Validation of the cell cycle G(2) delay assay in assessing ionizing radiation sensitivity and breast cancer risk.

Genetic variations in cell cycle checkpoints and DNA repair genes are associated with prolonged cell cycle G(2) delay following ionizing radiation (IR) treatment and breast cancer risk. However, different studies reported conflicting results examining the association between post-IR cell cycle delay and breast cancer risk utilizing four different parameters: cell cycle G(2) delay index, %G(2)-M, G(2)/G(0)-G(1), and (G(2)/G(0)-G(1))/S. Therefore, we evaluated whether different parameters may influence study results using a data set from 118 breast cancer cases and 225 controls as well as lymphoblastoid and breast cancer cell lines with different genetic defects.

DNA damage levels in prostate cancer cases and controls.

This study used the alkaline Comet assay to evaluate whether basal or H2O2-induced DNA damage is associated with prostate cancer (CaP) risk. Using lymphocyte samples from 158 CaP cases and 128 controls, collected in an ongoing case-control study, our results showed that basal DNA damage did not differ between cases and controls. However, the H2O2-induced DNA damage level was significantly higher in incident cases (mean +/- SD; 6.

Nucleotide-excision repair and prostate cancer risk.

Prostate cancer (CaP) is the most commonly diagnosed nonskin cancer and the second leading cause of cancer death in American men. Its etiology is not fully understood. Ethnicity/race and family history are associated with it, and incidence increases with age.

The ADPRT V762A genetic variant contributes to prostate cancer susceptibility and deficient enzyme function.

The ADP-ribosyltransferase (ADPRT) gene encodes a zinc-finger DNA-binding protein, poly(ADP-ribose) polymerase-1 (PARP-1), that modifies various nuclear proteins by poly(ADP-ribosyl)ation and functions as a key enzyme in the base excision repair pathway. We have conducted two studies to test whether an amino acid substitution variant, ADPRT V762A (T2444C), is associated with prostate cancer (CaP) risk and decreased enzyme function. The first study used genomic DNA samples from an ongoing, clinic-based case-control study (488 cases and 524 controls) to show that a higher percentage of the CaP cases carried the ADPRT 762 AA genotype than controls (4% versus 2%).