Citations 12
Mutagen Sensitivity Has High Heritability: Evidence from a Twin Study
Wu, Xifeng , Spitz, Margaret R., Amos, Christopher I., Lin, Jie , Shao, Lina , Gu, Jian , Benowitz, Neal L. , Shields, Peter G. , Swan, Gary E. , Andrade, Mariza de , Gu, Jian
Cancer Research | June 15, 2006 | Volume: 66 | Issue: 12 | Pages: 5993-5996
Abstract 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, γ-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)
Progress in Chemoprevention Drug Development: The Promise of Molecular Biomarkers for Prevention of Intraepithelial Neoplasia and Cancer—A Plan to Move Forward
Kelloff, Gary J. , Lippman, Scott M. , Dannenberg, Andrew J. , Sigman, Caroline C. , Pearce, Homer L., Reid, Brian J. , Szabó, Éva , Jordan, V. Craig , Spitz, Margaret R., Papadimitrakopoulou, Vali A., Lotan, Reuben, Aggarwal, Bharat B. , Bresalier, Robert S. , Kim, Jeri , Lu, Karen H. , Thomas, Melanie E., Rhodes, Helen, Brewer, Molly, Follen, Michele , Shin, Dong M. , Parnes, Howard L. , Siegfried, Jill M. , Evans, Alison A., Blot, William J. , Chow, Wong‐Ho , Blount, Patricia L., Wang, Kenneth K. , Lam, Stephen , Lee, J. Jack, Dubinett, Steven M., Engstrom, Paul F., Meyskens, Frank L. , O’Shaughnessy, Joyce , Hawk, Ernest T. , Levin, Bernard, Nelson, William G. , Hong, Waun Ki , Prevention, for the AACR Task Force on Cancer, Lee, J. Jack , Mills, Gordon B. , Arun, Banu , Maley, Carlo C. , Lee, J. Jack, Prevention, for the AACR Task Force on Cancer, Szabo, Eva , Lee, J Jack
Clinical Cancer Research | June 8, 2006 | Volume: 12 | Issue: 12 | Pages: 3661-3697
AbstractThis article reviews progress in chemopreventive drug development, especially data and concepts that are new since the 2002 AACR report on treatment and prevention of intraepithelial neoplasia. Molecular biomarker expressions involved in mechanisms of carcinogenesis and genetic progression models of intraepithelial neoplasia are discussed and analyzed for how they can inform mechanism-based, molecularly targeted drug development as well as risk stratification, cohort selection, and end-point selection for clinical trials. We outline the concept of augmenting the risk, mechanistic, and disease data from histopathologic intraepithelial neoplasia assessments with molecular biomarker data. Updates of work in 10 clinical target organ sites include new data on molecular progression, significant completed trials, new agents of interest, and promising directions for future clinical studies. This overview concludes with strategies for accelerating chemopreventive drug development, such as integrating the best science into chemopreventive strategies and regulatory policy, providing incentives for industry to accelerate preventive drugs, fostering multisector cooperation in sharing clinical samples and data, and creating public-private partnerships to foster new regulatory policies and public education.