Association of base excision repair pathway genes OGG1, XRCC1 and MUTYH polymorphisms and the level of 8-oxo-guanine with increased risk of colorectal cancer occurrence

Abstract

Objectives: Reduced efficiency of DNA repair systems has long been a suspected factor in increasing the risk of cancer. In this work authors investigate influence of selected polymorphisms of DNA repair genes (XRCC1, OGG1 and MUTYH) and level of oxidative damage (measured as level of 8-oxo-guanine, 8-oG) on modulation of the risk of colorectal cancer.

Material and methods: In group of 324 patients with colorectal cancer the occurrence of polymorphic variants in Ser326Cys of OGG1, Arg399Gln of XRCC1 and Gln324His of MUTYH were studied with TaqMan technique. In addition level of 8-oG in isolated DNA was determined.

Results: Studied polymorphisms of OGG1, XRCC1 and MUTYH genes influence the risk of CRC: OGG1 Ser326Cys (OR = 1.259, 95% CI: 1.058-1.499, p = 0.007), XRCC1 Arg399Gln (OR = 2.481, 95% CI: 1.745-3.529, p < 0.0001) and MUTYH Gln324His (OR = 1.421, 95% CI: 1.017-1.984, p = 0.039) increase the risk. At the same time, studies examined level of 8-oG for each of the genotypes in both the patient and control group, and have shown that OGG1 Ser326Cys and XRCC1 Arg399Gln are associated with elevated 8-oG level, while MUTYH Gln324His is not, suggesting, that in case of OGG1 Ser326Cys and XRCC1 Arg399Gln CRC risk modulation is connected to mechanisms associated with 8-oG levels.

Conclusions: This work shows that patients with CRC not only have an increased level of 8-oG and that the studied polymorphisms modulate risk of cancer, but also indicate a relationship between these 2 phenomena, which may contribute to a better understanding of the mechanism of neoplastic process in case of reduced effectiveness of DNA repair mechanisms. Int J Occup Med Environ Health. 2022;35(5):625-33.

Keywords: DNA repair; MUTYH; OGG1; XRCC1; cancer; oxidative stress.