A pooled analysis of three studies evaluating genetic variation in innate immunity genes and non-Hodgkin lymphoma risk.
Genetic variation in immune-related genes may play a role in the development of non-Hodgkin lymphoma (NHL). To test the hypothesis that innate immunity polymorphisms may be associated with NHL risk, we genotyped 144 tag single nucleotide polymorphisms (tagSNPs) capturing common genetic variation within 12 innate immunity gene regions in three independent population-based case-control studies (1946 cases and 1808 controls). Gene-based analyses found IL1RN to be associated with NHL risk (minP = 0·03); specifically, IL1RN rs2637988 was associated with an increased risk of NHL (per-allele odds ratio = 1·15, 95% confidence interval = 1·05-1·27; P(trend) = 0·003), which was consistent across study, subtype, and gender. FCGR2A was also associated with a decreased risk of the follicular lymphoma NHL subtype (minP = 0·03). Our findings suggest that genetic variation in IL1RN and FCGR2A may play a role in lymphomagenesis. Given that conflicting results have been reported regarding the association between IL1RN SNPs and NHL risk, a larger number of innate immunity genes with sufficient genomic coverage should be evaluated systematically across many studies.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, MD, USA. hosgoodd@mail.nih.gov
H Dean
HD
Hosgood
Mark P
MP
Purdue
Sophia S
SS
Wang
Tongzhang
T
Zheng
Lindsay M
LM
Morton
Qing
Q
Lan
Idan
I
Menashe
Yawei
Y
Zhang
James R
JR
Cerhan
Andrew
A
Grulich
Wendy
W
Cozen
Meredith
M
Yeager
Theodore R
TR
Holford
Claire M
CM
Vajdic
Scott
S
Davis
Brian
B
Leaderer
Anne
A
Kricker
Maryjean
M
Schenk
Shelia H
SH
Zahm
Nilanjan
N
Chatterjee
Stephen J
SJ
Chanock
Nathaniel
N
Rothman
Patricia
P
Hartge
Bruce
B
Armstrong
D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000276:immunology*; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics
C445323:FCGR2A protein, human; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D009363:Neoplasm Proteins; D017452:Receptors, IgG
Am J Hum Genet. 2002 Feb;70(2):425-34
11791212
Br J Haematol. 2006 Jul;134(2):180-3
16740140
Cancer Res. 2006 Oct 1;66(19):9771-80
17018637
Cancer Epidemiol Biomarkers Prev. 2005 Oct;14(10):2449-53
16214931
Blood. 2006 May 15;107(10):4101-8
16449530
Carcinogenesis. 2007 Mar;28(3):704-12
17056605
Nat Genet. 2009 Dec;41(12):1325-9
19915573
Clin Microbiol Rev. 1996 Oct;9(4):532-62
8894351
Lancet Oncol. 2006 Jan;7(1):27-38
16389181
J Immunol. 1991 Aug 15;147(4):1338-43
1831223
Cancer Epidemiol Biomarkers Prev. 2004 Sep;13(9):1415-21
15342441
PLoS One. 2009;4(4):e5360
19390683
Blood. 1997 Aug 1;90(3):1109-14
9242542
Genet Epidemiol. 2007 Dec;31(8):803-12
17549762
Trends Immunol. 2004 Jun;25(6):280-8
15145317
J Clin Oncol. 1997 Apr;15(4):1587-94
9193357
Scand J Immunol. 1998 Mar;47(3):195-8
9519856
Blood. 1999 Dec 15;94(12):4220-32
10590067
Am J Hum Genet. 2004 Jan;74(1):106-20
14681826
Blood. 2003 Aug 1;102(3):1007-11
12676777
Curr Opin Immunol. 2007 Feb;19(1):1-3
17157490
Ann Hematol. 2005 Jan;84(1):1-12
15480663
Blood. 2007 Apr 15;109(8):3479-88
17185468
Blood. 2007 Jul 15;110(2):695-708
17389762
J Cell Mol Med. 2009 Jul;13(7):1211-20
19538472
Annu Rev Immunol. 1998;16:225-60
9597130
J Exp Med. 1990 Jul 1;172(1):19-25
2141627
Curr Opin Allergy Clin Immunol. 2002 Dec;2(6):495-506
14752332
Cancer Metastasis Rev. 2006 Sep;25(3):315-22
16967326
Hematol Oncol. 1994 Jan-Feb;12(1):15-27
8194840
Eur J Haematol. 2009 Oct;83(4):334-42
19508433
Genet Epidemiol. 2006 Sep;30(6):495-507
16755536
Nat Struct Biol. 1999 May;6(5):437-42
10331870
Clin Infect Dis. 2002 Jan 15;34(2):204-9
11740709
Biomed Pharmacother. 2004 Jun;58(5):286-91
15194164
J Clin Invest. 1996 Mar 1;97(5):1348-54
8636449
Clin Exp Immunol. 2009 Aug;157(2):244-54
19604264
Cancer Causes Control. 2008 Mar;19(2):163-73
18038187
Med Sci Monit. 2005 Feb;11(2):CR75-8
15668636
Am J Epidemiol. 2010 Feb 1;171(3):267-76
20047977
Haematologica. 2004 Aug;89(8):1015-7
15339690