| Identification and monitoring of individuals at high cancer risk would allow for early detection of cancer. Carcinogenesis is a complex gene/environment interaction. Inter-individual cancer susceptibility based on genetics is not well understood, thus the identification of cancer susceptibility genes is a priority. The Environmental Genome Project was established to discover and study potential cancer susceptibility genes. The DNA repair gene XPA is among the genes listed for study. XPA mutations cause the cancer-prone disease xeroderma pigmentosum. We hypothesize that non-xeroderma pigmentosum polymorphic XPA alleles exist and that these genetic variations subtly alter XPA function. Polymorphism detection was performed by sequencing regions containing exons IV, V, and VI of XPA from 184 random pathology specimens. Functional analyses of the Arg228Gln and Val234Leu polymorphic alleles were performed by western blot to determine expression and by survival in response to benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide-(±)- anti (BPDE) exposure to determine XPA function. (Abstract shortened by UMI.)... |
