A number of limitations of
A number of limitations of this study should be noted. First, owing to the extremely low incidence of nephroblastoma, the sample size of this case-control was relatively small. Consequently, statistic power of this study was compromised (statistical power no more than 0.307 for significant findings). The significant findings might be chance observations (FPRP values larger than 0.2 at the prior probability level of 0.1). Second, we concentrated on only three BARD1 SNPs. BARD1 gene is highly polymorphic, harboring 4941 SNPs as a minimum (http://www.ncbi.nlm.nih.gov.eleen.top/projects/SNP). Other SNPs that potentially affect the purchase Rimonabant and function of BARD1 should be investigated in the future. Third, we only included Southern Chinese Children in this study. These findings cannot be generalized from one ethnicity to another before validation study. Fourth, in this retrospective study, some important information (e.g., parental exposures) was not available. Due to differences in genetic backgrounds and environmental exposures among the different ethnicities, these findings should be cross-validated with different populations.
Notwithstanding these limitations, our finding did suggest that the rs7585356 G>A polymorphism may confer genetic susceptibility to nephroblastoma. The studied SNPs collectively may increase the risk of nephroblastoma. Moreover, these SNPs appear to be related to the clinical stages of this disease. Well-designed, large, multi-center studies are warranted to strengthen these findings.
Funding Sources This study was supported by the grant of State Clinical Key Specialty Construction Project (Pediatric Surgery) 2013 (No.: GJLCZD1301) and the grant of Clinical Medicine Research and Transformation Center of Brain Injury in Premature Infant in Guangzhou (No.: 520101-2150092). The findings had no role in study design, data collection, data analysis, interpretation, writing of the report.
Conflict of Interest Disclosures
Introduction Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous subtype of non-Hodgkin lymphoma with varied clinical, immunophenotypic and genetic features (SH, 2008). Although the outcome of DLBCL patients has been significantly improved by anti-CD20 monoclonal antibody rituximab combined with induction chemotherapy (mainly as cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]); the lack of remission or early relapse remains a major clinical issue. Therefore, the identification of biomarkers related to therapeutic efficacy, particularly the response to rituximab, may be greatly helpful to conduct risk stratification treatment in DLBCL. In the era of rituximab, in addition to clinical parameters based on International Prognostic Index (IPI) (Sehn et al., 2007), tumor cell of origin (COO) (Alizadeh et al., 2000), as well as BCL-2 and MYC double translocation/expression (Johnson et al., 2012; Green et al., 2012; Horn et al., 2013), are validated as important prognostic indicators of DLBCL. More recently, recurrent gene mutations have been revealed by next-generation sequencing technologies, including those involved in B-cell function (Compagno et al., 2009; Ngo et al., 2011; Davis et al., 2010; Lenz et al., 2008; Kheirallah et al., 2010). B-cell receptors (BCRs) activate NF-κB by harboring receptor mutations in CD79A or CD79B, along with mutations of kinase LYN or effector CARD11 (Rossi et al., 2013). Toll-like receptors (TLRs) recruit protein kinases mainly via adaptor molecule MYD88, also leading to NF-κB activation (Rossi et al., 2013). As an important member of the tumor necrotic factor receptor (TNFR) associated factor (TRAF) protein family, TRAF2 is responsible for TNF-α-mediated modulation of NF-κB (Rossi et al., 2013). Finally, TNFAIP3 mutations resulted in a loss of NF-κB cascade inhibition (Honma et al., 2009). All these genes are closely associated with B-cell function and frequently mutated in DLBCL (Compagno et al., 2009). However, their relationship with lymphoma progression and treatment response warrants further investigation in DLBCL.