Title |
Common Single Nucleotide Polymorphisms in Genes Related to Immune Function and Risk of Papillary Thyroid Cancer
|
---|---|
Published in |
PLOS ONE, March 2013
|
DOI | 10.1371/journal.pone.0057243 |
Pubmed ID | |
Authors |
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 |
Abstract |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 45 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 9 | 20% |
Student > Ph. D. Student | 8 | 18% |
Student > Bachelor | 4 | 9% |
Student > Master | 4 | 9% |
Professor | 3 | 7% |
Other | 6 | 13% |
Unknown | 11 | 24% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 11 | 24% |
Biochemistry, Genetics and Molecular Biology | 10 | 22% |
Agricultural and Biological Sciences | 8 | 18% |
Immunology and Microbiology | 1 | 2% |
Computer Science | 1 | 2% |
Other | 2 | 4% |
Unknown | 12 | 27% |