Common single nucleotide polymorphisms in genes related to immune function and risk of papillary thyroid cancer.
Accumulating evidence suggests that alterations in immune function may be important in the etiology of papillary thyroid cancer (PTC). To identify genetic markers in immune-related pathways, we evaluated 3,985 tag single nucleotide polymorphisms (SNPs) in 230 candidate gene regions (adhesion-extrava...
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doaj-c495525e47ef4525bf50b5a7208fc6352020-11-25T01:26:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5724310.1371/journal.pone.0057243Common single nucleotide polymorphisms in genes related to immune function and risk of papillary thyroid cancer.Alina V BrennerGila NetaErich M SturgisRuth M PfeifferAmy HutchinsonMeredith YeagerLi XuCindy ZhouWilliam WheelerMargaret A TuckerStephen J ChanockAlice J SigurdsonAccumulating evidence suggests that alterations in immune function may be important in the etiology of papillary thyroid cancer (PTC). To identify genetic markers in immune-related pathways, we evaluated 3,985 tag single nucleotide polymorphisms (SNPs) in 230 candidate gene regions (adhesion-extravasation-migration, arachidonic acid metabolism/eicosanoid signaling, complement and coagulation cascade, cytokine signaling, innate pathogen detection and antimicrobials, leukocyte signaling, TNF/NF-kB pathway or other) in a case-control study of 344 PTC cases and 452 controls. We used logistic regression models to estimate odds ratios (OR) and calculate one degree of freedom P values of linear trend (P(SNP-trend) ) for the association between genotype (common homozygous, heterozygous, variant homozygous) and risk of PTC. To correct for multiple comparisons, we applied the false discovery rate method (FDR). Gene region- and pathway-level associations (P(Region) and P(Pathway)) were assessed by combining individual P(SNP-trend) values using the adaptive rank truncated product method. Two SNPs (rs6115, rs6112) in the SERPINA5 gene were significantly associated with risk of PTC (P(SNP-FDR)/P(SNP-trend)= 0.02/6×10(-6) and P(SNP-FDR)/P(SNP-trend)= 0.04/2×10(-5), respectively). These associations were independent of a history of autoimmune thyroiditis (OR = 6.4; 95% confidence interval: 3.0-13.4). At the gene region level, SERPINA5 was suggestively associated with risk of PTC (P(Region-FDR)/P(Region)= 0.07/0.0003). Overall, the complement and coagulation cascade pathway was the most significant pathway (P(Pathway)= 0.02) associated with PTC risk largely due to the strong effect of SERPINA5. Our results require replication but suggest that the SERPINA5 gene, which codes for the protein C inhibitor involved in many biological processes including inflammation, may be a new susceptibility locus for PTC.http://europepmc.org/articles/PMC3592848?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alina V Brenner Gila Neta Erich M Sturgis Ruth M Pfeiffer Amy Hutchinson Meredith Yeager Li Xu Cindy Zhou William Wheeler Margaret A Tucker Stephen J Chanock Alice J Sigurdson |
spellingShingle |
Alina V Brenner Gila Neta Erich M Sturgis Ruth M Pfeiffer Amy Hutchinson Meredith Yeager Li Xu Cindy Zhou William Wheeler Margaret A Tucker Stephen J Chanock Alice J Sigurdson Common single nucleotide polymorphisms in genes related to immune function and risk of papillary thyroid cancer. PLoS ONE |
author_facet |
Alina V Brenner Gila Neta Erich M Sturgis Ruth M Pfeiffer Amy Hutchinson Meredith Yeager Li Xu Cindy Zhou William Wheeler Margaret A Tucker Stephen J Chanock Alice J Sigurdson |
author_sort |
Alina V Brenner |
title |
Common single nucleotide polymorphisms in genes related to immune function and risk of papillary thyroid cancer. |
title_short |
Common single nucleotide polymorphisms in genes related to immune function and risk of papillary thyroid cancer. |
title_full |
Common single nucleotide polymorphisms in genes related to immune function and risk of papillary thyroid cancer. |
title_fullStr |
Common single nucleotide polymorphisms in genes related to immune function and risk of papillary thyroid cancer. |
title_full_unstemmed |
Common single nucleotide polymorphisms in genes related to immune function and risk of papillary thyroid cancer. |
title_sort |
common single nucleotide polymorphisms in genes related to immune function and risk of papillary thyroid cancer. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Accumulating evidence suggests that alterations in immune function may be important in the etiology of papillary thyroid cancer (PTC). To identify genetic markers in immune-related pathways, we evaluated 3,985 tag single nucleotide polymorphisms (SNPs) in 230 candidate gene regions (adhesion-extravasation-migration, arachidonic acid metabolism/eicosanoid signaling, complement and coagulation cascade, cytokine signaling, innate pathogen detection and antimicrobials, leukocyte signaling, TNF/NF-kB pathway or other) in a case-control study of 344 PTC cases and 452 controls. We used logistic regression models to estimate odds ratios (OR) and calculate one degree of freedom P values of linear trend (P(SNP-trend) ) for the association between genotype (common homozygous, heterozygous, variant homozygous) and risk of PTC. To correct for multiple comparisons, we applied the false discovery rate method (FDR). Gene region- and pathway-level associations (P(Region) and P(Pathway)) were assessed by combining individual P(SNP-trend) values using the adaptive rank truncated product method. Two SNPs (rs6115, rs6112) in the SERPINA5 gene were significantly associated with risk of PTC (P(SNP-FDR)/P(SNP-trend)= 0.02/6×10(-6) and P(SNP-FDR)/P(SNP-trend)= 0.04/2×10(-5), respectively). These associations were independent of a history of autoimmune thyroiditis (OR = 6.4; 95% confidence interval: 3.0-13.4). At the gene region level, SERPINA5 was suggestively associated with risk of PTC (P(Region-FDR)/P(Region)= 0.07/0.0003). Overall, the complement and coagulation cascade pathway was the most significant pathway (P(Pathway)= 0.02) associated with PTC risk largely due to the strong effect of SERPINA5. Our results require replication but suggest that the SERPINA5 gene, which codes for the protein C inhibitor involved in many biological processes including inflammation, may be a new susceptibility locus for PTC. |
url |
http://europepmc.org/articles/PMC3592848?pdf=render |
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