Non-Hodgkin lymphoma risk and variants in genes controlling lymphocyte development.

TitleNon-Hodgkin lymphoma risk and variants in genes controlling lymphocyte development.
Publication TypeJournal Article
Year of Publication2013
AuthorsSchuetz, JM, Daley, D, Leach, S, Conde, L, Berry, BR, Gallagher, RP, Connors, JM, Gascoyne, RD, Bracci, PM, Skibola, CF, Spinelli, JJ, Brooks-Wilson, AR
JournalPLoS One
Volume8
Issue9
Paginatione75170
Date Published2013
ISSN1932-6203
KeywordsApoptosis, DNA Repair, DNA-Binding Proteins, European Continental Ancestry Group, Genetic Association Studies, Genotype, Humans, Linkage Disequilibrium, Logistic Models, Lymphocytes, Lymphoma, Non-Hodgkin, Odds Ratio, Polymorphism, Single Nucleotide, Risk Factors
Abstract

Non-Hodgkin lymphomas (NHL) are a heterogeneous group of solid tumours of lymphoid cell origin. Three important aspects of lymphocyte development include immunity and inflammation, DNA repair, and programmed cell death. We have used a previously established case-control study of NHL to ask whether genetic variation in genes involved in these three important processes influences risk of this cancer. 118 genes in these three categories were tagged with single nucleotide polymorphisms (SNPs), which were tested for association with NHL and its subtypes. The main analysis used logistic regression (additive model) to estimate odds ratios in European-ancestry cases and controls. 599 SNPs and 1116 samples (569 cases and 547 controls) passed quality control measures and were included in analyses. Following multiple-testing correction, one SNP in MSH3, a mismatch repair gene, showed an association with diffuse large B-cell lymphoma (OR: 1.91; 95% CI: 1.41-2.59; uncorrected p = 0.00003; corrected p = 0.010). This association was not replicated in an independent European-ancestry sample set of 251 diffuse large B-cell lymphoma cases and 737 controls, indicating this result was likely a false positive. It is likely that moderate sample size, inter-subtype and other genetic heterogeneity, and small true effect sizes account for the lack of replicable findings.

DOI10.1371/journal.pone.0075170
Alternate JournalPLoS ONE
PubMed ID24098683
PubMed Central IDPMC3787098
Grant ListR01CA104682 / CA / NCI NIH HHS / United States
R01CA122663 / CA / NCI NIH HHS / United States
R01CA154643 / CA / NCI NIH HHS / United States
R01CA87014 / CA / NCI NIH HHS / United States
R03CA143947 / CA / NCI NIH HHS / United States
R03CA150037 / CA / NCI NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada