目的探讨中国汉族人群17q12-q21染色体上一个基因簇(ERBB2扩增子)的单核苷酸多态性(SNPs)是否与胃癌(GC)发病风险相关。我们在该基因簇中检测到26个SNP,该基因簇含有类固醇生成急性调节相关脂质转移结构域,含3(STARD3),蛋白磷酸酶1调节亚基1B(PPP1R1B/DARPP32),titin-cap(TCAP),含有1的per1样结构域(PERLD1/CAB2),人表皮生长因子受体2(ERBB2/HER2),锌指蛋白亚家族1A3(ZNFN1A3/IKZF3)和DNA拓扑异构酶2-α(TOP2A)基因在311例GC患者和425例Sequenom对照中。我们发现遗传变异与GC风险之间没有关联。然而,单倍型分析表明,STARD3的单倍型CCCT(rs9972882,rs881844,rs11869286和rs1877031)对GC易感性具有保护作用(P=0.043,比值比[OR]=0.805,95%置信区间[95%CI]=0.643-0.992)。STARD3rs1877031TC基因型证实了胃黏液腺癌和印戒细胞癌的组织发生(P=0.021,OR=2.882,95%CI=1.173-7.084)。我们使用免疫组织化学(IHC)分析和组织微阵列(TMA)检查了311例GC患者中243个肿瘤组织和20个邻近的正常胃组织中STARD3的表达。STARD3在胃壁细胞和胃肿瘤组织中的表达与性别显著相关(P=0.004)。饮酒(P<0.001),肿瘤位置(P=0.007),GC的组织学类型(P=0.005)和分化(P=0.023)。我们得出结论,STARD3单倍型CCCT的联合作用可能会影响GC敏感性。STARD3的表达可能与中国人群GC的发生有关。
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.