A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma

Mark P. Purdue; Qing Lan; Sophia S. Wang; Anne Kricker; Idan Menashe; Tong Zhang Zheng; Patricia Hartge; Andrew E. Grulich; Yawei Zhang; Lindsay M. Morton; Claire M. Vajdic; Theodore R. Holford; Richard K. Severson; Brian P. Leaderer; James R. Cerhan; Meredith Yeager; Wendy Cozen; Kevin Jacobs; Scott Davis; Nathaniel Rothman; Stephen J. Chanock; Nilanjan Chatterjee; Bruce K. Armstrong

doi:10.1093/carcin/bgn262

A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma

Mark P. Purdue, Qing Lan, Sophia S. Wang, Anne Kricker, Idan Menashe, Tong Zhang Zheng, Patricia Hartge, Andrew E. Grulich, Yawei Zhang, Lindsay M. Morton, Claire M. Vajdic, Theodore R. Holford, Richard K. Severson, Brian P. Leaderer, James R. Cerhan, Meredith Yeager, Wendy Cozen, Kevin Jacobs, Scott Davis, Nathaniel RothmanStephen J. Chanock, Nilanjan Chatterjee, Bruce K. Armstrong

Quantitative Health Sciences

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

68 Scopus citations

Abstract

Toll-like receptors (TLRs) may influence the development of non-Hodgkin lymphoma (NHL) given their important roles in recognizing microbial pathogens and stimulating multiple immune pathways. We conducted an investigation of TLR gene variants in a pooled analysis including three population-based case-control studies of NHL (1946 cases and 1808 controls). Thirty-six tag single-nucleotide polymorphisms (SNPs) in TLR2, TLR4 and the TLR10-TLR1-TLR6 gene cluster were genotyped. Two TLR10-TLR1-TLR6 variants in moderate linkage disequilibrium were significantly associated with NHL: rs10008492 [odds ratio for CT genotype (OR_CT) 1.12, 95% confidence interval (CI) 0.97-1.30; OR_TT 1.40, 95% CI 1.15-1.71; P_trend = 0.001] and rs4833103 (OR_AC 0.75, 95% CI 0.64-0.88; OR_AA 0.74, 95% CI 0.62-0.90; P_trend = 0.002; P_dominant = 0.0002). Associations with these SNPs were consistent across all the three studies and did not appreciably differ by histologic subtype. We found little evidence of association between TLR2 variation and all NHL, although the rare variant rs3804100 was significantly associated with marginal zone lymphoma (MZL), both overall (OR_CT/CC 1.89, 95% CI 1.27-2.81; P_dominant = 0.002) and in two of the three studies. No associations with TLR4 variants were observed. This pooled analysis provides strong evidence that variation in the TLR10-TLR1-TLR6 region is associated with NHL risk and suggests that TLR2 variants may influence susceptibility to MZL.

Original language	English (US)
Pages (from-to)	275-281
Number of pages	7
Journal	Carcinogenesis
Volume	30
Issue number	2
DOIs	https://doi.org/10.1093/carcin/bgn262
State	Published - 2009

ASJC Scopus subject areas

Cancer Research

Access to Document

10.1093/carcin/bgn262

Cite this

Purdue, M. P., Lan, Q., Wang, S. S., Kricker, A., Menashe, I., Zheng, T. Z., Hartge, P., Grulich, A. E., Zhang, Y., Morton, L. M., Vajdic, C. M., Holford, T. R., Severson, R. K., Leaderer, B. P., Cerhan, J. R., Yeager, M., Cozen, W., Jacobs, K., Davis, S., ... Armstrong, B. K. (2009). A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma. Carcinogenesis, 30(2), 275-281. https://doi.org/10.1093/carcin/bgn262

Purdue, MP, Lan, Q, Wang, SS, Kricker, A, Menashe, I, Zheng, TZ, Hartge, P, Grulich, AE, Zhang, Y, Morton, LM, Vajdic, CM, Holford, TR, Severson, RK, Leaderer, BP, Cerhan, JR, Yeager, M, Cozen, W, Jacobs, K, Davis, S, Rothman, N, Chanock, SJ, Chatterjee, N & Armstrong, BK 2009, 'A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma', Carcinogenesis, vol. 30, no. 2, pp. 275-281. https://doi.org/10.1093/carcin/bgn262

