Clinical Significance of ERCC2, XPC, ERCC5 and XRCC3 Gene Polymorphisms in Diffuse Large B Cell Lymphoma

Abstract

Objectives: DNA repair genes protects the genome from DNA damage both of endogenous and exogenous stress factors. Due to DNA repair gene polymorphisms, there are differences in the repair capacity between several cancer types.The aim of this study is to evaluate the association between some of the DNA repair gene polymorphisms and clinicaloutcome in Diffuse Large B-Cell Lymphoma (DLBCL).Methods: The association between clinical factors including stage at diagnosis, extra-nodal involvement, tumor burden, bone marrow involvement, relapse status, disease-free/overall survival times and DNA repair gene polymorphismsincluding ERCC2 (Lys751Gln), XPC (Gln939Lys), ERCC5 (Asp1104His) and XRCC3 (Thr241Met) in 58 patients with DLBCL.T-Shift Real-Time PCR was used to detect these mutations.Results: The median survival times were 60 months and 109 months in patients with CC genotype and CA/AA genotype of XPC gene polymorphism, respectively (p=0.017). More interestingly, median survival times were 9 months and109 months in patients with CC (XPC)/CC (XRCC3) and CA/AA (XPC)/CT/TT (XRCC3) for both XPC and XRCC3 genepolymorphisms, respectively (p=0.004). Six of 18 patients with CC genotype for XPC (Gln939Lys) had bone marrowinvolvement while only one of 40 patients with CA and AA genotype of XPC (Gln939Lys) gene polymorphism hadbone marrow involvement at diagnosis. Statistical analysis failed to show significant relationship between other genepolymorphisms and survival times. Cox Regression analysis standardized by age, stage and bone marrow involvementshowed that IPI, XPC and XRCC3 gene polymorphisms were independent factors for OS.Conclusion: XPC and XRCC3 gene polymorphisms may be important for clinical presentation and OS in DLBCL. However this study involves relatively low number of cases and these polymorphisms must be studied in larger studies toconfirm our results.