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Polymorphisms in Genes Involved in DNA-Damage Processing and Their Effect on Cancer Risk (pp. 113-124) $100.00
Authors:  (G. Iarmarcovai, A. Botta, T. Orsière, Laboratory of Biogenotoxicology and Environmental Mutagenesis, Faculty of Medecine, Université de la Méditerranée, France, S. Bonassi, Unit of Molecular Epidemiology, National Cancer Research Institute, Genoa, Italy, R.A. Baan, Carcinogen Identification and Evaluation Group, WHO - International Agency for Research on Cancer, France)
Abstract:
The individual response to genotoxic stress and induction of DNA damage may vary
according to various conditions, such as the absorption and metabolism rate of genotoxic
agents, the extent and efficacy of DNA-damage induction and repair, the balance
between apoptosis and necrosis of exposed cells, the proper functioning of cell-cycle
control, and the immune response. All of these processes are governed by certain genes
or combinations of genes. Numerous human population studies have evaluated the
relationship between genetic polymorphisms and DNA-damage induction and repair in
response to genotoxic insult. The most common type of variation in DNA sequence is the
single-nucleotide polymorphism, present in about 1 per 1,000 nucleotides in the human
genome. However, the role of this type of genetic variant contributing to diseases with a
complex etiology such as cancer is poorly understood. Hundreds of polymorphisms in
genes that encode enzymes involved in the metabolism of xenobiotics (such as
oxidoreductases, P450 cytochromes, glutathione S-transferases, N-acetyl transferases,
methyltransferases, hydrolases, dehydrogenases), in DNA repair (participating in direct
reversal repair, base-excision repair, nucleotide-excision repair, and double-strand-break
repair), and in folate metabolism (methylenetetrahydrofolate reductase, methionine
synthase, methionine synthase reductase) have been identified, although for many of
these polymorphisms the impact on repair phenotype and cancer susceptibility remains
uncertain. The present article reviews which of the many single-nucleotide
polymorphisms in genes involved in DNA-damage processing influence cancer risk, and
provides insight into the complexity of the genotype-phenotype relationship.
Nevertheless, when a specific polymorphism by itself appears to have no or only a weak
effect, the identification and characterization of the combined effects of different
susceptibility genes for cancer risk require the understanding of gene-gene interactions. 


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Polymorphisms in Genes Involved in DNA-Damage Processing and Their Effect on Cancer Risk (pp. 113-124)