@article{3284319f76ab44508e6b3841ab0eb624,

title = "A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma",

abstract = "Toll-like receptors (TLRs) may influence the development of non-Hodgkin lymphoma (NHL) given their important roles in recognizing microbial pathogens and stimulating multiple immune pathways. We conducted an investigation of TLR gene variants in a pooled analysis including three population-based case-control studies of NHL (1946 cases and 1808 controls). Thirty-six tag single-nucleotide polymorphisms (SNPs) in TLR2, TLR4 and the TLR10-TLR1-TLR6 gene cluster were genotyped. Two TLR10-TLR1-TLR6 variants in moderate linkage disequilibrium were significantly associated with NHL: rs10008492 [odds ratio for CT genotype (ORCT) 1.12, 95% confidence interval (CI) 0.97-1.30; ORTT 1.40, 95% CI 1.15-1.71; Ptrend = 0.001] and rs4833103 (ORAC 0.75, 95% CI 0.64-0.88; ORAA 0.74, 95% CI 0.62-0.90; Ptrend = 0.002; Pdominant = 0.0002). Associations with these SNPs were consistent across all the three studies and did not appreciably differ by histologic subtype. We found little evidence of association between TLR2 variation and all NHL, although the rare variant rs3804100 was significantly associated with marginal zone lymphoma (MZL), both overall (ORCT/CC 1.89, 95% CI 1.27-2.81; Pdominant = 0.002) and in two of the three studies. No associations with TLR4 variants were observed. This pooled analysis provides strong evidence that variation in the TLR10-TLR1-TLR6 region is associated with NHL risk and suggests that TLR2 variants may influence susceptibility to MZL.",

author = "Purdue, {Mark P.} and Qing Lan and Wang, {Sophia S.} and Anne Kricker and Idan Menashe and Zheng, {Tong Zhang} and Patricia Hartge and Grulich, {Andrew E.} and Yawei Zhang and Morton, {Lindsay M.} and Vajdic, {Claire M.} and Holford, {Theodore R.} and Severson, {Richard K.} and Leaderer, {Brian P.} and Cerhan, {James R.} and Meredith Yeager and Wendy Cozen and Kevin Jacobs and Scott Davis and Nathaniel Rothman and Chanock, {Stephen J.} and Nilanjan Chatterjee and Armstrong, {Bruce K.}",

note = "Funding Information: Intramural Research Program of the National Institutes of Health (National Cancer Institute) to all genotyping and statistical analysis for this work and NCI-SEER study; Public Health Service (N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105) to NCI-SEER study; National Cancer Institute National Institutes of Health grant (CA62006) to Connecticut study; National Health and Medical Research Council of Australia (990920 to B.K.A), Cancer Council New South Wales (NSW), University of Sydney Medical Foundation to NSW study; NSW Health Department to NSW Central Cancer Registry.",

year = "2009",

doi = "10.1093/carcin/bgn262",

language = "English (US)",

volume = "30",

pages = "275--281",

journal = "Carcinogenesis",

issn = "0143-3334",

publisher = "Oxford University Press",

number = "2",

}

TY - JOUR

T1 - A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma

AU - Purdue, Mark P.

AU - Lan, Qing

AU - Wang, Sophia S.

AU - Kricker, Anne

AU - Menashe, Idan

AU - Zheng, Tong Zhang

AU - Hartge, Patricia

AU - Grulich, Andrew E.

AU - Zhang, Yawei

AU - Morton, Lindsay M.

AU - Vajdic, Claire M.

AU - Holford, Theodore R.

AU - Severson, Richard K.

AU - Leaderer, Brian P.

AU - Cerhan, James R.

AU - Yeager, Meredith

AU - Cozen, Wendy

AU - Jacobs, Kevin

AU - Davis, Scott

AU - Rothman, Nathaniel

AU - Chanock, Stephen J.

AU - Chatterjee, Nilanjan

AU - Armstrong, Bruce K.

