Age at diagnosis and gender modify the risk of 9q22 and 14q13 polymorphisms for papillary thyroid carcinoma.

Introduction: Papillary thyroid cancer (PTC) shows familial occurrence, and some susceptibility single nucleotide polymorphisms (SNPs) have been identified in FOXE1 and near the NKX2-1 locus. The aim of our study was to analyse the association of PTC risk with SNPs in FOXE1 (rs965513, rs1867277, rs1443434) and near the NKX2-1 locus (rs944289) in a Polish population, and, in the second step, the interaction between SNPs and patient-related factors (age at diagnosis and gender). Material and methods: A total of 2243 DNA samples from PTC patients and 1160 controls were included in the study. The SNP analysis was performed with the allelic discrimination technique. Results: There were significant associations of all SNPs with PTC (rs965513 odds ratio [OR] = 1.72, p = 8 x 10(-7); rs1867277 OR = 1.59, p = 1 x 10(-6); rs1443434 OR = 1.53, p = 1 x 10(-5); rs944289 OR = 1.52, p = 4 x 10(-5)). Logistic regression analysis revealed an increased PTC risk in the interaction of rs944289 with age at diagnosis (OR = 1.01 per year, p = 6 x 10(-4)) and a decreased PTC risk in the interaction of male gender with the GGT FOXE1 protective haplotype (OR = 0.69, p = 0.01). Conclusions: The association between PTC and all analysed SNPs was confirmed. It was also shown that patient-related factors modify the predisposition to PTC by increasing the risk for rs944289 per year of age, and by enhancing the protective effect of the FOXE1 GGT haplotype in men.