Risk of non-Hodgkin lymphoma in association with germline variation in complement genes

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Abstract

Germline mutations in complement genes have been associated with susceptibility to infections and autoimmune diseases, conditions that are associated with non-Hodgkin lymphoma (NHL) risk. To test the hypothesis that common genetic variation in complement genes affect risk of NHL, we genotyped 167 single nucleotide polymorphisms (SNPs) from 31 genes in 441 NHL cases and 475 controls. Principal components (PC) and haplotype analyses were used for gene-level tests of NHL risk, while individual SNPs were modelled as having a log-additive effect. In gene level PC analyses, C2 (P = 0·023), C5 (P = 0·0032) and C9 (P = 0·020) were associated with NHL risk; haplotype analyses showed similar results, as well as a haplotype association for C7 (P = 0·046). When all four genes were considered simultaneously, only C5 and C9 remained significant (P < 0·05). In SNP level results from these genes, 10 SNPs had a P < 0·05. However, after correcting for multiple testing, only the C5 SNPs rs7026551 (q = 0·015; OR = 1·54, 95% CI 1·21-1·95) and rs2416810 (q = 0·015; OR = 1·57; 95% CI 1·22-2·01), and the C9 SNP rs187875 (q = 0·015; OR = 0·68; 95% 0·56-0·84) remained noteworthy. Associations were similar for the common NHL subtypes. In summary, we provide evidence for a role of genetic variation in complement genes, particularly C5 and C9, and NHL risk.

Original languageEnglish (US)
Pages (from-to)614-623
Number of pages10
JournalBritish Journal of Haematology
Volume145
Issue number5
DOIs
StatePublished - Jun 2009

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Non-Hodgkin's Lymphoma
Single Nucleotide Polymorphism
Genes
Haplotypes
Principal Component Analysis
Germ-Line Mutation
Autoimmune Diseases
Infection

Keywords

  • Complement genes
  • Epidemiology
  • Genetic variation
  • Non-Hodgkin lymphoma

ASJC Scopus subject areas

  • Hematology

Cite this

@article{9fccd46436964bee82c4ce4fa9e3fa2d,
title = "Risk of non-Hodgkin lymphoma in association with germline variation in complement genes",
abstract = "Germline mutations in complement genes have been associated with susceptibility to infections and autoimmune diseases, conditions that are associated with non-Hodgkin lymphoma (NHL) risk. To test the hypothesis that common genetic variation in complement genes affect risk of NHL, we genotyped 167 single nucleotide polymorphisms (SNPs) from 31 genes in 441 NHL cases and 475 controls. Principal components (PC) and haplotype analyses were used for gene-level tests of NHL risk, while individual SNPs were modelled as having a log-additive effect. In gene level PC analyses, C2 (P = 0·023), C5 (P = 0·0032) and C9 (P = 0·020) were associated with NHL risk; haplotype analyses showed similar results, as well as a haplotype association for C7 (P = 0·046). When all four genes were considered simultaneously, only C5 and C9 remained significant (P < 0·05). In SNP level results from these genes, 10 SNPs had a P < 0·05. However, after correcting for multiple testing, only the C5 SNPs rs7026551 (q = 0·015; OR = 1·54, 95{\%} CI 1·21-1·95) and rs2416810 (q = 0·015; OR = 1·57; 95{\%} CI 1·22-2·01), and the C9 SNP rs187875 (q = 0·015; OR = 0·68; 95{\%} 0·56-0·84) remained noteworthy. Associations were similar for the common NHL subtypes. In summary, we provide evidence for a role of genetic variation in complement genes, particularly C5 and C9, and NHL risk.",
keywords = "Complement genes, Epidemiology, Genetic variation, Non-Hodgkin lymphoma",
author = "Cerhan, {James R} and Novak, {Anne J} and Fredericksen, {Zachary S.} and Wang, {Alice H.} and Mark Liebow and Call, {Timothy G.} and Ahmet Dogan and Witzig, {Thomas Elmer} and Ansell, {Stephen Maxted} and Habermann, {Thomas Matthew} and Kay, {Neil Elliot} and Slager, {Susan L}",
year = "2009",
month = "6",
doi = "10.1111/j.1365-2141.2009.07675.x",
language = "English (US)",
volume = "145",
pages = "614--623",
journal = "British Journal of Haematology",
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T1 - Risk of non-Hodgkin lymphoma in association with germline variation in complement genes

AU - Cerhan, James R

AU - Novak, Anne J

AU - Fredericksen, Zachary S.

