Oncotarget published "Fine–mapping of two differentiated thyroid carcinoma susceptibility loci at 2q35 and 8p12 in Europeans, Melanesians and Polynesians" which reported that Genome-wide association studies identified mainly four DTC susceptibility loci at 9q22.33, 14q13.3, 2q35 and 8p12. Here we performed fine-mapping of the 2q35 and 8p12 loci in the population of the EPITHYR consortium that includes Europeans, Melanesians and Polynesians to identify likely causal variants for DTC risk.
At 2q35, the authors highlighted rs16857609 located in DIRC3. This SNP has a high probability of causality in the three populations, and a significant association in Europeans.
It is also associated with expression of DIRC3 and of the nearby gene IGFBP5 in thyroid tumour cells.
At 8p12, they identified rs7844425 which was significantly associated with DTC in Europeans and rs2439304, which was highlighted by the colocalization analysis but only moderately associated with DTC in their dataset.
Hence, this Oncotarget study identified novel variants at 2q35 and 8p12 to be prioritized for further functional studies.
Dr. Thérèse Truong from The University Paris-Saclay said, "Thyroid cancer (TC) is the most common endocrine malignancy."
"Thyroid cancer (TC) is the most common endocrine malignancy."
Six previous genome-wide association studies of DTC conducted in European populations and a GWAS conducted in the Asian population allowed the identification of several DTC susceptibility loci, with the strongest associations being reported at 9q22.33, 14q13.3, 2q35 and 8p12. Recently, a meta-analysis including 3,001 DTC cases and 287,500 controls of European descent confirmed these findings and yielded five additional loci associated to DTC at 1q42.2, 3q26.2, 5q22.1, 10q24.33, 15q22.33 that were not replicated yet.
At locus 2q35, several other variants were also highlighted by GWAS to be associated with DTC in populations of European ancestry.
Rs6759952 was reported in GWAS conducted on 3648 DTC cases and 4,224 controls from Italy, while a recent meta-analysis of GWAS reported the strongest association with variant rs11693806 at this locus.
Figure 4: Forest plot of subgroup analyses for rs7844425 stratifying on study, sex, age group, histology and size of carcinoma in Europeans, and stratifying on population group in the entire dataset. Result for the imputed SNP rs7844425 in NRG1 at 8p12 (Effect allele (A) frequency in Europeans: 0.34). EAF: effect allele frequency; EUR: Europeans; MEL: Melanesians; POL: Polynesians; Het: heterogeneity.
In Korea, a GWAS identified two additional SNPs at 2q35, namely rs12990503 and rs1549738, associated with DTC risk.
The Korean GWAS highlighted two other DTC risk variants, namely rs6996585 and rs12542743, with rs6996585 being moderately correlated with the GWAS SNP rs2439302.
The Truong Research Team concluded in their Oncotarget Research Output, "we confirmed the previously associated SNPs in Europeans and in Asians at loci 2q35 and 8p12, and our fine-mapping approach identified new potential causal SNPs at each locus (rs16857609 at locus 2q35, rs7844425 and rs2439304 at locus 8p12) to be prioritized for functional studies."
DOI - https://doi.org/10.18632/oncotarget.27888
Full text - https://www.oncotarget.com/article/27888/text/
Correspondence to - Thérèse Truong - [email protected]
Keywords - thyroid cancer, cancer genetics, case-control study, fine-mapping study, single nucleotide polymorphism
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