Association of XRCC6 C1310G and LIG4 T9I polymorphisms of NHEJ DNA repair pathway with risk of colorectal cancer in the Polish population

Introduction: Colorectal cancer is the second most common cancer worldwide. DNA double strand breaks (DSBs) are the most dangerous lesions which can lead to carcinogenesis. Nonhomologous end joining (NHEJ) is an important pathway that allows for recovering DNA by direct end joining. The XRCC6 and LIG4 genes encode respectively Ku70 protein and human ATP-dependent DNA ligase, which are the components of the NHEJ repair pathway. The aim of our study was to evaluate the influence of XRCC6 C1310G and LIG4 T9I gene polymorphisms on colorectal cancer risk in the Polish population. Materials and method: Genotyping was performed using TaqMan probes based on the analysis of PCR products amplified in Real Time PCR. The research was carried out on the material obtained from 100 patients with colorectal cancer and 100 cancer-free individuals who were age- and sex-matched as a control group. The results were developed using the chi-square test and odds ratio (OR). Results: Odd ratio analysis indicates reduced risk of colorectal cancer for LIG4 T9I polymorphism in heterozygous model C/T (OR = 0.2717 95% CI = 0.1247-0,5918) and homozygous model T/T (OR= 0.3593 95% CI = 0.1394-0.9266). A similar situation was observed for XRCC6 C1310G gene polymorphism - a heterozygous variant C/G (OR = 0.1181 95% CI = 0.0145-0.964) and homozygous variant G/G (OR = 0.0972 95% CI = 0.0097-0.9713) were connected with a decreased risk of colorectal cancer. Conclusions: Our research revealed that XRCC6 C1310G and LIG4 T9I polymorphisms are associated with diminished risk of colorectal cancer. However, to confirm the obtained results, further investigations should be carried out.