title: Effects of ADAMTS14 genetic polymorphism and cigarette smoking on the clinicopathologic development of hepatocellular carcinoma.
abstract: BACKGROUND
  ADAMTS14 is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs), which are proteolytic enzymes with a variety of further ancillary domain in the C-terminal region for substrate specificity and enzyme localization via extracellular matrix association. However, whether ADAMTS14 genetic variants play a role in hepatocellular carcinoma (HCC) susceptibility remains unknown.
  
  
  RESULTS
  Four non-synonymous single-nucleotide polymorphisms (nsSNPs) of the ADAMTS14 gene were examined from 680 controls and 340 patients with HCC. Among 141 HCC patients with smoking behaviour, we found significant associations of the rs12774070 (CC+AA vs CC) and rs61573157 (CT+TT vs CC) variants with a clinical stage of HCC (OR: 2.500 and 2.767; 95% CI: 1.148-5.446 and 1.096-6.483; P = 0.019 and 0.026, respectively) and tumour size (OR: 2.387 and 2.659; 95% CI: 1.098-5.188 and 1.055-6.704; P = 0.026 and 0.034, respectively), but not with lymph node metastasis or other clinical statuses. Moreover, an additional integrated in silico analysis proposed that rs12774070 and rs61573157 affected essential post-translation O-glycosylation site within the 3rd thrombospondin type 1 repeat and a novel proline-rich region embedded within the C-terminal extension, respectively.
  
  
  CONCLUSIONS
  Taken together, our results suggest an involvement of ADAMTS14 SNP rs12774070 and rs61573157 in the liver tumorigenesis and implicate the ADAMTS14 gene polymorphism as a predict factor during the progression of HCC.
authors.affiliation: Department of Gastroenterology and Hepatology, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Sheu
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan.|Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.affiliation: School of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Ying-Erh
authors.initials: YE
authors.lastname: Chou
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Po-Hui
authors.initials: PH
authors.lastname: Wang
authors.affiliation: School of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chao-Bin
authors.initials: CB
authors.lastname: Yeh
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.affiliation: School of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Deptartment of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Hsiang-Lin
authors.initials: HL
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, College of Medicine Sciences and Technology, Chung Shan Medical University, Taichung, Taiwan.|Division of Allergy, Department of Pediatrics, Chung-Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Liu
mesh_terms: D000071096:ADAMTS Proteins / Q000737:chemistry / Q000235:genetics*; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000235:genetics / Q000473:pathology
chemical_list: D000071096:ADAMTS Proteins; C447060:ADAMTS14 protein, human