title: Genomic single nucleotide polymorphisms in the offspring of gastric cancer patients predispose to spasmolytic polypeptide-expressing metaplasia after H. pylori infection.
abstract: BACKGROUND
  Gastric cancer exhibits familial clustering, and gastric cancer familial relatives (GCF) tend to present with corpus-predominant gastritis and precancerous lesions as SPEM or IM after H. pylori infection. The study determined whether the children of gastric cancer patients (GCA) had genomic single nucleotide polymorphisms (SNPs) predisposed to the gastric precancerous lesions as spasmolytic polypeptide-expressing metaplasia (SPEM) or intestinal metaplasia (IM).
  
  
  RESULTS
  There were 389 family relatives of 193 non-cardiac GCA and 173 duodenal ulcer patients (DU), received blood sampling for DNA collection. The differences of the risk alleles of SNPs in the ITGA5, ITGB1, IL-10, COX-2, RUNX3, and TFF2 genes were compared between 195 children of GCA and 143 DU. The children of GCA had higher allele frequencies of ITGA5-1160 T-carrier (P = 0.006, OR[95% CI] = 2.2[1.2-4]), ITGB1-1949 A-carrier (P = 0.047; OR[95% CI] = 2.8[1.4-5.3]), ITGB1 + 31804 C-carrier (P = 0.013; OR[95% CI] = 4.7[1.7-13.0]), IL-10-592 AA (P = 0.014; OR[95% CI] = 2.3[1.4-4.0]) and COX-2-1195 G-carrier (P = 0.019; OR[95% CI] = 1.7[0.9-3.2]) than DU. The combined genotype with ITGA5-1160/ITGB1-1949/ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA was more prevalent in the children of GCA than in DU (P < 1×10(-4)), and predisposed with a 5.3-fold risk of getting SPEM in the H. pylori-infected children of GCA (P = 0.016). Such risk of getting SPEM increased to 112 folds, if combined with RUNX3 + 492/TFF2-308 as A-carrier/CC in this limited study scale (P = 1×10(-4)).
  
  
  CONCLUSIONS
  The SNPs of ITGA5-1160/ITGB1-1949/ ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA, or more specific to combine RUNX3 + 492/TFF2-308 as A-carrier/CC shall be host factor predisposing to gastric cancer during H. pylori infection, and serve as marker to identify high-risk subjects for H. pylori eradication.
authors.affiliation: Departments of Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. dr.aching@msa.hinet.net.|Department of Internal Medicine, National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan, 70428, Taiwan. dr.aching@msa.hinet.net.|Department of Internal Medicine, Tainan Hospital, Department of Health, Executive Yuan, Tainan, Taiwan. dr.aching@msa.hinet.net.
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Tsai
authors.affiliation: Departments of Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. p9885221@yahoo.com.tw.
authors.forename: Wei-Hsin
authors.initials: WH
authors.lastname: Hsiao
authors.affiliation: Departments of Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. shlin922@mail.ncku.edu.tw.
authors.forename: Sheng-Hsiang
authors.initials: SH
authors.lastname: Lin
authors.affiliation: Departments of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. hbyang@tyh.com.tw.|Department of Pathology, Ton-Yen General Hospital, Hsin-Chu, Taiwan. hbyang@tyh.com.tw.
authors.forename: Hsiao-Bai
authors.initials: HB
authors.lastname: Yang
authors.affiliation: Departments of Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. teishuki@mail.ncku.edu.tw.|Department of Internal Medicine, National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan, 70428, Taiwan. teishuki@mail.ncku.edu.tw.
authors.forename: Hsiu-Chi
authors.initials: HC
authors.lastname: Cheng
authors.affiliation: Departments of Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. weilun1@mail.ncku.edu.tw.|Department of Internal Medicine, National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan, 70428, Taiwan. weilun1@mail.ncku.edu.tw.
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Chang
authors.affiliation: Departments of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. cclu@mail.ncku.edu.tw.
authors.forename: Cheng-Chan
authors.initials: CC
authors.lastname: Lu
authors.affiliation: Departments of Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. sheubs@mail.ncku.edu.tw.|Department of Internal Medicine, National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan, 70428, Taiwan. sheubs@mail.ncku.edu.tw.
authors.forename: Bor-Shyang
authors.initials: BS
authors.lastname: Sheu
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications / Q000453:epidemiology* / Q000235:genetics / Q000382:microbiology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008679:Metaplasia / Q000453:epidemiology / Q000235:genetics; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics; D000071164:Trefoil Factor-2
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C000604007:TFF2 protein, human; D000071164:Trefoil Factor-2; C451060:spasmolytic polypeptide