AU - Wang, Alice H.

AU - Liebow, Mark

AU - Call, Timothy G.

AU - Dogan, Ahmet

AU - Witzig, Thomas Elmer

AU - Ansell, Stephen Maxted

AU - Habermann, Thomas Matthew

AU - Kay, Neil Elliot

AU - Slager, Susan L

PY - 2009/6

Y1 - 2009/6

N2 - Germline mutations in complement genes have been associated with susceptibility to infections and autoimmune diseases, conditions that are associated with non-Hodgkin lymphoma (NHL) risk. To test the hypothesis that common genetic variation in complement genes affect risk of NHL, we genotyped 167 single nucleotide polymorphisms (SNPs) from 31 genes in 441 NHL cases and 475 controls. Principal components (PC) and haplotype analyses were used for gene-level tests of NHL risk, while individual SNPs were modelled as having a log-additive effect. In gene level PC analyses, C2 (P = 0·023), C5 (P = 0·0032) and C9 (P = 0·020) were associated with NHL risk; haplotype analyses showed similar results, as well as a haplotype association for C7 (P = 0·046). When all four genes were considered simultaneously, only C5 and C9 remained significant (P < 0·05). In SNP level results from these genes, 10 SNPs had a P < 0·05. However, after correcting for multiple testing, only the C5 SNPs rs7026551 (q = 0·015; OR = 1·54, 95% CI 1·21-1·95) and rs2416810 (q = 0·015; OR = 1·57; 95% CI 1·22-2·01), and the C9 SNP rs187875 (q = 0·015; OR = 0·68; 95% 0·56-0·84) remained noteworthy. Associations were similar for the common NHL subtypes. In summary, we provide evidence for a role of genetic variation in complement genes, particularly C5 and C9, and NHL risk.

AB - Germline mutations in complement genes have been associated with susceptibility to infections and autoimmune diseases, conditions that are associated with non-Hodgkin lymphoma (NHL) risk. To test the hypothesis that common genetic variation in complement genes affect risk of NHL, we genotyped 167 single nucleotide polymorphisms (SNPs) from 31 genes in 441 NHL cases and 475 controls. Principal components (PC) and haplotype analyses were used for gene-level tests of NHL risk, while individual SNPs were modelled as having a log-additive effect. In gene level PC analyses, C2 (P = 0·023), C5 (P = 0·0032) and C9 (P = 0·020) were associated with NHL risk; haplotype analyses showed similar results, as well as a haplotype association for C7 (P = 0·046). When all four genes were considered simultaneously, only C5 and C9 remained significant (P < 0·05). In SNP level results from these genes, 10 SNPs had a P < 0·05. However, after correcting for multiple testing, only the C5 SNPs rs7026551 (q = 0·015; OR = 1·54, 95% CI 1·21-1·95) and rs2416810 (q = 0·015; OR = 1·57; 95% CI 1·22-2·01), and the C9 SNP rs187875 (q = 0·015; OR = 0·68; 95% 0·56-0·84) remained noteworthy. Associations were similar for the common NHL subtypes. In summary, we provide evidence for a role of genetic variation in complement genes, particularly C5 and C9, and NHL risk.

KW - Complement genes

KW - Epidemiology

KW - Genetic variation

KW - Non-Hodgkin lymphoma

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U2 - 10.1111/j.1365-2141.2009.07675.x

DO - 10.1111/j.1365-2141.2009.07675.x

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