Genetic variation in Th1/Th2 pathway genes and risk of non-Hodgkin lymphoma: A pooled analysis of three population-based case-control studies

Qing Lan; Sophia S. Wang; Idan Menashe; Bruce Armstrong; Yawei Zhang; Patricia Hartge; Mark P. Purdue; Theodore R. Holford; Lindsay M. Morton; Anne Kricker; James R. Cerhan; Andrew Grulich; Wendy Cozen; Shelia H. Zahm; Meredith Yeager; Claire M. Vajdic; Maryjean Schenk; Brian Leaderer; Jeff Yuenger; Richard K. Severson; Nilanjan Chatterjee; Stephen J. Chanock; Tongzhang Zheng; Nathaniel Rothman

doi:10.1111/j.1365-2141.2010.08424.x

Genetic variation in Th1/Th2 pathway genes and risk of non-Hodgkin lymphoma: A pooled analysis of three population-based case-control studies

Qing Lan, Sophia S. Wang, Idan Menashe, Bruce Armstrong, Yawei Zhang, Patricia Hartge, Mark P. Purdue, Theodore R. Holford, Lindsay M. Morton, Anne Kricker, James R. Cerhan, Andrew Grulich, Wendy Cozen, Shelia H. Zahm, Meredith Yeager, Claire M. Vajdic, Maryjean Schenk, Brian Leaderer, Jeff Yuenger, Richard K. SeversonNilanjan Chatterjee, Stephen J. Chanock, Tongzhang Zheng, Nathaniel Rothman

Research output: Contribution to journal › Article › peer-review

Abstract

The balance between T-helper 1 (Th1) and T-helper 2 (Th2) activity is critical in lymphoid cell development and differentiation. Immune dysfunction underlies lymphomagenesis, so an alteration in the regulation of key Th1/Th2 cytokines may lead to the development of non-Hodgkin lymphoma (NHL). To study the impact of polymorphisms in Th1/Th2 cytokines on NHL risk, we analyzed 145 tag single nucleotide polymorphisms (SNPs) in 17 Th1/Th2 cytokine and related genes in three population-based case-control studies (1946 cases and 1808 controls). Logistic regression was used to compute odds ratios (OR) for NHL and four major NHL subtypes in relation to tag SNP genotypes and haplotypes. A gene-based analysis adjusting for the number of tag SNPs genotyped in each gene showed significant associations with risk of NHL combined and one or more NHL subtypes for Th1 (IL12A and IL12RB1) and Th2 (IL4, IL10RB, and IL18) genes. The strongest association was for rs485497 in IL12A, which plays a central role in bridging the cellular and humoral pathways of innate resistance and antigen-specific adaptive immune responses (allele risk OR=1·17; P(trend)=0·00099). This SNP was also associated specifically with risk of follicular lymphoma (allele risk OR=1·26; P(trend)=0·0012). These findings suggest that genetic variation in Th1/Th2 cytokine genes may contribute to lymphomagenesis. Published 2011. This article is a US Government work and is in the public domain in the USA.

Original language	American English
Pages (from-to)	341-350
Number of pages	10
Journal	British Journal of Haematology
Volume	153
Issue number	3
DOIs	https://doi.org/10.1111/j.1365-2141.2010.08424.x
State	Published - 1 May 2011
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Case-control study
Immunogenetics
Non-Hodgkin lymphoma
Single nucleotide polymorphisms

All Science Journal Classification (ASJC) codes

Hematology

Access to Document

10.1111/j.1365-2141.2010.08424.x

Cite this

Lan, Q., Wang, S. S., Menashe, I., Armstrong, B., Zhang, Y., Hartge, P., Purdue, M. P., Holford, T. R., Morton, L. M., Kricker, A., Cerhan, J. R., Grulich, A., Cozen, W., Zahm, S. H., Yeager, M., Vajdic, C. M., Schenk, M., Leaderer, B., Yuenger, J., ... Rothman, N. (2011). Genetic variation in Th1/Th2 pathway genes and risk of non-Hodgkin lymphoma: A pooled analysis of three population-based case-control studies. British Journal of Haematology, 153(3), 341-350. https://doi.org/10.1111/j.1365-2141.2010.08424.x