N1 - Funding Information: Intramural Research Program of the National Institutes of Health (National Cancer Institute) to all genotyping and statistical analysis for this work and NCI-SEER study; Public Health Service (N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105) to NCI-SEER study; National Cancer Institute National Institutes of Health grant (CA62006) to Connecticut study; National Health and Medical Research Council of Australia (990920 to B.K.A), Cancer Council New South Wales (NSW), University of Sydney Medical Foundation to NSW study; NSW Health Department to NSW Central Cancer Registry.

PY - 2009

Y1 - 2009

N2 - Toll-like receptors (TLRs) may influence the development of non-Hodgkin lymphoma (NHL) given their important roles in recognizing microbial pathogens and stimulating multiple immune pathways. We conducted an investigation of TLR gene variants in a pooled analysis including three population-based case-control studies of NHL (1946 cases and 1808 controls). Thirty-six tag single-nucleotide polymorphisms (SNPs) in TLR2, TLR4 and the TLR10-TLR1-TLR6 gene cluster were genotyped. Two TLR10-TLR1-TLR6 variants in moderate linkage disequilibrium were significantly associated with NHL: rs10008492 [odds ratio for CT genotype (ORCT) 1.12, 95% confidence interval (CI) 0.97-1.30; ORTT 1.40, 95% CI 1.15-1.71; Ptrend = 0.001] and rs4833103 (ORAC 0.75, 95% CI 0.64-0.88; ORAA 0.74, 95% CI 0.62-0.90; Ptrend = 0.002; Pdominant = 0.0002). Associations with these SNPs were consistent across all the three studies and did not appreciably differ by histologic subtype. We found little evidence of association between TLR2 variation and all NHL, although the rare variant rs3804100 was significantly associated with marginal zone lymphoma (MZL), both overall (ORCT/CC 1.89, 95% CI 1.27-2.81; Pdominant = 0.002) and in two of the three studies. No associations with TLR4 variants were observed. This pooled analysis provides strong evidence that variation in the TLR10-TLR1-TLR6 region is associated with NHL risk and suggests that TLR2 variants may influence susceptibility to MZL.

AB - Toll-like receptors (TLRs) may influence the development of non-Hodgkin lymphoma (NHL) given their important roles in recognizing microbial pathogens and stimulating multiple immune pathways. We conducted an investigation of TLR gene variants in a pooled analysis including three population-based case-control studies of NHL (1946 cases and 1808 controls). Thirty-six tag single-nucleotide polymorphisms (SNPs) in TLR2, TLR4 and the TLR10-TLR1-TLR6 gene cluster were genotyped. Two TLR10-TLR1-TLR6 variants in moderate linkage disequilibrium were significantly associated with NHL: rs10008492 [odds ratio for CT genotype (ORCT) 1.12, 95% confidence interval (CI) 0.97-1.30; ORTT 1.40, 95% CI 1.15-1.71; Ptrend = 0.001] and rs4833103 (ORAC 0.75, 95% CI 0.64-0.88; ORAA 0.74, 95% CI 0.62-0.90; Ptrend = 0.002; Pdominant = 0.0002). Associations with these SNPs were consistent across all the three studies and did not appreciably differ by histologic subtype. We found little evidence of association between TLR2 variation and all NHL, although the rare variant rs3804100 was significantly associated with marginal zone lymphoma (MZL), both overall (ORCT/CC 1.89, 95% CI 1.27-2.81; Pdominant = 0.002) and in two of the three studies. No associations with TLR4 variants were observed. This pooled analysis provides strong evidence that variation in the TLR10-TLR1-TLR6 region is associated with NHL risk and suggests that TLR2 variants may influence susceptibility to MZL.

UR - http://www.scopus.com/inward/record.url?scp=60149086960&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=60149086960&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgn262

DO - 10.1093/carcin/bgn262

M3 - Article

C2 - 19029192

AN - SCOPUS:60149086960

SN - 0143-3334

VL - 30

SP - 275

EP - 281

JO - Carcinogenesis

JF - Carcinogenesis

IS - 2

ER -

A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this