Hodgkin lymphoma risk: Role of genetic polymorphisms and gene–gene interactions in DNA repair pathways

Abstract

DNA repair variants may play a potentially important role in an individual’s susceptibility to developing cancer. Numerous studies have reported the association between genetic single nucleotide polymorphisms (SNPs) in DNA repair genes and different types of hematologic cancers. However, to date, the effects of such SNPs on modulating Hodgkin Lymphoma (HL) risk have not yet been investigated. We hypothesized that gene-gene interaction between candidate genes in Direct Reversal, Nucleotide excision repair (NER), Base excision repair (BER) and Double strand break (DSB) pathways may contribute to susceptibility to HL. To test this hypothesis, we conducted a study on 200 HL cases and 220 controls to assess associations between HL risk and 21 functional SNPs in DNA repair genes. We evaluated potential gene-gene interactions and the association of multiple polymorphisms in a chromosome region using a multi-analytic strategy combining logistic regression, multi-factor dimensionality reduction and classification and regression tree approaches. We observed that, in combination, allelic variants in the XPC Ala499Val, NBN Glu185Gln, XRCC3 Thr241Me, XRCC1 Arg194Trp and XRCC1 399Gln polymorphisms modify the risk for developing HL. Moreover, the cumulative genetic risk score revealed a significant trend where the risk for developing HL increases as the number of adverse alleles in BER and DSB genes increase. These findings suggest that DNA repair variants in BER and DSB pathways may play an important role in the development of HL.

DNA Repair Deficiency Associated with Hematological Neoplasms

“…Similarly, XRCC1 Arg399Gln together with XPC Lys/Lys was found to significantly increase HL risk. Similar findings were reported in a recent study that evaluated potential gene-gene interaction between DNA repair genes and their contribution to individual susceptibility to HL (Monroy et al 2011). Polymorphism XRCC1 Arg399Gln was again associated with increased HL risk, as well as polymorphisms XPC Ala499Val, XRCC3 Thr241Met and XRCC1 Arg194Trp.…”

Elevated Serum Levels of sCD30 and IL6 and Detectable IL10 Precede Classical Hodgkin Lymphoma Diagnosis

“…In a study of 41 EBV-positive versus 189 EBV-negative cases at pretreatment, Herling and colleagues (65) reported significantly higher IL-10 levels in the EBV-positive HL patients, while two smaller studies, one based on 22 EBV-positive and 51 EBV-negative cases and the other on only 5 positive and 18 negative cases, reported nonsignificant associations of IL-10 with EBV positivity (10, 66). Genetic polymorphisms in the promoter region of IL10 gene may influence the risk of HL (67–69), possibly by modulating serum IL-10 levels (66). …”

MiR-SNPs as Markers of Toxicity and Clinical Outcome in Hodgkin Lymphoma Patients

“…SNPs in interleukin genes, DNA repair genes and metabolic enzymes have been associated with risk [23], clinical outcome [24], [25] and treatment-related toxicities [26] in HL. miR-SNPs have been related to clinical outcome in several solid tumors [27], [28] and in myeloma[29].…”