Variations in Chromosomes 9 and 6p21.3 with Risk of Non–Hodgkin Lymphoma

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BlankVariations in Chromosomes 9 and 6p21.3 with Risk of Non–Hodgkin Lymphoma

1.. Sophia S. Wang1,

2.. Idan Menashe2,

3.. R. Cerhan3,

4.. Cozen4,

5.. K. Severson5,

6.. 6,

7.. Amy Hutchinson7,

8.. iel Rothman2,

9.. J. Chanock2,7,

10.. Bernstein1,

11.. Hartge2 and

12.. M. Morton2

+ Author Affiliations

1.. Authors' Affiliations:1Division of Cancer Etiology, Department of

Population Sciences, Beckman Research Institute and City of Hope, Duarte,

California; 2Division of Cancer Epidemiology and Genetics, National Cancer

Institute, NIH, DHHS, Rockville, land; 3Division of Epidemiology, College of

Medicine, Mayo Clinic, Rochester, Minnesota; 4Norris Comprehensive Cancer

Center, University of Southern California, Los Angeles, California; 5Department

of Family Medicine and Karmanos Cancer Institute, Wayne State University,

Detroit, Michigan; 6Fred Hutchinson Cancer Research Center and University of

Washington, Seattle, Washington; and 7Core Genotyping Facility, SAIC-Frederick,

Inc., National Cancer Institute, NIH, DHHS, Gaithersburg, land

1.. Corresponding Author:

Sophia S. Wang, Division of Cancer Etiology, Department of Population

Sciences, Beckman Research Institute and City of Hope, 500 Duarte Road, Duarte,

CA 9101. Phone: 626-471-7316; Fax: 626-471-7308. E-mail: sowang@...

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 Cancer Epidemiol Biomarkers Prev; 20(1); 42–9. ©2011 AACR.

Footnotes

a.. Note: Supplementary data for this article are available at Cancer

Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/)