1.5, 7.5) for malignant tumors, higher than any of the ERR/Sv shown in Table 6-2, although very uncertainly estimated. The ERRs/Sv was 0.7 (0.1, 1.7) for benign tumors. Most of the dose-response for malignant tumors resulted from mucoepidermoid carcinoma with an ERR/Sv of 8.3 (2.5, 29.6), whereas most of the dose-response for benign tumors resulted from Warthin’s tumor with an ERR/Sv of 3.1 (0.6, 10.3).

Stomach Cancer

This site merits special comment primarily because stomach cancer is the most common type of cancer in Japan and, specifically, in the LSS cohort. Based on cancer incidence data evaluated by Thompson and colleagues (1994), stomach cancer had a relatively small but precisely estimated ERR/Sv of 0.32 (0.16, 0.50). The ERR/Sv for females was about three times that for males, and the ERR/Sv decreased with increasing age at exposure. Nearly one-third (31%) of the solid cancer cases included in the incidence data were stomach cancers, so this cancer potentially has a strong impact on overall solid cancer results. However, analyses of solid cancer mortality data with stomach cancer excluded resulted in parameter estimates that were similar to those obtained for all solid cancers (Preston and others 2003).

Liver Cancer

Liver cancer is one of the most frequently occurring cancers in Japan and the third most common cancer (after stomach and lung) in the LSS. Liver cancers reported on death certificates might in fact be cancers originating in other organs because the liver is a frequent site for metastatic cancer. This can be a problem even for tumor registry data, since some cases were based only on death certificate information. For this reason, Cologne and colleagues (1999) conducted a study of primary liver cancer based on extensive pathology review of known or suspected cases of liver cancer. This study showed a clear dose-response with an estimated ERR/Sv (with 95% CI) of 0.81 (0.32, 1.43). The ERRs/Sv for males and females were very similar (0.81 and 0.78, respectively), in contrast to findings for many other cancers, and somewhat remarkable given that background rates for males were about three times those for females. The modifying effect of age at exposure was also different from that for other cancers, with excess risk peaking for those exposed in their twenties, but little evidence of excess risk for those exposed under age 10 or over age 45.

Of the 364 cases analyzed, there were 307 hepatocellular carcinomas (HCCs), 53 cholangiocarcinomas, two mixed hepatocellular-cholangiocarcinomas, and one each of hepatoblastoma and hemangiosarcoma. This is in contrast to liver cancers associated with Thorotrast exposure, which are dominated by cholangiocarcinomas and hemangiosarcomas. Cologne and colleagues found no difference in the dose-response for HCC compared to cholangiocarcinoma, although this may have been because the number of cancers of the latter type was small.

It has been estimated that more than 60–75% of HCC cases in Japan are related to chronic hepatitis C infection and that 20–25% are positive for hepatitis B surface antigen (Fujiwara and others 2000). Neriishi and others (1995) reported a radiation dose related increase in the prevalence of hepatitis B surface antigen in atomic bomb survivors. Fujiwara and colleagues (2000) did not find such a relationship for hepatitis C infection, but their data suggest that the radiation dose-response for chronic liver disease was greater for survivors who were positive for hepatitis C antibody than for survivors who were negative.

Lung Cancer

Next to stomach cancer, lung cancer was the most common cancer in the LSS cohort. This cancer showed a strong sex association with the ERR/Sv for females about four times as large as that for males based on the incidence data evaluated by Thompson and colleagues (1994), which probably reflects at least in part the larger baseline risks for males. Lung cancer also deviated from the usual pattern of decreasing risk with increasing age at exposure. Instead, lung cancer risks appeared, if anything, to increase with increasing age at exposure, although, based on the incidence data, this trend was not statistically significant.

Recently, Pierce and coworkers (2003) evaluated the joint effects of smoking and radiation on lung cancer incidence through 1994 in a subset of about 45,000 members of the LSS cohort for whom both radiation dose and smoking data were available. The smoking data were obtained from mail surveys of the LSS cohort and clinical interviews of members of the AHS conducted during 1963–1993. Pierce and colleagues (2003) found that the effects of smoking and radiation were significantly submultiplicative and consistent with an additive model. They note that the aging of the cohort and higher smoking levels among more recent birth cohorts resulted in a stronger basis for evaluating the joint effects of smoking and radiation than in previous analyses by Kopecky and colleagues (1986), Prentice and colleagues (1983), and the National Research Council (NRC 1988); these earlier investigations were unable to distinguish between additive and multiplicative effects. Pierce and colleagues (2003) also found that adjustment for smoking substantially reduced the female-to-male ERR/Sv ratio; about 85% of the men and 16% of the women were smokers. With adjustment for smoking, there was evidence of a decline in the ERR/Sv with increasing attained age (comparable to other solid cancer sites), but no evidence of modification by age at exposure.

Skin Cancer

Ron and colleagues (1998b) conducted a detailed study of skin cancer that included pathologic review of cases. Basal cell carcinoma (80 cases) was found to be associated with



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