Analysis to Hanford Proportional Mortality Data, Adjusted for Age and Year of Death

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Analysis o f Hanford Proportional I4ortal ity Data, Adjusted for Age and Year of Death 705402 The analysis sun a rize d in the attached tables was done to investigate the suggestion that some of the results reported by Mancuso, Stewart, and Kneale may be explain able as artifacts of their analysis. The approach has been to adjust for certain possible confoundings, viz., as s mi ation of cumulative dose with age of death and year of death, and possible se!ection factors between exposed and non-exposed workers; t o compute test stzt isti cs tnat do not assume as y metric distribution for dose; and to analyze the death certificate data provided by OR?fL insufficient detail that soxe jud gm nt can be made as to the extent of the bias intro dx ed by a prc;ortional mort zl it y analysis, and as t o whether the reported radiation effects cx1d be extreme results to be expected by chance alone from a large nl;mber of The basic statistical procedure has been a contingency table method, adjusted for age at death(549, 50-64, 65+) and year of death (1943-60, A t each level of these factors(e.g - ,549 and 1943-60, rows corresponding to death from a specified disease or from other causes and columns t o non-exposed and t o dose intervals within the exposed class. - Expected cell frequencies,variances, and covariances were cmputed fx m rox and column sums, and then s mz dover tables to pr ~ vid ed e tails of the null - hypothesis distribution of the su mary tables. .-. non-exposed cornpzrjson an a for the test of l ' nes r trend with dose aci j z std

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for exposure; a value near on2 of the latter indicates a positive association o f the corresponding cause of death with cumulative dose, a value near zero indicates a negative association. Extreme p-values f o r the exposed - non-exposed comparison, i n the absence o f a dose response, . suggest selection of the exposed o r non-exposed popul'ation for reasons related t o health. An extreme p-value for linear trend unadjusted for exposure, with more moderate p-values for the main two statistics,might suggest'a true dose response, especially i f the adjusted trend statistic is ata "suggesti-vel' level. The trend statistics for the cube root of dose were included as a check on the possible effects of skewness o f the dose distribution. The finer dose intervals i n the 11-interval tables provide greater power against increasing trends; the 6-interval tables provide a check against,numerical or distributional instability of the test statistics. Analyses were performed for cumulative dose a t death, and a t 3 , 5 , 10, 15, and 20 years prior t o death. 3 - digit ICD code, and i n broader groups. groups, except f o r chronic bronchitis and emphysema, which were treated Several causes o f death were present much more, or much less,in the Cancers were treated separately f o r each Nan-cancers were treated in broad exposed than in the non-exposed, indicating that the groups probably were selected on sone basis related to health. and multiple my210na, ~ e r 2s ign if i cant ly related t o do52 arrong ma'es. Two cancers, pancreatic cancer non-cancer, chronic MI, consistently decreased w i t h increasing dose. Since the results for pancreatic cancer and multiple myelcma are bzsed cz t?!?tively few cases, i t seem unls kely that these results could h asc+bed toE defect

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of the proportional niortal it y approach; selection o f the exposed population, even differential ly by dose, could not be expected t o create an apparent dose relationship for these diseases aloae. Hcwever, a closer examination o f each of the individual diagnoses would be i n order, since only a few misdiagnoses could have created the effects. Pancreatic cancer, i n ’ part j cula r, has a relatively low percentage of histologically proven cases compared with other cancer sites, and therefore may be unusually subject t o misdiagnosis on death certificates. Cancers of the lung, brzin, and female breast appeared t o be related t o dose in unadjusted contingency table analyses, but these apparent relationships did not survive adjustment for age and y e ~ rof death. [The possibility that the results for pancreatic cancer and multiple myeloma are statistical flukes, which might be expected t o be obtained i n an analysis of many different causes of death, cannot be ruled cut.This seems ~..--less likely for multiple myeloma than for pancreatic cancer, however, since multiple myeloma isa very rare disease and the dose dist rih tion of the cases is- ext rem. Excess risks of multiple myeloxa and pancreatfc cancer, among other can css, have been reported among U.S. and British rad k logi sts. On the other hand, the evidence for a dose response for these b o diseases among Japanese A-bomb survivors i s very weak-1 Itis somewhat surprising that evidence fora dose effect among Hanford workers should in ml ve these two diseases a n d not leukemia or malignant lymphomas other thm multiple