Although these data suggest that the polymorphisms have functional relevance, biochemical and biological characterization of the variants are needed to validate the findings.BER involves excision of the damaged region followed by repair synthesis using the opposite strand as the template.The XRCC protein complexes with DNA ligase III, DNA polymerase, and poly. A polymorphism at XRCC site of codon in exon results in a nonconservative amino acid substitution of arginine for glutamine.The polymorphism at XRCC site of codon in exon results in a nonconservative amino acid substitution of arginine for tryptophan. We used bleomycininduced bc data from lung cancer cases and controls to correlate with genotype data, because bleomycin induces strand breaks requiring BER genotype exhibited higher numbers of bleomycininduced bc than those with the combined variant genotype. Similarly, among both the cases and the controls, individuals with the homozygous variant genotype at exon exhibited higher bc than those with the wildtype genotype, with evidence of a gene dosage effect, although the trend was not statistically significant.The DNA repairdeficient cell line, EM, which has high background SCE frequencies, has a mutation in XRCC at codon. This cell line is also sensitive to accumulation of singlestrand DNA breaks after damage.The XRCC codon is located within the BRCT domain, and that is present in many DNA damage response and cellcycle checkpoint proteins.Because the role of XRCC in BER brings together DNA polymerase, DNA ligase III, and poly polymerase at the site of DNA damage, the exon variant could have an altered repair activity.There have been a few previous studies evaluating the functional significance of these polymorphisms.No differences were detected with the codon genotype.However, there are many issues that need to be addressed.These issues include selection bias, variability and reliability of the tests, and the retrospective nature of the study designs, raising concerns about the impact of disease status on the assay results.We also need to know how well these functional data reflect events at the level of the target tissue.Molecular epidemiologists will increasingly be called on to identify highrisk subgroups who might benefit disproportionately from screening or chemoprevention interventions.Additional studies in these highrisk individuals can also provide insight into applying these approaches to the average risk population.Surrogate markers found to be most representative of molecular reasch Azelastine hydrochloride changes in the target tissue will be used to develop quantitative risk assessment models.Furthermore, these markers are of potential value as an adjunct to new screening modalities, such as spiral computed tomography of the lung.These approaches can also be applied to other readily accessible tissues or fluids such as urine, stool, or sputum, that provide an opportunity for relatively noninvasive evaluation of risk, and of physiological and pathophysiological states.Pharmacogenetic profiles could be used to individualize therapy and to understand the functional consequences of chemoprevention, chemotherapy, or radiotherapy response.Identification of protein patterns in serum using highthroughput proteomics linked to novel bioinformatics approaches can be useful for studying the entire spectrum from predisposition to early diagnosis and cancer outcome.Tumor DNA can be isolated from serum or plasma, as a useful source for screening specific transcripts or mutations in mitochondrial or nuclear DNA sequences, and that may have a potential role in early detection.