@article{a191439856b0405688be91b557a7f578,

title = "Genetic variation in Th1/Th2 pathway genes and risk of non-Hodgkin lymphoma: A pooled analysis of three population-based case-control studies",

abstract = "The balance between T-helper 1 (Th1) and T-helper 2 (Th2) activity is critical in lymphoid cell development and differentiation. Immune dysfunction underlies lymphomagenesis, so an alteration in the regulation of key Th1/Th2 cytokines may lead to the development of non-Hodgkin lymphoma (NHL). To study the impact of polymorphisms in Th1/Th2 cytokines on NHL risk, we analyzed 145 tag single nucleotide polymorphisms (SNPs) in 17 Th1/Th2 cytokine and related genes in three population-based case-control studies (1946 cases and 1808 controls). Logistic regression was used to compute odds ratios (OR) for NHL and four major NHL subtypes in relation to tag SNP genotypes and haplotypes. A gene-based analysis adjusting for the number of tag SNPs genotyped in each gene showed significant associations with risk of NHL combined and one or more NHL subtypes for Th1 (IL12A and IL12RB1) and Th2 (IL4, IL10RB, and IL18) genes. The strongest association was for rs485497 in IL12A, which plays a central role in bridging the cellular and humoral pathways of innate resistance and antigen-specific adaptive immune responses (allele risk OR=1·17; P(trend)=0·00099). This SNP was also associated specifically with risk of follicular lymphoma (allele risk OR=1·26; P(trend)=0·0012). These findings suggest that genetic variation in Th1/Th2 cytokine genes may contribute to lymphomagenesis. Published 2011. This article is a US Government work and is in the public domain in the USA.",

keywords = "Case-control study, Immunogenetics, Non-Hodgkin lymphoma, Single nucleotide polymorphisms",

author = "Qing Lan and Wang, {Sophia S.} and Idan Menashe and Bruce Armstrong and Yawei Zhang and Patricia Hartge and Purdue, {Mark P.} and Holford, {Theodore R.} and Morton, {Lindsay M.} and Anne Kricker and Cerhan, {James R.} and Andrew Grulich and Wendy Cozen and Zahm, {Shelia H.} and Meredith Yeager and Vajdic, {Claire M.} and Maryjean Schenk and Brian Leaderer and Jeff Yuenger and Severson, {Richard K.} and Nilanjan Chatterjee and Chanock, {Stephen J.} and Tongzhang Zheng and Nathaniel Rothman",

year = "2011",

month = may,

day = "1",

doi = "10.1111/j.1365-2141.2010.08424.x",

language = "American English",

volume = "153",

pages = "341--350",

journal = "British Journal of Haematology",

issn = "0007-1048",

publisher = "John Wiley and Sons Inc.",

number = "3",

}

Lan, Q, Wang, SS, Menashe, I, Armstrong, B, Zhang, Y, Hartge, P, Purdue, MP, Holford, TR, Morton, LM, Kricker, A, Cerhan, JR, Grulich, A, Cozen, W, Zahm, SH, Yeager, M, Vajdic, CM, Schenk, M, Leaderer, B, Yuenger, J, Severson, RK, Chatterjee, N, Chanock, SJ, Zheng, T & Rothman, N 2011, 'Genetic variation in Th1/Th2 pathway genes and risk of non-Hodgkin lymphoma: A pooled analysis of three population-based case-control studies', British Journal of Haematology, vol. 153, no. 3, pp. 341-350. https://doi.org/10.1111/j.1365-2141.2010.08424.x

TY - JOUR

T1 - Genetic variation in Th1/Th2 pathway genes and risk of non-Hodgkin lymphoma

T2 - A pooled analysis of three population-based case-control studies

AU - Lan, Qing

AU - Wang, Sophia S.

AU - Menashe, Idan

AU - Armstrong, Bruce

AU - Zhang, Yawei

AU - Hartge, Patricia

AU - Purdue, Mark P.

AU - Holford, Theodore R.

AU - Morton, Lindsay M.

