Genetic Variation in Cell Death Genes and Risk of Non-Hodgkin Lymphoma

Abstract

BackgroundNon-Hodgkin lymphomas are a heterogeneous group of solid tumours that constitute the 5th highest cause of cancer mortality in the United States and Canada. Poor control of cell death in lymphocytes can lead to autoimmune disease or cancer, making genes involved in programmed cell death of lymphocytes logical candidate genes for lymphoma susceptibility.Materials and MethodsWe tested for genetic association with NHL and NHL subtypes, of SNPs in lymphocyte cell death genes using an established population-based study. 17 candidate genes were chosen based on biological function, with 123 SNPs tested. These included tagSNPs from HapMap and novel SNPs discovered by re-sequencing 47 cases in genes for which SNP representation was judged to be low. The main analysis, which estimated odds ratios by fitting data to an additive logistic regression model, used European ancestry samples that passed quality control measures (569 cases and 547 controls). A two-tiered approach for multiple testing correction was used: correction for number of tests within each gene by permutation-based methodology, followed by correction for the number of genes tested using the false discovery rate.ResultsVariant rs928883, near miR-155, showed an association (OR per A-allele: 2.80 [95% CI: 1.63–4.82]; pF = 0.027) with marginal zone lymphoma that is significant after correction for multiple testing.ConclusionsThis is the first reported association between a germline polymorphism at a miRNA locus and lymphoma.

Association of the <b><i>hsa-mir-499</i></b> (rs3746444) Polymorphisms with Gastric Cancer Risk in the Chinese Population

“…miRNAs represent ideal candidates for cancer predisposition loci since small variations in quantity may have an effect on thousands of target mRNAs and result in diverse functional consequences [17]. A few studies have examined the association of SNPs in miRNAs with cancer susceptibility [18,19,20,21,22,23]. However, studies on the association of genetic variants in pre-microRNAs and GC are less common compared with other cancers.…”

Expression Signature of MicroRNA-155 and its Association with Response to Treatment within Different Subtypes of B-Cell Malignancies

“…Also, most of the patients in this research, excluding BL subgroup, were above 40 years old with mean age of 41.8 years. Many previous studies had stated similar data concluding that the majority of B-cell malignancies occur mostly above the age of 50 [23][24][25]. On the other hand, BL is more common in children than in adults [26].…”

Genetic polymorphism at BCL2 as a predictor for rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone efficacy in patients with diffuse large B-cell lymphoma

“…Morteza Bashash, 1,2 Joseph M. Connors, 3,5 Randy D. Gascoyne, 4,5 Barbara Meissner, 5 Johanna M. Schuetz,6 Stephen Leach, 1 Graham W. Slack, 4,5 Brian R. Berry, 7 Howard Hu,…”

“…5 In summary, subjects were patients with NHL without evidence of HIV infection or prior organ transplantation, aged 20-79 at the time of diagnosis, diagnosed between March 2000 and February 2004.…”