DNA repair phenotype and cancer susceptibility--a mini review

Abstract

DNA repair is a complicated biological process, consisting of several distinct pathways, that plays a fundamental role in the maintenance of genomic integrity. The very important field of DNA repair and cancer risk has developed rapidly in the past decades. In this review of selected published data from our laboratory, we describe mostly our work on the study of phenotypic markers of nucleotide excision repair (NER), as measured by the benzo(a)pyrene diol epoxide (BPDE)/ultraviolet (UV)-induced mutagen sensitivity assays, BPDE-induced adduct assay, host cell reactivation (HCR)-DNA repair capacity (DRC) assay, reverse transcription-polymerase chain reaction (RT-PCR) assay and reverse-phase protein lysate microarray (RPP) assay, by using peripheral blood lymphocytes in a series of molecular epidemiological studies. Results of our studies suggest that individuals with reduced DRC have an elevated cancer risk. This finding needs additional validation by other investigators, and we also discussed issues in conducting this kind of research in the future.

Figure 1

Blood sample processing and biomarker assay flow chart. PHA, phytohemagglutinnin; UV, ultraviolet; BPDE, benzo(a)pyrene diol epoxide; CAT, chloramphenicol acetyltransferase; LUC, luciferase; RT-PCR, reverse transcription-polymerase chain reaction. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 2

The relationship between genotypes and phenotypes of the nucleotide excision repair pathway and risk of SCCHN. The numbers on the right are for the common tagging SNPs of each of the 8 core NER genes. NER, nucleotide excision repair; SNP, single nucleotide polymorphism; DRC, DNA repair capacity; SCCHN, squamous cell carcinoma of the head and neck. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]