most cohorts with suitable data for developing quantitative risk models, analyses based on models similar to those used by the committee have been conducted and published. This facilitated the committee’s evaluation of data from other studies. Pooled analyses of thyroid cancer risks (Ron and others 1995a) and of breast cancer risks (Preston and others 2002a) were especially helpful in this regard, as were several meta-analyses by Little and colleagues. In addition, the many published analyses based on A-bomb survivor data have guided and facilitated the committee’s efforts in its choice of models. The committee notes particularly the main publications on mortality (Preston and others 2003) and incidence data (Thompson and others 1994) and the models developed by UNSCEAR (2000b) and NIH (2003).

The use of data on persons exposed at low doses and low dose rates merits special mention. Of these studies, the most promising for quantitative risk assessment are the studies of nuclear workers who have been monitored for radiation exposure through the use of personal dosimeters. These studies, which are reviewed in Chapter 8, were not used as the primary source of data for risk modeling principally because of the imprecision of the risk estimates obtained. For example, in a large combined study of nuclear workers in three countries, the estimated relative risk per gray (ERR/Gy) for all cancers other than leukemia was negative, and the confidence interval included negative values and values larger than estimates based on A-bomb survivors (Cardis and others 1995).

Since the publication of BEIR V, data on cancer incidence in the LSS cohort from the Hiroshima Tumor Registry have become available, whereas previously only data from the Nagasaki Tumor Registry were available. Thus, the committee could use both incidence and mortality data to develop its models. The incidence data offer the advantages of including nonfatal cancers and of better diagnostic accuracy. However, the mortality data offer the advantages of covering a longer period (1950–2000) than the incidence data (1958–1998) and of including deaths of LSS members who migrated from Hiroshima and Nagasaki to other parts of Japan.

MEASURES OF RISK AND CHOICE OF CANCER END POINTS

To express the health impact of whole-body exposures to radiation, the lifetime risk of total cancer, without distinction as to site, is usually of primary concern. Estimates of risk for both mortality and incidence are of interest, the former because it is the most serious consequence of exposure to radiation and the latter because it reflects public health impact more fully. The time or age of cancer occurrence is also of interest, and for this reason, estimates of cancer mortality risks are sometimes accompanied by estimates of the years of life lost or years of life lost per death. Because leukemia exhibits markedly different patterns of risk with time since exposure and other variables, and also because the excess relative risk for leukemia is clearly greater than that for solid cancers, all recent risk assessments have provided separate models and estimates for leukemia.

For exposure scenarios in which various tissues of the body receive substantially different doses, estimates of risks for cancers of specific sites are needed. Adjudication of compensation claims for possible radiation-related cancer, which is usually specific to organ site, also requires site-specific estimates. Furthermore, site-specific cancers vary in their causes and baseline risks, and it might thus be expected that models for estimating excess risks from radiation exposure could also vary by site. For this reason, even for estimating total cancer risk, it is desirable to estimate risks for each of several specific cancer sites and then sum the results.

The development of site-specific models is limited by data characteristics. For A-bomb survivor data on solid cancers, parameter estimates based on site-specific data are less precise than those based on all solid cancers analyzed as a group, particularly for less common cancers. It is especially difficult to detect and quantify the modifying effects of variables such as sex, age at exposure, and attained age for site-specific cancers. It was for these reasons that the BEIR V committee provided estimates for only five broad cancer categories.

In addition to statistical uncertainties, it has recently been recognized that estimates of the modifying effects of age at exposure based on A-bomb survivor data can be influenced strongly by secular trends in Japanese baseline rates (Pierce 2002; Preston and others 2003). This occurs because age at exposure in the LSS cohort is confounded with birth cohort, making it impossible to estimate their separate effects without additional information on the relation of baseline and radiation-related risks. (See Annex 12B for further discussion of this issue.) Japanese rates for several cancer sites changed over the period 1950–1998 as Japan became more Westernized, including rates for cancers of the stomach, colon, lung, and female breast. A related problem is that baseline risks for the United States and Japan differ substantially for many cancer sites, and it is unclear how to account for these differences in applying models developed from A-bomb survivor data to estimate risks for the U.S. population.

Pierce and colleagues (1996) and, more recently, Preston and colleagues (2003) found little evidence of heterogeneity among excess relative risk (ERR)1 models developed for several specific cancer sites. Although these authors caution that this finding should be taken mainly as a warning against overinterpreting apparent differences in sites, some grouping of cancers seems justified. In developing its models, the committee has tried to strike a balance between allowing for differences among cancer sites and statistical precision. As discussed later in this chapter, most of the committee’s mod-

1  

ERR is the rate of disease in an exposed population divided by the rate of disease in an unexposed population minus 1.0.



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