ERCC1, a potentially useful marker of cancer susceptibility related to DNA repair deficiency

B86 DNA repair defects have been historically associated with cancer prone conditions. Xeroderma pigmentosum and similar diseases demonstrate the impact that DNA repair deficiency can have on the human host. There exists the possibility that more subtle defects in DNA repair capability may be associated with a grossly normal human phenotype, but associated with predisposition to developing cancer in multiple different organs. Nucleotide excision repair (NER) is responsible for the repair of DNA damage induced by ultraviolet light, and polycyclic aromatic hydrocarbons (PAHs). We have reviewed published data spanning over the last ten years to develop an overview of the possible relationship between selected defects in NER, and cancer susceptibility. Understanding this relationship may lead to more effective targeting of cancer prevention strategies. Collectively, the published data shows that persons with subtle defects in genes involved in NER are at increased risk for the following cancers: lung (NSCLC), head and neck, basal cell ca of the skin, gliomas of the brain, breast, ovarian, colorectal, endometrial, bladder, renal cell, ALL and AML. Most but not all of these tumors have a well-established epidemiologic relationship with smoking (exposure to PAHs). Subtle defects in NER are suggested in each of these malignancies by the demonstration of relevant polymorphisms of genes that are important in the NER pathway. Eight of the twelve cancers listed above are associated with abnormalities seen in the gene ERCC1 . These cancers are: NSCLC, head and neck, gliomas, breast, ovarian, colorectal, bladder and ALL. This review forms the foundation for ongoing work to assess the potential role of ERCC1 , and other NER genes, as molecular tools in developing genomic strategies for cancer prevention and control.