Table 1. Major Results of Genome-Wide Association Study of Differentiated Thyroid Cancer in the Population of European Ancestrya.
| Chromosome | SNP (RA/OA) | Annotation | SNP function | Nearest gene | Risk allele frequency | Allelic ORb | Replicatedc |
|---|---|---|---|---|---|---|---|
| 2q35 | rs966423 (C/T) | Intron | NE | DIRC3 | 0.41 | 1.28 | No |
| rs11693806 (C/G) | Exon, non-coding | NE | 0.32 | 1.43 | No | ||
| 8p12 | rs2439302 (G/C) | Intron 1 | Risk allele decreases NRG1 expression | NRG1 | 0.48 | 1.32 | Yes |
| 9q22.33 | rs965513 (A/G) | Intergenic | Enhancer element involved in the regulation of PTCSC2 and FOXE1 expression | FOXE1, PTCSC2 | 0.40 | 1.70 | Yes |
| rs1867277 (A/G)d | 5′UTR | Risk allele regulates FOXE1 transcription through the differential recruitment of USF1/USF2 transcription factors | FOXE1 | 0.52 | 1.49 | Yes | |
| 14q13.3 | rs944289 (T/C) | Non-coding, promoter | Risk allele decreases promoter activation PTCSC3, by weakening the binding affinity of the NKX2-1 p42 C/EBPα and β | PTCSC3, NKX2-1 | 0.60 | 1.35 | Yes |
| rs116909374 (T/C) | Intergenic | NE | MBIP1 | 0.04 | 1.71 | Absente | |
| Recently discovered SNPs | |||||||
| 1q42.2 | rs12129938 (A/G) | Intron 1 | NE | PCNXL2 | 0.80 | 1.32 | No |
| 3q26.2 | rs6793295 (T/C) | Missense variant (p.Ser249Gly) | NE | LRRC34 | 0.76 | 1.23 | No |
| 5p15.33 | rs10069690 (T/C) | Intron 4 | NE | TERT | 0.28 | 1.20 | No |
| 5q22.1 | rs73227498 (A/T) | Intergenic | NE | EPB41L4A | 0.87 | 1.37 | No |
| 10q24.33 | rs7902587 (T/C) | Intergenic | NE | OBFC1 | 0.11 | 1.41 | Absent |
| 15q22.33 | rs2289261 (C/G) | Intron | NE | SMAD3 | 0.68 | 1.23 | No |
SNP, single-nucleotide polymorphism; RA, risk allele; OA, other allele; OR, odds ratio; NE, not established; DIRC3, disrupted in renal carcinoma 3; NRG1, neuregulin 1; PTCSC2, papillary thyroid carcinoma susceptibility candidate 2; FOXE1, forkhead box E1; 5′UTR, 5′ untranslated region; USF1/USF2, upstream transcription factor 1/2; C/EBP, CCAAT (cytosine-cytosine-adenosine-adenosine-thymidine)/enhancer binding protein; PTCSC3, papillary thyroid carcinoma susceptibility candidate 3; NKX2-1, NK2 homeobox 1; MBIP1, MAP3K12 binding inhibitory protein 1; PCNXL2, pecanex homolog 2; LRRC34, leucine rich repeat containing 34; TERT, telomerase reverse transcriptase; EPB41L4A, erythrocyte membrane protein band 4.1 like 4A; OBFC1, STN1, CST complex subunit; SMAD3, SMAD family member 3.
aData according to the results from [24]; bAllelic effect size in terms of odds ratio; cReplication studies in Asian population(s); dData from the target gene study ref [16]; eZero allelic frequency in the Asian populations.