AU - Kricker, Anne

AU - Cerhan, James R.

AU - Grulich, Andrew

AU - Cozen, Wendy

AU - Zahm, Shelia H.

AU - Yeager, Meredith

AU - Vajdic, Claire M.

AU - Schenk, Maryjean

AU - Leaderer, Brian

AU - Yuenger, Jeff

AU - Severson, Richard K.

AU - Chatterjee, Nilanjan

AU - Chanock, Stephen J.

AU - Zheng, Tongzhang

AU - Rothman, Nathaniel

PY - 2011/5/1

Y1 - 2011/5/1

N2 - The balance between T-helper 1 (Th1) and T-helper 2 (Th2) activity is critical in lymphoid cell development and differentiation. Immune dysfunction underlies lymphomagenesis, so an alteration in the regulation of key Th1/Th2 cytokines may lead to the development of non-Hodgkin lymphoma (NHL). To study the impact of polymorphisms in Th1/Th2 cytokines on NHL risk, we analyzed 145 tag single nucleotide polymorphisms (SNPs) in 17 Th1/Th2 cytokine and related genes in three population-based case-control studies (1946 cases and 1808 controls). Logistic regression was used to compute odds ratios (OR) for NHL and four major NHL subtypes in relation to tag SNP genotypes and haplotypes. A gene-based analysis adjusting for the number of tag SNPs genotyped in each gene showed significant associations with risk of NHL combined and one or more NHL subtypes for Th1 (IL12A and IL12RB1) and Th2 (IL4, IL10RB, and IL18) genes. The strongest association was for rs485497 in IL12A, which plays a central role in bridging the cellular and humoral pathways of innate resistance and antigen-specific adaptive immune responses (allele risk OR=1·17; P(trend)=0·00099). This SNP was also associated specifically with risk of follicular lymphoma (allele risk OR=1·26; P(trend)=0·0012). These findings suggest that genetic variation in Th1/Th2 cytokine genes may contribute to lymphomagenesis. Published 2011. This article is a US Government work and is in the public domain in the USA.

AB - The balance between T-helper 1 (Th1) and T-helper 2 (Th2) activity is critical in lymphoid cell development and differentiation. Immune dysfunction underlies lymphomagenesis, so an alteration in the regulation of key Th1/Th2 cytokines may lead to the development of non-Hodgkin lymphoma (NHL). To study the impact of polymorphisms in Th1/Th2 cytokines on NHL risk, we analyzed 145 tag single nucleotide polymorphisms (SNPs) in 17 Th1/Th2 cytokine and related genes in three population-based case-control studies (1946 cases and 1808 controls). Logistic regression was used to compute odds ratios (OR) for NHL and four major NHL subtypes in relation to tag SNP genotypes and haplotypes. A gene-based analysis adjusting for the number of tag SNPs genotyped in each gene showed significant associations with risk of NHL combined and one or more NHL subtypes for Th1 (IL12A and IL12RB1) and Th2 (IL4, IL10RB, and IL18) genes. The strongest association was for rs485497 in IL12A, which plays a central role in bridging the cellular and humoral pathways of innate resistance and antigen-specific adaptive immune responses (allele risk OR=1·17; P(trend)=0·00099). This SNP was also associated specifically with risk of follicular lymphoma (allele risk OR=1·26; P(trend)=0·0012). These findings suggest that genetic variation in Th1/Th2 cytokine genes may contribute to lymphomagenesis. Published 2011. This article is a US Government work and is in the public domain in the USA.

KW - Case-control study

KW - Immunogenetics

KW - Non-Hodgkin lymphoma

KW - Single nucleotide polymorphisms

UR - http://www.scopus.com/inward/record.url?scp=79954421370&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2141.2010.08424.x

DO - 10.1111/j.1365-2141.2010.08424.x

M3 - Article

C2 - 21418175

SN - 0007-1048

VL - 153

SP - 341

EP - 350

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 3

ER -

Genetic variation in Th1/Th2 pathway genes and risk of non-Hodgkin lymphoma: A pooled analysis of three population-based case-control studies

Abstract

UN SDGs

Keywords

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this