NEW YORK (GenomeWeb) – A new study suggests some of the same genetic variants contribute to thyroid cancer risk in European and Korean populations, though additional, population-specific susceptibility variants turned up in Korea, where the disease is particularly prevalent.
In an effort to understand thyroid cancer risk in the Korean population, researchers from Korea and the US performed genome-wide association and replication analyses involving nearly 1,110 individuals with differentiated thyroid cancer — either papillary thyroid cancer or follicular thyroid cancer subtypes — and almost 8,900 unaffected controls, searching for variants that were overrepresented in individuals with the condition.
The team subsequently validated suspicious variants using a combination of clinical data and expression quantitative trait locus profiles, uncovering variants with apparent ties to thyroid cancer at 10 loci: four loci linked to thyroid cancer risk in prior studies and half a dozen risky loci not reported in the past in studies of individuals of European ancestry. The results appeared online today in Nature Communications.
"Our findings provide deeper insight into the genetic contribution to thyroid cancer in different populations," wrote senior authors Jong-II Kim and Young Joo Park, at the Seoul National University, and the National Cancer Center's Eun Kyung Lee, as well as their co-authors.
Although 12 or more thyroid cancer risk loci have been reported in European population GWAS, the team noted, only a handful of the same loci have been linked to thyroid cancer susceptibility in studies of individuals from China or Japan, or individuals from specific parts of Europe, such as Poland or the UK, hinting at the possibility of variable risk contributors from one population to the next.
For their own two-stage GWAS, the researchers compared patterns at more than 3.5 million directly genotyped or imputed SNPs in 410 Korean individuals with papillary thyroid cancer, 60 individuals with follicular thyroid cancer, and 8,279 unaffected individuals from Korea who were enrolled through population studies.
The team initially identified two genome-wide significant loci for each thyroid cancer subtype, along with dozens of suspicious SNPs. After validation testing in another 587 papillary thyroid cancer patients, 28 individuals with follicular thyroid cancer, and 605 unaffected individuals, the group replicated 13 SNPs at 10 loci across differentiated thyroid cancer in general and two SNPs that were specific to follicular thyroid cancer.
When they added in eQTL patterns gleaned from SNP and gene expression data for dozens of thyroid tumor or normal thyroid tissues, the researchers saw overlap between thyroid cancer risk and eQTL variants at four loci, including a site near the neuregulin 1-coding gene NRG1 that had the most significant susceptibility association.
"Although we did not demonstrate the direct effects of the increased expression of NRG1 on tumor aggressiveness," the authors wrote, "we could postulate a possibility that the increased expression of NRG1 in the thyroid tissue, which is associated with identified variants, might influence the development or progression of thyroid cancer."
The investigators also considered similarities and difference in variants associated with thyroid cancer risk in the Korean population with those implicated in past European GWAS and delved into loci showing specific ties to one of the thyroid cancer subtypes.