Association of Germline CHEK2 Gene Variants with Risk and Prognosis of Non-Hodgkin Lymphoma

摘要: The checkpoint kinase 2 gene (CHEK2) codes for the CHK2 protein, an important mediator of DNA damage response pathway. CHEK2 has been recognized as a multi-cancer susceptibility gene; however, its role in non-Hodgkin lymphoma (NHL) remains unclear. We performed mutation analysis entire coding sequence 340 NHL patients using denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA). Identified hereditary variants were genotyped 445 non-cancer controls. influence on disease risk was statistically evaluated. germline included four truncating mutations (found five no control; P = 0.02) nine missense 21 12 controls; 0.02). Carriers non-synonymous had increased development [odds ratio (OR) 2.86; 95% confidence interval (CI) 1.42–5.79] unfavorable prognosis [hazard (HR) progression-free survival (PFS) 2.1; CI 1.12–4.05]. In contrast, most frequent intronic variant c.319+43dupA (identified 22% 31% controls) associated with decreased (OR 0.62; 0.45–0.86), but positive prognostic effect limited to diffuse large B-cell (DLBCL) treated by conventional chemotherapy without rituximab (HR-PFS 0.4; 94% 0.17–0.74). Our results show that germ-line affecting protein confer moderately-increased NHL, they are prognosis, may represent valuable predictive biomarker DLBCL.