Non-Hodgkin Lymphoma Risk and Variants in Genes Controlling Lymphocyte Development

Resource type
Date created
2013
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.
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Published as
Schuetz JM, Daley D, Leach S, Conde L, Berry BR, et al. (2013) Non-Hodgkin Lymphoma Risk and Variants in Genes Controlling Lymphocyte Development. PLoS ONE 8(9): e75170. doi:10.1371/journal.pone.0075170
Publication title
PLoS ONE
Document title
Non-Hodgkin Lymphoma Risk and Variants in Genes Controlling Lymphocyte Development
Date
2013
Volume
8
Issue
9
Publisher DOI
10.1371/journal.pone.0075170
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Copyright is held by the author(s).
Scholarly level
Peer reviewed?
Yes
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nonH.pdf 3.38 MB