Abstract
Three case-control studies of DNA repair in the general population were conducted with: i. 88 primary basal cell carcinoma (BCC) cases and 135 cancer-free controls, ii 304 study subjects including 57 arsenical cancer patients and 247 noncancerous controls in Taiwan and iii 41 breast cancer patients and 73 controls. The host reactivation assay was used to measure cellular DRC capacity with cryopreserved peripheral lymphocytes from both the cases and their controls. In study i. reduced repair of UV-induced DNA damage contributed to the risk of sunlight-induced BCC. A family history of BCC is a predictor of low DNA repair. Repair of UV damaged DNA declines at a rate of about 0.6 per annum in in non-cancerous controls. In addition, reduced DNA repair is more likely seen in young BCC cases, indicating that BCC is a premature aging disease of the skin. The persistence of photochemical damage because of reduced repair, results in point mutations in the p53 gene and allelic loss of the nevoid BCC (Gorlin’s syndrome) gene located on chromosome 9q. Xeroderma pigmentosum appears to be a valid paradigm for the role of DNA repair in BCC in the general population. An extension of these studies led to conclusions from Black Foot Disease (BDF) studies that DRC by itself is not a risk factor for arsenical skin cancer, but those individuals with low DRC,are at much greater risk when exposed to high levels of arsenic in their drinking water or when they are on poor diets. DRC, therefore, appears to be a susceptibility factor in this disease. Further DRC is consistently lower in breast cancer cases than in controls and appears to be a susceptibility factor in breast cancer and DRC in lymphocytes may be employed as a biomarker for human breast cancer risk.