Mannose-binding lectin-2 genetic variation and stomach cancer risk
Mannose-binding lectin-2 genetic variation and stomach cancer risk
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DOI：
10.1002/ijc.22075
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发表时间：
2006-10-15
影响因子：
6.4
通讯作者：
Chow, Wong-Ho
中科院分区：
文献类型：
--
作者：
Baccarelli, Andrea;Hou, Lifang;Chow, Wong-Ho
甘露糖结合凝集素 (MBL) 蛋白是一种参与全身和粘膜先天免疫的抗原识别分子，其缺乏是由 MBL2 基因启动子和外显子 1 区域中的变异等位基因决定的。我们对波兰华沙的 305 例胃癌病例和 427 例对照进行了一项基于人群的研究，以确定 MBL2 基因变异是否易患胃癌。 MBL2中的单核苷酸多态性(SNP)通过TaqMan(TM)测定。 5 个测试的 MBL2 变体处于完全连锁不平衡状态，包含 6 种不同的单倍型。调整年龄、性别、教育程度和吸烟情况后，相对于 L/L 携带者，携带 H/H 启动子基因型的受试者患胃癌的风险增加（OR = 1.8，95%CI 1.1-2.9；p = 0.020）。携带至少一个 D exon-1 等位基因与非显着的过度风险相关（OR = 1.5，95% CI 0.9-2.4；p = 0.081）。在单倍型分析中，与最常见的单倍型 HYA 相比，HYD 单倍型与胃癌风险增加相关（OR = 1.9，95% CI 1.1-3.2；p = 0.021）。在双倍型分析中，与 YA/YA 相比，携带 YA/D 单倍型组合的受试者显示出最高风险（OR = 3.0，95% CI 1.2-7.1；p = 0.015）。进一步分析检查 MBL2 和 IL-1B 多态性的联合效应（之前已证明易患胃癌），表明高危 IL-1B 基因型（位置 -511 处的 CT 或 TT）和 HYD MBL2 单倍型的组合与 3.5 倍的风险相关（OR = 3.5，95% CI 1.6-7.6；p = 0.001）。我们的研究结果表明，导致半胱氨酸 > 精氨酸替代的密码子 52 D MBL2 变体，而不是产生甘氨酸替代的 B 和 C 变体，与胃癌风险特别相关。 (c) 2006 年 Wiley-Liss, Inc.
Deficiency of the mannose-binding lectin (MBL) protein, an antigen-recognition molecule involved in systemic and mucosal innate immunity, is determined by variant alleles in MBL2 gene promoter and exon-1 regions. We conducted a population-based study on 305 stomach cancer cases and 427 controls in Warsaw, Poland to determine whether MBL2 gene variants predispose to stomach cancer. Single nucleotide polymorphisms (SNPs) in MBL2 were determined by TaqMan (TM). The 5 tested MBL2 variants are in complete linkage disequilibrium and comprise 6 different haplotypes. The risk of stomach cancer was increased in subjects carrying the H/H promoter genotype (OR = 1.8, 95%CI 1.1-2.9; p = 0.020) relative to L/L carriers, after adjustment for age, gender, education and smoking. Carrying at least one D exon-1 allele was associated with nonsignificant excess risk (OR = 1.5, 95% CI 0.9-2.4; p = 0.081). In haplotype analysis, the HYD haplotype was associated with increased risk of stomach cancer when compared with HYA, the most common haplotype (OR = 1.9, 95 % CI 1.1-3.2; p = 0.021). In diplotype analysis, subjects carrying the YA/D haplotype combination showed the highest risk (OR = 3.0, 95% CI 1.2-7.1; p = 0.015), compared with YA/YA. Further analyses to examine the joint effect of MBL2 and IL-1B polymorphisms, previously shown to predispose to stomach cancer, indicated that the combination of at-risk IL-1B genotypes (CT or TT at location -511) and HYD MBL2 haplotype was associated with a 3.5-fold risk (OR = 3.5, 95% CI 1.6-7.6; p = 0.001). Our findings suggest that the codon 52 D MBL2 variant causing a cysteine > arginine replacement, but not B and C variants producing glycine substitutions, is specifically associated with gastric cancer risk. (c) 2006 Wiley-Liss, Inc.