Influence of Arg399Gln, Arg280His and Arg194Trp XRCC1 gene polymorphisms of Base Excision Repair pathway on the level of 8-oxo-guanine and risk of head and neck cancer in the Polish population

Abstract

BACKGROUND: Reduced efficiency of DNA repair systems has long been a suspected factor in increasing the risk of cancer. OBJECTIVE: In this work we investigate influence of three selected polymorphisms of DNA repair gene XRCC1 and level of oxidative damage (measured as level of 8-oxo-guanine) on modulation of the risk of HNSCC. METHODS: In group of 359 patients with HNSCC (diagnosed with OSCC) the occurrence of polymorphic variants in Arg399Gln, Arg280His and Arg194Trp of XRCC1 were studied with TaqMan technique. In addition we determined level of 8-oxo-guanine with ELISA. RESULTS: Arg399Gln polymorphism and Arg194Trp polymorphism of XRCC1 gene increases the risk of HNSCC. The coexistence of Arg399Gln and Arg194Trp simultaneously enhances this effect. At the same time, their coexistence with His280His raises the risk to a level higher than in the absence of such coexistence, although the His280His itself is not associated with an increased risk of HNSCC. Patients have higher levels of 8-oxo-guanine than control group, and His280His is polymorphism with highest mean value of 8-oxoG level among studied. CONCLUSION: Patients with HNSCC not only have an increased level of 8-oxoguanine and the Arg399Gln and Arg/Trp of XRCC1 modulate risk of cancer, but there is also a relationship between these two phenomena, and it can be explained using intragenic combinations revealing that a high level of 8-oxoG could be a potential mechanism behind the modulation of HNSCC risk by the polymorphisms studied.