Polymorphisms in complement system genes and risk of non-Hodgkin lymphoma

Bryan A. Bassig; Tongzhang Zheng; Yawei Zhang; Sonja I. Berndt; Theodore R. Holford; H. Dean Hosgood; Wei Hu; Brian Leaderer; Meredith Yeager; Idan Menashe; Peter Boyle; Jun Xu; Kaiyong Zou; Yong Zhu; Stephen Chanock; Nathaniel Rothman; Qing Lan

doi:10.1002/em.21675

Polymorphisms in complement system genes and risk of non-Hodgkin lymphoma

Bryan A. Bassig, Tongzhang Zheng, Yawei Zhang, Sonja I. Berndt, Theodore R. Holford, H. Dean Hosgood, Wei Hu, Brian Leaderer, Meredith Yeager, Idan Menashe, Peter Boyle, Jun Xu, Kaiyong Zou, Yong Zhu, Stephen Chanock, Nathaniel Rothman, Qing Lan

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

14 Scopus citations

Abstract

The complement system plays an important role in inflammatory and immune responses, and recent evidence has suggested that it may also play a role in lymphomagenesis. We evaluated the association between genetic variation in complement system genes and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study conducted among women in Connecticut. Tag SNPs in 30 complement genes were genotyped in 432 Caucasian incident cases and 494 frequency-matched controls. A gene-based analysis that adjusted for the number of tag SNPs genotyped in each gene showed a significant association with NHL overall (P = 0.04) as well as with diffuse large B-cell lymphoma (DLBCL) (P = 0.01) for the C1RL gene. A SNP-based analysis showed that a C>T base substitution for C1RL rs3813729 (odds ratio (OR) _CT = 0.60, 95% confidence interval (CI) = 0.42-0.87, P _trend = 0.0062) was associated with a decreased risk of overall NHL, as well as for DLBCL (OR _CT = 0.39, 95% CI = 0.20-0.73; P _trend = 0.0034). Additionally, SNPs (C2 rs497309, A>C and C3 rs344550, G>C) in two complement genes were positively associated with marginal zone lymphoma (MZL) and C1QG was associated with CLL/SLL, but these results were based on a limited number of cases. Our results suggest a potential role of the complement system in susceptibility to NHL; however, our results should be viewed as exploratory and further replication is needed to clarify these preliminary findings.

Original language	English (US)
Pages (from-to)	145-151
Number of pages	7
Journal	Environmental and Molecular Mutagenesis
Volume	53
Issue number	2
DOIs	https://doi.org/10.1002/em.21675
State	Published - Mar 2012
Externally published	Yes

Keywords

C1RL
Innate immunity
Lymphoma
SNP

ASJC Scopus subject areas

Epidemiology
Genetics(clinical)
Health, Toxicology and Mutagenesis

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10.1002/em.21675

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Bassig, B. A., Zheng, T., Zhang, Y., Berndt, S. I., Holford, T. R., Hosgood, H. D., Hu, W., Leaderer, B., Yeager, M., Menashe, I., Boyle, P., Xu, J., Zou, K., Zhu, Y., Chanock, S., Rothman, N., & Lan, Q. (2012). Polymorphisms in complement system genes and risk of non-Hodgkin lymphoma. Environmental and Molecular Mutagenesis, 53(2), 145-151. https://doi.org/10.1002/em.21675

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title = "Polymorphisms in complement system genes and risk of non-Hodgkin lymphoma",

abstract = "The complement system plays an important role in inflammatory and immune responses, and recent evidence has suggested that it may also play a role in lymphomagenesis. We evaluated the association between genetic variation in complement system genes and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study conducted among women in Connecticut. Tag SNPs in 30 complement genes were genotyped in 432 Caucasian incident cases and 494 frequency-matched controls. A gene-based analysis that adjusted for the number of tag SNPs genotyped in each gene showed a significant association with NHL overall (P = 0.04) as well as with diffuse large B-cell lymphoma (DLBCL) (P = 0.01) for the C1RL gene. A SNP-based analysis showed that a C>T base substitution for C1RL rs3813729 (odds ratio (OR) CT = 0.60, 95% confidence interval (CI) = 0.42-0.87, P trend = 0.0062) was associated with a decreased risk of overall NHL, as well as for DLBCL (OR CT = 0.39, 95% CI = 0.20-0.73; P trend = 0.0034). Additionally, SNPs (C2 rs497309, A>C and C3 rs344550, G>C) in two complement genes were positively associated with marginal zone lymphoma (MZL) and C1QG was associated with CLL/SLL, but these results were based on a limited number of cases. Our results suggest a potential role of the complement system in susceptibility to NHL; however, our results should be viewed as exploratory and further replication is needed to clarify these preliminary findings.",

