Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma.
Studies have demonstrated that common polymorphisms in Th1 and Th2 cytokine genes can alter gene expression, modulate the balance between Th1/Th2 responsiveness, and influence susceptibility for autoimmune disorders, infectious diseases, and cancer. We analyzed one or more single nucleotide polymorphisms (SNPs) in 20 candidate Th1/Th2 genes in a population-based case-control study of non-Hodgkin lymphoma (NHL; n = 518 cases, 597 controls) among women in Connecticut. SNPs in critical genes, IL4, IL5, IL6, and IL10, were associated with risk for NHL and in some instances with a specific histologic subtype. Analysis of 4 SNPs in the IL10 promoter (-3575T>A, -1082A>G, -819C>T, and -592C>A) revealed that both the AGCC haplotype (odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.21-1.96, P < .001) and the TATA haplotype (OR = 1.37, 95% CI = 1.05-1.79, P = .02) were associated with increased risk for B-cell lymphomas. In contrast, the IL4-1098G allele was associated with increased risk of T-cell lymphomas (OR = 3.84; 95% CI = 1.79-8.22; P < .001). Further, the IL10 and IL4 SNP associations remained significant after adjusting for multiple comparisons. These results suggest that SNPs in Th2 cytokine genes may be associated with risk of NHL.
Lan
Qing
Q
Occupational & Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH/DHHS, MSC 7240, 6120 Executive Blvd, EPS 8109, Bethesda, MD 20892-7240, USA. qingl@mail.nih.gov
Zheng
Tongzhang
T
Rothman
Nathaniel
N
Zhang
Yawei
Y
Wang
Sophia S
SS
Shen
Min
M
Berndt
Sonja I
SI
Zahm
Shelia H
SH
Holford
Theodore R
TR
Leaderer
Brian
B
Yeager
Meredith
M
Welch
Robert
R
Boyle
Peter
P
Zhang
Bing
B
Zou
Kaiyong
K
Zhu
Yong
Y
Chanock
Stephen
S
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002874:Chromosome Mapping; D016207:Cytokines / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020022:Genetic Predisposition to Disease; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044469:Racial Groups; D012189:Retrospective Studies; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D004273:DNA, Neoplasm