title: Association analysis of ERBB2 amplicon genetic polymorphisms and STARD3 expression with risk of gastric cancer in the Chinese population.
abstract: The purpose of this study was to investigate whether risk of gastric cancer (GC) was associated with single nucleotide polymorphisms (SNPs) in a gene cluster on the chromosome 17q12-q21 (ERBB2 amplicon) in the Chinese Han population. We detected twenty-six SNPs in this gene cluster containing steroidogenic acute regulatory-related lipid transfer domain containing 3 (STARD3), protein phosphatase 1 regulatory subunit 1B (PPP1R1B/DARPP32), titin-cap (TCAP), per1-like domain containing 1(PERLD1/CAB2), human epidermal growth factor receptor-2 (ERBB2/HER2), zinc-finger protein subfamily 1A 3 (ZNFN1A3/IKZF3) and DNA topoisomerase 2-alpha (TOP2A) genes in 311 patients with GC and in 425 controls by Sequenom. We found no associations between genetic variations and GC risk. However, haplotype analysis implied that the haplotype CCCT of STARD3 (rs9972882, rs881844, rs11869286 and rs1877031) conferred a protective effect on the susceptibility to GC (P=0.043, odds ratio [OR]=0.805, 95% confidence intervals [95% CI]=0.643-0.992). The STARD3 rs1877031 TC genotype endued histogenesis of gastric mucinous adenocarcinoma and signet-ring cell carcinoma (P=0.021, OR=2.882, 95% CI=1.173-7.084). We examined the expression of STARD3 in 243 tumor tissues out of the 311 GC patients and 20 adjacent normal gastric tissues using immumohistochemical (IHC) analysis and tissue microarrays (TMA). The expression of STARD3 was observed in the gastric parietal cells and in gastric tumor tissues and significantly correlated with gender (P=0.004), alcohol drinking (P<0.001), tumor location (P=0.007), histological type (P=0.005) and differentiation (P=0.023) in GC. We concluded that the combined effect of haplotype CCCT of STARD3 might affect GC susceptibility. STARD3 expression might be related to the tumorigenesis of GC in the Chinese population.
authors.affiliation: Department of Biology, School of Life Sciences, Anhui Medical University, Hefei 230032, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Pathology, Anhui Medical University, Hefei 230032, China.
authors.forename: Zuo-Yang
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Department of Biology, School of Life Sciences, Anhui Medical University, Hefei 230032, China; State Key Laboratory & Incubation Base of Dermatology of Ministry of National Science and Technology, Anhui Medical University, Hefei 230032, China; Sektion Experimentelle Anaesthesiologie, Universitaetsklinikum Ulm, Ulm 89081, Germany. Electronic address: weidongdu@hotmail.com.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Du
authors.affiliation: Department of Biology, School of Life Sciences, Anhui Medical University, Hefei 230032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Biology, School of Life Sciences, Anhui Medical University, Hefei 230032, China.
authors.forename: Song
authors.initials: S
authors.lastname: Xu
authors.affiliation: State Key Laboratory & Incubation Base of Dermatology of Ministry of National Science and Technology, Anhui Medical University, Hefei 230032, China.
authors.forename: Xian-Bo
authors.initials: XB
authors.lastname: Zuo
authors.affiliation: State Key Laboratory & Incubation Base of Dermatology of Ministry of National Science and Technology, Anhui Medical University, Hefei 230032, China.
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Zhou
authors.affiliation: State Key Laboratory & Incubation Base of Dermatology of Ministry of National Science and Technology, Anhui Medical University, Hefei 230032, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: MVZ, ACURA Kliniken, Baden-Baden 76530, Germany.
authors.forename: Xue-Ling
authors.initials: XL
authors.lastname: Ma
authors.affiliation: Sektion Experimentelle Anaesthesiologie, Universitaetsklinikum Ulm, Ulm 89081, Germany.
authors.forename: Marion E
authors.initials: ME
authors.lastname: Schneider
authors.affiliation: Department of Biology, School of Life Sciences, Anhui Medical University, Hefei 230032, China.
authors.forename: Hong-Zhen
authors.initials: HZ
authors.lastname: Xia
authors.affiliation: Department of Biology, School of Life Sciences, Anhui Medical University, Hefei 230032, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Anhui Medical University, Hefei 230032, China.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Wu
authors.affiliation: Clinical Laboratory, the First Affiliated Hospital, Anhui Medical University, Hefei 230032, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yuan-Hong
authors.affiliation: State Key Laboratory & Incubation Base of Dermatology of Ministry of National Science and Technology, Anhui Medical University, Hefei 230032, China.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002681:China; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012306:Risk; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C105684:STARD3 protein, human
keywords: CI; EDTA; ERBB2; ERBB2 amplicon; GC; GRB7; Gastric cancer; HWE; HapMap; Hardy–Weinberg equilibrium; IHC; International HapMap Project; LD; MAF; MIEN1; OR; PBS; PCR; PERLD1; PNMT; PPP1R1B; SNP; STARD3; START; Single nucleotide polymorphism; TBE; TCAP; TMA; TOP2A; Tris/borate/EDTA; UTR; ZNFN1A3; confidence interval; epidermal growth factor receptor-2; ethylenediaminetetraacetic acid; gastric cancer; growth factor receptor-bound protein 7; immunohistochemistry; linkage disequilibrium; migration and invasion enhancer 1; minor allele frequency; odds ratio; per1-like domain-containing protein 1; phenylethanolamine N-methyltransferase; phosphate buffer saline; polymerase chain reaction; protein phosphatase 1 regulatory subunit 1B; single nucleotide polymorphism; steroidogenic acute regulatory-related lipid transfer; steroidogenic acute regulatory-related lipid transfer domain-containing 3; tissue microarray; titin-cap; topoisomerase (DNA) II alpha; untranslated regions; zinc-finger protein subfamily 1A3