Polymorphisms in pattern-recognition genes in the innate immunity system and risk of non-Hodgkin lymphoma.
The pattern-recognition pathway plays an important role in infection recognition and immune responses, and previous studies have suggested an association between genetic variation in innate immunity genes and non-Hodgkin lymphoma (NHL). We evaluated NHL risk associated with genetic variation in pattern-recognition genes using data from a case-control study of NHL conducted in Connecticut women. Single nucleotide polymorphisms (SNPs) in 27 pattern-recognition genes were genotyped in 432 Caucasian incident NHL cases and 494 frequency-matched controls. Unconditional logistic regression was used to compute odds ratios (ORs) for NHL and common NHL subtypes in relation to individual SNPs and haplotypes. A gene-based analysis that adjusted for the number of tagSNPs genotyped in each gene showed a significant association with overall NHL for the MBP gene (P = 0.028), with the diffuse large B-cell lymphoma (DLBCL) subtype for the MASP2 gene (P = 0.011), and with the follicular lymphoma (FL) subtype for DEFB126 (P = 0.041). A SNP-based analysis showed that MBP rs8094402 was associated with decreased risks of overall NHL (allele risk OR = 0.72, P-trend = 0.0018), DLBCL (allele risk OR = 0.72, P-trend = 0.036), and FL (allele risk OR = 0.67, P-trend = 0.021), while MASP2 rs12711521 was associated with a decreased risk of DLBCL (allele risk OR = 0.57, P-trend = 0.0042). We also observed an increased risk of FL for DEFB126 rs6054706 (allele risk OR = 1.39, P-trend = 0.033). Our results suggest that genetic variation in pattern-recognition genes is associated with the risk of NHL or specific NHL subtypes, but these preliminary findings require replication in larger studies.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland 20892-7240, USA. wei.hu@nih.gov
Wei
W
Hu
Bryan A
BA
Bassig
Jun
J
Xu
Tongzhang
T
Zheng
Yawei
Y
Zhang
Sonja I
SI
Berndt
Theodore R
TR
Holford
H Dean
HD
Hosgood
Brian
B
Leaderer
Meredith
M
Yeager
Idan
I
Menashe
Peter
P
Boyle
Kaiyong
K
Zou
Yong
Y
Zhu
Stephen
S
Chanock
Qing
Q
Lan
Nathaniel
N
Rothman
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003237:Connecticut; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D016015:Logistic Models; D008224:Lymphoma, Follicular / Q000235:genetics / Q000276:immunology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics*; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051192:Receptors, Pattern Recognition / Q000235:genetics; D044465:White People / Q000235:genetics; D055815:Young Adult; D023083:beta-Defensins / Q000235:genetics*
C426184:DEFB126 protein, human; C499048:MBP protein, human; D004676:Myelin Basic Protein; D051192:Receptors, Pattern Recognition; D023083:beta-Defensins; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases