Missense polymorphisms in XIAP-associated factor-1 (XAF1) and risk of papillary thyroid cancer: correlation with clinicopathological features.

X-Linked inhibitor of apoptosis (XIAP)-associated factor-1 (XAF1) antagonizes XIAP-mediated caspase inhibition. XAF1 also serves as a tumor-suppressor gene, and loss of XAF1 expression correlates with tumor progression. This study investigated whether XAF1 missense single-nucleotide polymorphisms (SNPs) are associated with the development of papillary thyroid cancer (PTC) and their clinicopathological features in a Korean population. Eighty-nine cases of PTC and 276 controls were enrolled. Two missense SNPs [rs34195599 (Glu85Gly) and rs2271232 (Arg132His)] in XAF1 were genotyped using direct sequencing. The SNPStats, SNPAnalyzer, Helixtree, and Haploview version 4.2 programs were used to evaluate genetic data. Multiple logistic regression models were used to determine odds ratios (ORs), 95% confidence intervals (CIs), and p-values. Missense SNP rs34195599 was weakly-associated with the development of PTC (p=0.046 in genotypic distributions; p=0.048 in allelic distributions). For the clinicopathological features, rs34195599 was strongly related to multifocality [unifocality (A/G, 1.7%) vs. multifocality (A/G, 16.7%), OR=11.44, 95% CI=1.27-103.26, p=0.015 in genotypic distributions] [unifocality (G, 0.8%) vs. multifocality (G, 8.3%), OR=10.64, 95% CI=1.21-93.23, p=0.017 in allelic distributions] and location [one lobe (A/G, 1.6%) vs. both lobes (A/G, 19.2%), OR=15.63, 95% CI=1.62-150.46, p=0.008 in genotypic distributions] [one lobe (G, 0.8%) vs. both lobes (G, 9.6%), OR=13.30, 95% CI=1.51-116.82, p=0.009 in allelic distributions]. Our data suggest that the G allele of rs34195599 of XAF1 may be a risk factor for the clinicopathological features of PTC, especially for multifocality and location (both lobes).