[48], one year after ABVD treatment, the surviving cells from HL patients presented NCCA but not CCA [48], while in the study of Salas et al. affects hematopoietic and germ stem cells leading to long-term genotoxic effects and azoospermia, while ABVD chemotherapy affects transiently sperm cells, with most of the patients showing recovery of spermatogenesis. Both regimens have long-term effects in somatic cells, presenting nonclonal chromosomal aberrations and genomic Palmitic acid chaos in a fraction of noncancerous cells. This is a source of karyotypic heterogeneity that could eventually generate a more stable population acquiring clonal chromosomal aberrations and leading towards the development of a new cancer. (12q31), (9q34), (19p13) and, recently, or (19p13.3), associated also with pre-B cell acute lymphoblastic leukemia. Loss of heterozygosity analysis revealed that 80% of primary cHL cases displayed monoallelic losses of 16q21-q23, 6q25 (78%), 12p12 (75%), 3q26 (67%), and 2p23 (57%), however the implicated genes remain to be studied [7,8]. The precise etiology of HL is unknown, HL behaves as a multifactorial entity, presenting genetic and environmental risk factors. Genetic susceptibility has F2R been evidenced by the existence of family aggregation. The study of families with two or more affected members with HL has allowed the detection of genes predisposing to HL. Rotunno et al. in 2016 [9] studied, by whole exome sequencing, 65 families with recurrent HL and found in two families, the only recurrent mutation found until now, a nonsynonymous c.3193G>A change in the gene (kinase insert domain receptor) also known as VEGFR2 (vascular endothelial growth factor receptor 2), since most of the identified variants are private for each affected family. In addition, twin studies have shown that the risk for HL is 100 times higher in identical twins than in fraternal twins, indicating that in these families, the genetic component is stronger Palmitic acid than environmental factors [2,9]. Recognized environmental risk factors involved in HL include the presence of the -herpes virus, autoimmune disease and immunosuppression. A high percentage ~40C90% of HL patients are positive for Epstein Bar Virus (EBV). Although the involvement of viral Palmitic acid infection in the pathogenesis of HL is controversial, certain studies have shown that the activity of some EBV proteins contributes to the development and maintenance of HRS tumor cells. EBV virus may be in lytic or latent state; the lytic infection produces a large quantity of virions that kill the host cell, whereas the latent infection produces a reduced amount of viral proteins that retain the virus as an episome or integrated into the chromosomes, this latent state keeps the host cell alive and has been associated to cell growth and transformation through activation of different latent membrane proteins LMP1, LMP2A, and LMP2B, as well as EBNA1, EBER RNAs, and BART microRNAs. Functional studies of LMP1 and LMP2A have shown that the first activates NF-B, Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase pathways and the latter participates in the inhibition of apoptosis and evasion of the immune response. EBNA1 and LMP1 promote genomic instability, a well-known requirement for malignant transformation and microRNAs participate in immune evasion [2,8]. HL cells show telomere dysfunction; in EBV positive HL patients LMP1 viral protein induces inhibition and dysfunction of TRF2 (shelterins group) leading to telomere shortening in HL lymph nodes. Short telomeres Palmitic acid induce chromosomal abnormalities, promoting telomere fusion which generate dicentric chromosomes, breakage-fusion-bridge cycles, abnormal chromosomal segregation, aneuploidy, and nonclonal structural chromosomal aberrations; all of Palmitic acid these abnormalities are present in HRS cells [10]. Peripheral blood lymphocytes in HL patients also present telomere erosion. Mkacher et al. [11] showed that telomeric length was significantly shorter in HL patients without therapy as compared with healthy donors (8.3 vs. 11.7 kb length); five years after receiving Chemotherapy (CT), telomeres decreased in length but not significantly (7.64 kb length), while HL patients in complete remission recover their telomeric length (9.7 kb), suggesting that telomere length may be a risk factor for the occurrence of secondary cancers and diseases in long-term survivors [11]. 3. Genotoxicity of the Anticancer Treatment in Hodgkin Lymphoma Chemotherapy..