Autor: |
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 |
Jazyk: |
angličtina |
Rok vydání: |
2013 |
Předmět: |
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Zdroj: |
PLoS ONE, Vol 8, Iss 3, p e57243 (2013) |
Druh dokumentu: |
article |
ISSN: |
1932-6203 |
DOI: |
10.1371/journal.pone.0057243 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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