Oxidative DNA damage and human esophageal cancer risk in Huaian, China

Oxidative DNA damage plays important role in carcinogenesis and 8-hydroxy-2'-deoxyguanosine (8-OHdG), the most common oxidative DNA damage biomarker, has been shown to associate with formation of several cancer sites, while its role in esophageal cancer remains unclear. Therefore, we conducted a population-based case-control study, with 189 esophageal squamous cell carcinoma (ESCC) cases and 524 age-, gender-, and residency-matched healthy controls recruited from Huaian, China, a high risk area of ESCC. Levels of 8-OHdG in morning urine was determined by solid-phase extraction coupled with HPLC- electrochemical detection and adjusted by urinary creatinine. hOGG1 is responsible for repairing oxidative DNA damage and its single nucleotide polymorphism (Ser326Cys) was determined by PCR/RFLP. The average urinary 8-OHdG level in case group was 49.56 ± 235.66 ng/mg creatinine (mean±SD; range: 1.28 – 3210.23, median: 22.04). The average urinary 8-OHdG level in the control group was 23.30 ± 47.32 ng/mg creatinine (range: 0.71 – 817.22, median: 13.71). Levels of 8-OHdG were significantly higher in cases than controls (p <0.0001), and the difference remained significant (p <0.001) after adjusted by age and gender. A marginal significant difference was observed in comparison of distribution of hOGG1 genotypes in cases and controls (p=0.07) with wild type (ser/ser) 38 (20.88%) in cases vs. 70 (14.46%) in controls, heterozygote (ser/cys) 79 (43.41%) in cases vs. 251 (51.86%) in controls, and mutant type (cys/cys) 65 (35.71%) in cases vs. 163 (33.68%) in controls. These results support the role of oxidative DNA damage in the development to esophageal cancer in this high-risk population.