A Study About The Hereditary Susceptibility Of Papillary Thyroid Carcinoma

Part Ⅰ Confirmation of papillary thyroid cancer susceptibility loci identified by Genome-Wide Association StudiesBackground Five single nucleotide polymorphisms (SNPs) associated with thyroid cancer of European population have been reported by two GWAS (Genome-wide association study):rs965513(9q22.33), rs944289(14q13.3), rs116909374(14q13.3), rs966423(2q35) and rs2439302(8pl2). Only the first two SNPs were replicated in independent populations and none were confirmed in Chinese populations.Methods This study genotyped five SNPs in845papillary thyroid carcinoma (PTC),503benign thyroid tumor (BN) and1005controls in Chinese populations by SNaPshot multiplex single nucleotide extension system.Results Significant associations were detected between PTC and rs944289(P=8.007e-11), rs965513(P=1.013e-4), rs966423(P=1.688e-3) and rs2439302(P=1.096e-4) in dominant model. No SNPs were dectected for rs116909374in Chinese population. The PTC risk is increasing with increased accumulative number of risk alleles of individuals (P=5.929e-13). The Odds Ratio of PTC for six risk allele carriers (1.4%of control population) was23.587compared with individuals who are non-risk homozygous (1.0%of control population, with0risk allele). There were no individuals who are homozygous at the four SNPs (8alleles carrier) and only three PTC cases were7risk alleles carrier (0.4%of PTC cases). An association between14q13.3SNP rs944289T and benign thyroid tumor was also found (P=0.0070).Conclusions Four candidate loci, rs965513(9q22.33), rs944289(14q13.3), rs966423(2q35) and rs2439302(8p12), indentified by GWAS for PTC risk were confirmed in Chinese population. The PTC risk of accumulative risk allele carriers is increasing with the accumulative number of risk alleles. Part Ⅱ A study about the associations of genetic loci within CAPZB gene with thyroid tumor susceptibility and serum TSH concentrationsBackground A GWAS (genome-wide association study) has reported two independent genetic loci associated with goiter risk in Caucasian population:the lead SNP rs10917468upstream of CAPZB, and the lead SNP rs12045440in the intron of CAPZB. And rs10917469, which is in strong linkage disequilibrium of rs10917468(r2=0.60), was found to be associated with serum TSH concentration in another GWAS of Caucasian population. No further studies revealed an association of the two genetic loci with serum TSH concentration in independent populations.Method We genotyped SNPs rs12045440and rs10917468in870papillary thyroid carcinoma (PTC),513benign thyroid tumor (BN) and1244controls in Chinese populations by SNaPshot multiplex single nucleotide extension system. The PTC and BN patients received preoperative serum thyroid function measurements.Results A significant association was detected between rs12045440and serum TSH concentrations in thyroid tumor patients (p=0.001). The mean concentration of the wide-type TT genotype of rs12045440was0.34mIU/L lower than that of the alternative homozygote GG genotype in thyroid tumor patients (mean.±SD.1.91±1.62vs.2.25±1.65mIU/L). The difference of mean serum TSH level in different genotypes of rs12045440was still significant in BN group after adjustment of relevant covariates (p=0.003), but was marginally significant in PTC cases (p=0.115). No significant association of rs10917468with TSH levels was found in PTC/BN groups, and the distributions of the two SNPs in PTC/BN and controls were not statistically significant (rs10917468:p=0.989, BN vs. control; p=0.896, PTC vs. control.rs12045440:p=0.458, BN vs. control; p=0.180, PTC vs. control.) Conclusions The SNP rs12045440within intron1of CAPZB was associated with serum TSH concentrations in Chinese thyroid tumor patients, especially in thyroid benign tumor cases.