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signature o r r31r.. with reply. directly lo OCli. letter. Regarding Analysis Of Hatiford-1---- portion a l- ~ 140rtality Data, Enclosures: As Stated (3) Copies CODE: 1. Appropriate Hai idl ii lg 2. Info. 3.Admln. Sig.
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Analysis o f Hanford Proportional Mortality Data, Adjusted for Age and Year of Death The analysis sumarized i n the attached tables was done t o investigate the suggestion that some of the results reported by Flancuso, Stewart, and Kneale may be explainable as artifacts of their analysis. The approach has been ' to adjust for certain possible confoundings, viz., association of cumulative dose with age of death and year o f death, and possible selection factors between exposed and non-exposed workers; t o compute test statistics that do not assume a symmetric distribution for dose; and t o analyze the death certificate data provided by ORNL insufficient detail that some judgment can be made a s t o the extent of the bias introduced by a proportional mortality analysis, and as to whether the reported radiation effects could be extreme results to be expected by chance alone from a large number of The basic statistical procedure has been a contingency table method, adjusted for age a t death ( 2 4 9 , 50-64, 65+) and year of death (1943-60, 1961-67, and 1968-73). A t each level of these factors(e.g., 549 and 1943-60, -<49 and.1961-67, e t c . ) 2 x k ( k = 6 and 11) contingency tables were tabulated, rows corresponding t o death from a.specified disease or from other causes and columns t o non-exposed andto dose intervals within the exposed class. - Expected cell frequencies, variances, and covariances were cornnputed from row and column sums, and then summed over tables t o provide details of the nullhypothesis distribution of the summary tables.' The main statistical results are the p-values for the exposed vs. non-exposed comparison and for the test of linear trend with dose adjusted
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for exposure; a value near one of the latter indicatqs a positive association of the corresponding cause of death w i t h 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 of a dose response, suggest selection of the exposed or non-exposed popul'ation f o r reasons 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 at a included as a check on the possible effects of skewness of the dose distribution. The trend statistics for the cube root of dose were The finer dose intervals in the l l - interval tables provide greater power against increasing trends; the 6-interval tables provide a check against.numerica1 or distribution al instability of the test statistics. Analyses were performed for cumulative dose a t death, andat3,5,10, 15, and 20 years prior t o death. Cancers were treated separately for each 3-digit ICD code, and i n broader groups. Non-cancers were treated i n broad groups, except for chronic bronchitis and emphysema, which were treated 4Several causes of death were present much more, o r much less,in the exposed than in the non-exposed, indicating that the groups probably were selected on some basis related t o health. and multiple myeloma, were significantly related t o dose among males. non-cancer, chronic MI, consistently decreased w i t h increasing dose. Since Two cancers, pancreatic cancer the results for pancreatic cancer and multiple myeloma are based on relatively few cases, i t seems unlikely that these results could be ascribed toa defect
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o f the proportional mortality approach; selection of the exposed population, even differential ly by dose, could not be expected t o create a n apparent dose relationship for these diseases alone. However, a closer examination of each of the individual diagnoses would be i n order, since ooly a few misdiagnoses could have created the effects. Pancreatic cancer, i n part j cula r, has a relatively low percentage of his to logically proven cases compared with other cancer sites, and therefore may be unusually subject t o misdiagnosis on death certificates. Cancers of the lung, brain, and female breast appeared t o be related t o dose i n unadjusted contingency table analyses, but these apparent relationships did not survive adjustnient for age and year of death. [The possibility that the results for pancreatic cancer and mu1 tiple 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 out. This seems less likely for multiple myeloma than for pancreatic cancer, however, since multiple myeloma isa very rare disease and the dose distribution of the cases other cancers, have been reported among U.S. and British radiologists. the other hand, the evidence fora dose response for these two diseases Excess risks of multiple myeloma and pancreatic cancer, among aniong Japanese A-bomb survivors i s very weak. evidence fora dose effect among Hanford workers should involve these two diseases and not leukemia o r malignant lymphomas other than mu1 tiple I t is somewhat surprising that
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