Reduced Expression of Human DNA Repair Genes in Esophageal Squamous-Cell Carcinoma in China

Abstract

Epidemiological studies indicated that the incidence of esophageal squamous-cell carcinoma (ESCC) is associated with exposure to a variety of environmental factors. To determine whether the baseline expression of genes involved in DNA damage and repair induced by these carcinogens is associated with higher risk for ESCC, a case-control study was undertaken and the relative expression levels of six DNA repair genes (MGMT, hOGG1, XRCC1, XPD, hMLH1, and hMSH2) were determined in peripheral blood mononuclear cells (PBMC). One hundred patients with newly diagnosed, untreated ESCC and 117 healthy controls matched for age, gender, and residence were recruited. Expression levels of six genes were measured by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR). Compared with controls, the relative expression levels of hMLH1, hMSH2, XRCC1, XPD, and MGMT, were significantly altered in ESCC patients. Using the median of relative expression level in controls as the cutoff point, results also demonstrated an increased risk for ESCC associated with reduced expression of hMSH2, XRCC, XPD, and MGMT. The expression levels of four genes (hMSH2, XRCC1, XPD, MGMT) present in PBMC were significantly correlated with increased risk for ESCC, in which there was reduced expression of MGMT, suggesting an important etiology role for MGMT expression in the initiation of ESCC in Huaian of China.

This work was supported by the National Natural Science Foundation of China (30571540), the Preventive Medicine Foundation of Jiangsu Province (Y200425), and the National Science Development Foundation of Southeast University (XJ0525212). We thank Dr Heike Muenzberg for helpful comments and language revision of the manuscript and Chuzhou Center for Disease Control and Prevention of China for sample collecting and questionnaire survey.