keywords = "C1RL, Innate immunity, Lymphoma, SNP",

author = "Bassig, {Bryan A.} and Tongzhang Zheng and Yawei Zhang and Berndt, {Sonja I.} and Holford, {Theodore R.} and Hosgood, {H. Dean} and Wei Hu and Brian Leaderer and Meredith Yeager and Idan Menashe and Peter Boyle and Jun Xu and Kaiyong Zou and Yong Zhu and Stephen Chanock and Nathaniel Rothman and Qing Lan",

year = "2012",

month = mar,

doi = "10.1002/em.21675",

language = "English (US)",

volume = "53",

pages = "145--151",

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AU - Bassig, Bryan A.

AU - Zheng, Tongzhang

AU - Zhang, Yawei

AU - Berndt, Sonja I.

AU - Holford, Theodore R.

AU - Hosgood, H. Dean

AU - Hu, Wei

AU - Leaderer, Brian

AU - Yeager, Meredith

AU - Menashe, Idan

AU - Boyle, Peter

AU - Xu, Jun

AU - Zou, Kaiyong

AU - Zhu, Yong

AU - Chanock, Stephen

AU - Rothman, Nathaniel

AU - Lan, Qing

PY - 2012/3

Y1 - 2012/3

N2 - The complement system plays an important role in inflammatory and immune responses, and recent evidence has suggested that it may also play a role in lymphomagenesis. We evaluated the association between genetic variation in complement system genes and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study conducted among women in Connecticut. Tag SNPs in 30 complement genes were genotyped in 432 Caucasian incident cases and 494 frequency-matched controls. A gene-based analysis that adjusted for the number of tag SNPs genotyped in each gene showed a significant association with NHL overall (P = 0.04) as well as with diffuse large B-cell lymphoma (DLBCL) (P = 0.01) for the C1RL gene. A SNP-based analysis showed that a C>T base substitution for C1RL rs3813729 (odds ratio (OR) CT = 0.60, 95% confidence interval (CI) = 0.42-0.87, P trend = 0.0062) was associated with a decreased risk of overall NHL, as well as for DLBCL (OR CT = 0.39, 95% CI = 0.20-0.73; P trend = 0.0034). Additionally, SNPs (C2 rs497309, A>C and C3 rs344550, G>C) in two complement genes were positively associated with marginal zone lymphoma (MZL) and C1QG was associated with CLL/SLL, but these results were based on a limited number of cases. Our results suggest a potential role of the complement system in susceptibility to NHL; however, our results should be viewed as exploratory and further replication is needed to clarify these preliminary findings.

AB - The complement system plays an important role in inflammatory and immune responses, and recent evidence has suggested that it may also play a role in lymphomagenesis. We evaluated the association between genetic variation in complement system genes and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study conducted among women in Connecticut. Tag SNPs in 30 complement genes were genotyped in 432 Caucasian incident cases and 494 frequency-matched controls. A gene-based analysis that adjusted for the number of tag SNPs genotyped in each gene showed a significant association with NHL overall (P = 0.04) as well as with diffuse large B-cell lymphoma (DLBCL) (P = 0.01) for the C1RL gene. A SNP-based analysis showed that a C>T base substitution for C1RL rs3813729 (odds ratio (OR) CT = 0.60, 95% confidence interval (CI) = 0.42-0.87, P trend = 0.0062) was associated with a decreased risk of overall NHL, as well as for DLBCL (OR CT = 0.39, 95% CI = 0.20-0.73; P trend = 0.0034). Additionally, SNPs (C2 rs497309, A>C and C3 rs344550, G>C) in two complement genes were positively associated with marginal zone lymphoma (MZL) and C1QG was associated with CLL/SLL, but these results were based on a limited number of cases. Our results suggest a potential role of the complement system in susceptibility to NHL; however, our results should be viewed as exploratory and further replication is needed to clarify these preliminary findings.

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KW - Lymphoma

KW - SNP

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Polymorphisms in complement system genes and risk of non-Hodgkin lymphoma

Abstract

Keywords

ASJC Scopus subject areas

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