Cellular Defenses Against Radiation-Induced Carcinogenesis:

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TAKE-HOME MESSAGE • <strong>Radiation</strong> has many advantages as a model carcinogen for studying gene-environment (G-E) interactions in cancer. • BCC has many advantages as a cancer model for G-E interactions. • DNA repair genes in the NER pathway are prime candidates for G-E interaction in BCC. • Genes in Hedgehog pathway may also be very important to BCC etiology. • Cell cycle, apoptosis, and other pathways may play a role in BCC, but the evidence is weaker. • Care must be taken to avoid confounding genes, such aging and skin color related genes. • Dose should be viewed as a powerful affect modifier and potential confounder. • There is probably a strong multiplicative interaction between age of onset and BCC RR, that needs to be adjusted for. • Genes involved in BCC are probably important for other cancers as well. NCI REB <strong>Radiation</strong> Epidemiology Course, May 14, 2007 TJJ
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Cellular Defenses Against Radiation
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GOALS: • Provide an overall descr
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NCI REB Radiation Epidemiology Cour
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Cancer cells “evolve” into a hi
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WHY CHECKPOINTS Fidelity of cell di
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Cyclin/CDK complexes seem to be reg
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• At least two checkpoints are re
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DO DEFECTIVE CHECKPOINTS CAUSE CANC
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Radiation-Induced G2 delay in lymph
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Rothkamm and Lobrick, PNAS, 2003 NC
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Somatic Mutation and Cancer Environ
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Major DNA repair pathways: • Non-
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“… the failure of DNA repair in
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T. Lindahl and R.D. Wood, Science 2
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NER PATHWAY GENES GENE ALIASES DESC
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Mismatch repair associated tumors i
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Non-Homologous End Joining (NHEJ) N
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Illegitimate Recombination NCI REB
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TARGET THEORY NCI REB Radiation Epi
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A-T CELL CANCER CELL DEATH NCI REB
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OTHER TARGET QUESTIONS: • If DNA
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Mutations in Chk2 produce the Li-Fr
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CASE STUDY: Finding Molecular Targe
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Environmental Causes of BCC • UV
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UV DAMAGE TO DNA NCI REB Radiation
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Page 71 and 72: For BCC, PTCH may be even a bigger
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Page 113 and 114: Aging genes (I.e. non-DNA repair) A
Page 115 and 116: RR for XP patients by age 8000 8000
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