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Variations in chromosomes 9 and 6p21.3 with risk of non-Hodgkin lymphoma.


ABSTRACT: BACKGROUND:There is growing evidence linking genetic variations to non-Hodgkin lymphoma (NHL) etiology. To complement ongoing agnostic approaches for identifying susceptibility genes, we evaluated 488 candidate gene regions and their relation to risk for NHL and NHL subtypes. METHODS:We genotyped 6,679 tag single nucleotide polymorphisms (SNPs) in 947 cases and 826 population-based controls from a multicenter U.S. case-control study. Gene-level summary of associations were obtained by computing the minimum P value ("minP test") on the basis of 10,000 permutations. We used logistic regression to evaluate the association between genotypes and haplotypes with NHL. For NHL subtypes, we conducted polytomous multivariate unconditional logistic regression (adjusted for sex, race, age). We calculated P-trends under the codominant model for each SNP. RESULTS:Fourteen gene regions were associated with NHL (P < 0.01). The most significant SNP associated with NHL maps to the SYK gene (rs2991216, P-trend = 0.00005). The three most significant gene regions were on chromosome 6p21.3 (RING1/RXRB; AIF1; BAT4). Accordingly, SNPs in RING1/RXRB (rs2855429), AIF1 (rs2857597), and BAT4 (rs3115667) were associated with NHL (P-trends ? 0.0002) and both diffuse large B-cell and follicular lymphomas (P-trends < 0.05). CONCLUSIONS:Our results suggest potential importance for SYK on chromosome 9 with NHL etiology. Our results further implicate 6p21.3 gene variants, supporting the need for full characterization of this chromosomal region in relation to lymphomagenesis. IMPACT:Gene variants on chromosome 9 may represent a new region of interesting for NHL etiology. The independence of the reported variants in 6p21.3 from implicated variants (TNF/HLA) supports the need to confirm causal variants in this region.

SUBMITTER: Wang SS 

PROVIDER: S-EPMC3817834 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Variations in chromosomes 9 and 6p21.3 with risk of non-Hodgkin lymphoma.

Wang Sophia S SS   Menashe Idan I   Cerhan James R JR   Cozen Wendy W   Severson Richard K RK   Davis Scott S   Hutchinson Amy A   Rothman Nathaniel N   Chanock Stephen J SJ   Bernstein Leslie L   Hartge Patricia P   Morton Lindsay M LM  

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20101210 1


<h4>Background</h4>There is growing evidence linking genetic variations to non-Hodgkin lymphoma (NHL) etiology. To complement ongoing agnostic approaches for identifying susceptibility genes, we evaluated 488 candidate gene regions and their relation to risk for NHL and NHL subtypes.<h4>Methods</h4>We genotyped 6,679 tag single nucleotide polymorphisms (SNPs) in 947 cases and 826 population-based controls from a multicenter U.S. case-control study. Gene-level summary of associations were obtaine  ...[more]

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