Genetic factors are likely to affect individual cancer risk, but few quantitative estimates of heritability are available. Public health radiation protection policies do not in general take this potentially important source of variation in risk into account. Two surrogate cellular assays that relate to cancer susceptibility have been developed to gain an insight into the role of genetics in determining individual variation in radiosensitivity. These flow cytometric assays for apoptosis induction and cell cycle delay following radiation are sufficiently sensitive to distinguish lymphocytes from a healthy donor population from those of a sample of obligate carriers of ATM mutations (P = 0.01 and P = 0.02, respectively). Analysis of 54 unselected twin pairs (38 dizygotic, 16 monozygotic) indicated much greater intrapair correlation in response in monozygotic than in dizygotic pairs. Structural equation modelling indicated that models including unique environmental factors only fitted the data less well than those incorporating two or more of additive genetic factors, common environmental factors and unique environmental factors. A model incorporating additive genetic factors and unique environmental factors yielded estimates of heritability for the two traits of 68% (95% CI 40-82%, cell cycle) and 59% (95% CI 22-79%, apoptosis). Thus, these data suggest that genetic factors contribute significantly to human variation in these two measures of radiosensitivity that relate to cancer susceptibility.
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Acknowledgments We wish to thank Richard Doull of MRC Har-well for irradiations, Asif Ahmed for technical assistance in the early stages of this work and Prof. Malcolm Taylor of the University of Birmingham for providing AT carrier lymphocytes. This work was funded by the Department of Health Radiation Protection Research Programme, grants RRX 83 and RRX 111. Data collection in the Finn-Twin16 study has been supported by the National Institute on Alcohol Abuse and Alcoholism (grants AA-08315 and AA-12502), the Academy of Finland (Grants 44069 and 100499) and the Academy of Finland Centre of Excellence in Complex Disease Genetics.