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The Radiation Effects Research Foundation has recently implemented a new dosimetry system, DS02, to replace the previous system, DS86. This paper assesses the effect of the change on risk estimates for radiation-related solid cancer and leukemia mortality. The changes in dose estimates were smaller than many had anticipated, with the primary systematic change being an increase of about 10% in gamma-ray estimates for both cities. In particular, an anticipated large increase of the neutron component in Hiroshima for low-dose survivors did not materialize. However, DS02 improves on DS86 in many details, including the specifics of the radiation released by the bombs and the effects of shielding by structures and terrain. The data used here extend the last reported follow-up for solid cancers by 3 years, with a total of 10,085 deaths, and extends the follow-up for leukemia by 10 years, with a total of 296 deaths. For both solid cancer and leukemia, estimated age-time patterns and sex difference are virtually unchanged by the dosimetry revision. The estimates of solid-cancer radiation risk per sievert and the curvilinear dose response for leukemia are both decreased by about 8% by the dosimetry revision, due to the increase in the gamma-ray dose estimates. The apparent shape of the dose response is virtually unchanged by the dosimetry revision, but for solid cancers, the additional 3 years of follow-up has some effect. In particular, there is for the first time a statistically significant upward curvature for solid cancer on the restricted dose range 0-2 Sv. However, the low-dose slope of a linear-quadratic fit to that dose range should probably not be relied on for risk estimation, since that is substantially smaller than the linear slopes on ranges 0-1 Sv, 0-0.5 Sv, and 0- 0.25 Sv. Although it was anticipated that the new dosimetry system might reduce some apparent dose overestimates for Nagasaki factory workers, this did not materialize, and factory workers have significantly lower risk estimates. Whether or not one makes allowance for this, there is no statistically significant city difference in the estimated cancer risk.

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This study extends an earlier one by 4 years (1979-1982) and includes mortality data on 11,393 additional Nagasaki survivors. Significant dose responses are observed for leukemia, multiple myeloma, and cancers of the lung, female breast, stomach, colon, esophagus, and urinary tract. Due to diagnostic difficulties, results for liver and ovarian cancers, while suggestive of significant dose responses, do not provide convincing evidence for radiogenic effects. No significant dose responses are seen for cancers of the gallbladder, prostate, rectum, pancreas, or uterus, or for lymphoma. For solid tumors, largely due to sex-specific differences in the background rates, the relative risk of radiation-induced mortality is greater for women than for men. For nonleukemic cancers the relative risk seen in those who were young when exposed has decreased with time, while the smaller risks for those who were older at exposure have tended to increase. While the absolute excess risks of radiation-induced mortality due to nonleukemic cancer have increased with time for all age-at-exposure groups, both excess and relative risks of leukemia have generally decreased with time. For leukemia, the rate of decrease in risk and the initial level of risk are inversely related to age at exposure.

Purpose: Although NY-ESO-1 was isolated from an esophageal carcinoma patient, its expression in this type of cancer and its immunogenicity in esophageal cancer patientshave not yet been fully elucidated. We report here the frequency of NY-ESO-1 mRNA and protein expression in esophageal cancer and the presence of NY-ESO-1-specific immune response in patients.Experimental Design: One hundred twenty three esophageal squamous cell carcinoma specimens were analyzed for the expression of NY-ESO-1 mRNA by conventional and real-time reverse transcription-PCR and the expression of protein by immunohistochemistry and Western blot. Sera and peripheral blood lymphocytes from 51 patients were analyzed for the NY-ESO-1 antibody production by enzymelinked immunosorbent assay and NY-ESO-1 T cell response by enzyme-linked immunospot assay. Survival analyses were also performed.Results: NY-ESO-1 mRNA was expressed in 41 of 123 (33%) esophageal squamous cell carcinoma specimens, and its expression was found at higher frequency in well-differentiated and moderately differentiated type of cancer. No mRNA copy was detected in any of the adjacent normal tissues. Twenty-one of 24 (87.5%) NY-ESO-1 mRNA-positive tumors were stained positively by immunohistochemistry. Correlation between the level of NY-ESO-1 mRNA expression and the degree of immunohistochemistry positivity was observed. Antibody production was observed in 2 patients with tumors that showed protein expression. Furthermore, a CD8 T-cell response against NY-ESO-1 was observed in 1 of the 2 seropositive patients.Conclusions: The high expression frequency of NY-ESO-1 mRNA and protein indicates NY-ESO-1 as a feasible vaccine target in esophageal cancer.

As a result of the reassessment of the A-bomb dosimetry, new (DS86) doses were calculated in 1986. In this paper, site-specific estimates of cancer mortality in the years 1950-1985, based on these new doses, are compared with those using the T65DR doses. The subjects of the study are 75,991 members of the Life Span Study sample for whom DS86 doses have been calculated. This reevaluation of the exposures does not change the list of radiation-related cancers. Most differences in dose response between Hiroshima and Nagasaki are no longer significant with the DS86 doses. The dose-response curve is closer to linear with the DS86 than the T65DR doses even for leukemia in the entire dose range, though, statistically, many other models cannot be excluded. However, in the low-dose range, the risk of leukemia remains nonlinear. Assuming a linear model at an RBE of 1, and using organ-absorbed doses, the risk coefficients derived from the two dosimetries are very similar, whereas those based on shielded kerma are about 40% higher with the new dosimetry. If RBE values larger than 1 are assumed, the disparity between the two dosimetries increases because the neutron dose is much greater in the T65DR. At an RBE of 10, for the five specific cancers, i.e., female breast, colon, leukemia, lung, and stomach, the increase in excess number of deaths per 10(4) PYSv under the DS86 varies from 12% (colon) to 133% (female breast). The magnitude of the effects of such modifiers of radiation-induced cancer as age at time of bomb and sex do not differ between the two dose systems.

A number of prospective studies in the USA and Europe have demonstrated that quantitative ultrasound (QUS) measurements predict fracture risk. To our knowledge, there has been no such study in a Japanese population, and very few studies have measured the prognostic value of QUS measurements among men, even in the USA and Europe. We performed a three-center prospective study to investigate the relationship between baseline heel QUS measurements and non-spine fracture risk. There were 4,028 subjects (1,004 men and 3,024 women), 67.5+/-8.9 years [mean +/- standard deviation (SD)] of age), who underwent heel QUS (Achilles device) at three centers between 1993 and 2000. In 2002, the subjects were mailed a standardized questionnaire that asked about their history of fracture. The mean follow-up period was approximately 5 years. The Achilles measured speed of sound (SOS) and broadband ultrasound attenuation (BUA). We used Cox regression analysis to determine the hazard ratio (HR), using weighted coefficients. SOS, BUA, and stiffness index (SI) predicted self-reported hip, wrist, and total non-spine fractures. After we had adjusted for age, gender, and weight, the HRs of total non-spine fracture were 1.54 [95% confidence interval (CI) 1.39-1.69], 1.53 (1.37-1.70), and 1.80 (1.62-1.98) for 1 SD decrease in SOS, BUA, and SI, respectively. In men, SOS and SI also predicted total non-spine fractures with HRs similar to those in women. The HR of prediction for hip fracture by SOS and SI was better in the short term than in the long term, and the prediction for hip, wrist, and non-spine fracture remained significant between 5 to 10 years of follow-up. Measurements obtained from heel QUS predicted non-spine fracture in Japanese men and women, and the HRs of Japanese of both genders was similar to the risk ratio (RR) of Caucasian men and women. QUS parameters can predict hip, wrist, and non-spine fracture up to 10 years.