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Mutagen Sensitivity Has High Heritability: Evidence from a Twin Study

¹ Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas; ² Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; ³ University of California-San Francisco, California; ⁴ Cancer Genetics and Epidemiology, Lombardi Comprehensive Cancer Center, Washington, District of Columbia; and ⁵ Center for Health Sciences, SRI International, Menlo Park, California

Requests for reprints: Xifeng Wu, Department of Epidemiology, Unit 1340, The University of Texas M.D. Anderson Cancer Center, 1155 Pressler Boulevard, Houston, TX 77030. Phone: 713-745-2485; Fax: 713-792-4657; E-mail: xwu{at}mdanderson.org.

Despite numerous studies showing that mutagen sensitivity is a cancer predisposition factor, the heritability of mutagen sensitivity has not been clearly established. In this report, we used a classic twin study design to examine the role of genetic and environmental factors on the mutagen sensitivity phenotype. Mutagen sensitivity was measured in peripheral blood lymphocytes from 460 individuals [148 pairs of monozygotic (MZ) twins, 57 pairs of dizygotic (DZ) twins, and 50 siblings]. The intraclass correlation coefficients were all significantly higher in MZ twins than in dizygotes (DZ pairs and MZ-sibling pairs combined) for sensitivity to four different mutagen challenges. Applying biometric genetic modeling, we calculated a genetic heritability of 40.7%, 48.0%, 62.5%, and 58.8% for bleomycin, benzo[a]pyrene diol epoxide, -radiation, and 4-nitroquinoline-1-oxide sensitivity, respectively. This study provides the strongest and most direct evidence that mutagen sensitivity is highly heritable, thereby validating the use of mutagen sensitivity as a cancer susceptibility factor. (Cancer Res 2006; 66(12): 5993-6)

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