MBL2 Gene Variants Research Articles

A Mannose-Binding Lectin-Defective Haplotype Is a Risk Factor for Gastric Cancer

El-Omar et al. (1) reported that interleukin (IL)-1 gene cluster variants that enhance the production of IL-1β (a powerful inhibitor of gastric acid secretion) increase the risk of gastric cancer in Helicobacter pylori (HP)-infected patients. IL-1β production is down-regulated by mannose-binding lectin (MBL) (2), an acute-phase glycoprotein that has a high affinity for gram-negative lipopolysaccharide and exerts immunological activity (3)(4). Variants in the promoter, the 5′UTR, and exon 1 of the MBL2 gene reduce the synthesis and activity of MBL (5). To assess the relationships between MBL2 gene variants and HP-related gastric cancer, we analyzed the whole coding region and the 5′UTR of the MBL2 gene in DNA extracted (QIAamp, Qiagen) from neoplastic cells embedded in paraffin sections (used for histological diagnosis) from 145 unrelated patients (90 males) affected by noncardia gastric cancer. Eighty-seven (60.0%) had intestinal-type; 47 (32.4%), diffuse-type; and 11 (7.6%), mixed-type adenocarcinoma. All patients had HP-positive serology. For 75 patients, we …

Mannose‐binding lectin‐2 genetic variation and stomach cancer risk

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. 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.