Hprt mutant frequencies, nonpulmonary malignancies, and domestic radon exposure: "Postmortem" Analysis of an interesting hypothesis

The hypothesis that exposure to domestic radon raises the risk For leukemia and other nonpulmonary cancers has been proposed and tested in a number of epidemiologic studies over the past decade. During this period, interest i n this hypothesis was heightened by evidence of increased Frequencies of mu tations at the hypoxanthine guanine phosphoribosyl transferase (hprt) gene in persons exposed to domestic radon (Bridges BA et al. [1991]. Lancet 337: 1 187-1 189). An extension of this study (Cole J et al. [lsqb[1996]: Radiat Res 145:61-69) and two independent studies (Albering HJ et al. [1192[: Lan cet 340:739; Albering KI et al. [1994[: lancet 344:750-751) Found that hprt mutant frequency was not correlated with domestic radon exposure, and two well-designed epidemiologic studies showed no evidence of a relation betwee n radon exposure and leukemia in children or adults. In this report, we pre sent additional data from a study of Colorado high school students showing no correlation between domestic radon exposure and hprt mutant frequency. W e use reanalyses of previous studies of radon and hprt mutant frequency to identify problems with this assay as a biomarker for domestic radon exposur e and to illustrate difficulties in interpreting the statistical data. We a lso show with analyses of combined data sets that there is no support For t he hypothesis that domestic radon exposure elevates hprt mutant frequency. Taken together, the scientific evidence provides a useful example of the pr oblems associated with analyzing and interpreting data that link environmen tal exposures, biomarkers, and diseases in epidemiologic studies. (C) 2001 Wiley-Liss, Inc.