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The scientific impetus for the pooling of the case-control studies began with discussions
among members of the Biological Effects of Ionizing Radiation (BEIR) IV Committee
during the mid-1980s (NRC, 1988). The committee reviewed the small number of
published case-control studies and those planned, and two of its members, Jay Lubin
and myself, joined Clarice Weinberg to publish a paper on sample size needs for case-
control studies of indoor radon (Lubin et al., 1990). The potential limitations of the
planned and in-progress studies were immediately evident: in the face of plausible
levels of measurement error, the needed sample sizes were generally much greater
than those of the individual studies, particularly for evaluation of possible differences in
the risks for exposures in homes and in mines.
Planning for pooling of the individual studies was proposed as the best solution to the
unavoidable problem of measurement error and the inadequate sample sizes of the
individual studies. Two of the major funders of radon research at the time, the U.S.
Department of Energy and the Commission of European Communities, were easily
convinced that a planning effort should be put in place for eventual pooling of the case-
control studies of indoor radon and lung cancer around the world. Together, they
supported three investigator workshops, which took place in 1989, 1991, and 1995. The
investigators carrying out the case-control studies were eager participants in the
workshops and quickly established the collaborations that continued separately in North
America and Europe and that will eventually lead to a pooling of all of the major studies.
The investigators are to be congratulated for participating in this collaborative project
that will give the most precise estimates possible of the lung cancer risk associated with
indoor radon. The funders, both of the subsequent workshops and of the pooling efforts,
also should be acknowledged.
CURRENT DEVELOPMENTS
In the last several decades, there have been many scientific advances around radon
and lung cancer that have reduced some of the uncertainties that first prompted the
case-control studies. First, the data from 11 cohort studies of underground miners have
been pooled and exposure-response relationships have been characterized; the sample
size also made possible analyses in never smokers in the cohorts, and in those having
low exposures (<400 WLM) (NRC, 1999). The analyses of the underground miners
having the lowest levels of exposure indicate a linear relationship of exposure with risk.
Second, increasingly elegant experimental studies have documented the occurrence of
permanent damage to a cell from just one hit by an alpha particle (NRC, 1999). This
experimental finding suggests that assuming a linear nonthreshold relationship between
exposure and risk at the levels found indoors is biologically appropriate. In this same
type of experimental system, a bystander mutagenic effect has been demonstrated that
affects cells adjacent to a cell damaged by a single alpha particle (Hall & Hei, 2003).
This effect may amplify the risks of radon exposure beyond those anticipated based on
the construct that passage of an alpha particle through a cell damages only that cell.
Third, the results of the present analysis were anticipated with the earlier meta-analyses
of the indoor studies (NRC, 1999).