21 634 2,179 189 326 141 197 703 8,516 5,762 170 1,651 327 675 6,185 5,310 8,779 834 635 6,301 1,434 1,658 1,317 91 1.8 0.2 0.0 0.5 1.6 0.1 0.3 0.1 0.2 0.5 6.4 4.3 0.1 1.2 0.3 0.5 4.7 4.0 6.6 0.6 0.5 4.7 1.1 1.3 1.0 0.1

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194 THE FIVE SERIES STUDY Table E-7 shows data by paygrade. Except for a significantly low SMR ratio for all-cause mortality among officers, none of the SMR ratios differs from 1.0. We also see that officers, whether participants or referents, have lower SMRs than enlisted men, a finding to be expected, given the known effects of rank on mortal- ity (Seltzer and Jablon, 1977~. Subjects with unknown paygrade appear anomalous in that the SMRs of participants resemble those of officers, whereas the SMRs of referents resemble those of enlisted men. Regardless, the number of subjects with unknown paygrade is small (469 participants and 12 referents). Investigating Leukemia Risk Among Single Series Participants We thus began our investigation of subgroup risks by looking further at differences among the test series. Our first analysis of differences among series (Table E-5) was hampered by the fact that although the first of the five series at which a participant was present defines his "official" test series, in actuality participants could have been present at more than one of the five or indeed at other tests that were not part of the five series. Table E-8 shows participation status by assigned series. Participants are divided into two mutually exclusive participation categories: participation at assigned series or post-series only and all other (i.e., multiple series) participa- tion. The two land series, UPSHOT-KNOTHOLE and PLUMBBOB, are char- acterized by their relatively high percentage of participants who were only at their assigned series or post-series (i.e., relatively little multiple series participa- tion). On the other hand, GREENHOUSE and REDWING have the highest multiple participation rates, with roughly one-quarter of their participants having been present at other than their assigned series or post-series. In an attempt to get sharper estimates of leukemia and cancer mortality risk across series, we took the additional step of confining the analysis to individuals who participated only in their assigned series and at no other series. Limiting the analysis to participants who were at only one of the five series has the advantage of permitting an unconfounded comparison of mortality risks across test series, although the number of participants is reduced by roughly 15 percent, from 68,208 to 57,532. Table E-9 shows that among single series participants, the risk of leukemia mortality is elevated 25 percent or more among participants of all but two test series, GREENHOUSE and REDWING. Compared to all partici- pants, single series participants in UPSHOT-KNOTHOLE and CASTLE had lower leukemia risks, while there was little difference for PLUMBBOB (which had the highest proportion of single series participants).

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196 THE FIVE SERIES STUDY TABLE E-8. Number of Participants and Percentage by Assigned Series and Type of Participation Type of Participation At Series or Post- Series Only Remainder Total Assigned Series No. % No. % No. % GREENHOUSE 7,134 74.92,394 25.1 9,528 100 UPSHOT-KNOTHOLE 16,632 90.01,841 10.0 18,473 100 CASTLE 12,989 82.82,696 17.2 15,685 100 REDWING 10,093 78.12,830 21.9 12,923 100 PLUMBBOB 10,684 92.4875 7.6 11,559 100 Total 57,532 84.410,636 15.6 68,168 100 That is, participation in more than one series.

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