title: Missense polymorphisms in XIAP-associated factor-1 (XAF1) and risk of papillary thyroid cancer: correlation with clinicopathological features.
abstract: 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).
authors: Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul, Korea.
authors: Su Kang
authors: SK
authors: Kim
authors: Hae Jeong
authors: HJ
authors: Park
authors: Hosik
authors: H
authors: Seok
authors: Hye Sook
authors: HS
authors: Jeon
authors: Jong Woo
authors: JW
authors: Kim
authors: Joo-Ho
authors: JH
authors: Chung
authors: Kee Hwan
authors: KH
authors: Kwon
authors: Seung-Hoon
authors: SH
authors: Woo
authors: Byoung Wook
authors: BW
authors: Lee
authors: Hyung Hwan
authors: HH
authors: Baik
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C417551:XAF1 protein, human
keywords: Clinicopathological features; XAF1; papillary thyroid cancer; polymorphism