Mannose-binding lectin-2 genetic variation and stomach cancer risk
Corresponding Author
Andrea Baccarelli
EPOCA Epidemiology Research Centre, Maggiore Hospital IRCCS Foundation, University of Milan, Milan, Italy
Fax: +1-617-384-8745
Exposure, Epidemiology and Risk Program, Harvard School of Public Health, 401 Park Drive, Landmark Center, Suite 412F West, P.O. Box 15698, Boston, MA 02215, USASearch for more papers by this authorLifang Hou
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorJinbo Chen
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorJolanta Lissowska
Division of Cancer Epidemiology and Prevention, Cancer Centre and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland
Search for more papers by this authorEmad M. El-Omar
Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
Search for more papers by this authorPaolo Grillo
EPOCA Epidemiology Research Centre, Maggiore Hospital IRCCS Foundation, University of Milan, Milan, Italy
Search for more papers by this authorSara M. Giacomini
EPOCA Epidemiology Research Centre, Maggiore Hospital IRCCS Foundation, University of Milan, Milan, Italy
Search for more papers by this authorMeredith Yaeger
Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorToralf Bernig
Section on Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorWitold Zatonski
Division of Cancer Epidemiology and Prevention, Cancer Centre and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland
Search for more papers by this authorJoseph F. Fraumeni Jr
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorStephen J. Chanock
Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, National Institutes of Health, Bethesda, MD
Section on Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorWong-Ho Chow
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorCorresponding Author
Andrea Baccarelli
EPOCA Epidemiology Research Centre, Maggiore Hospital IRCCS Foundation, University of Milan, Milan, Italy
Fax: +1-617-384-8745
Exposure, Epidemiology and Risk Program, Harvard School of Public Health, 401 Park Drive, Landmark Center, Suite 412F West, P.O. Box 15698, Boston, MA 02215, USASearch for more papers by this authorLifang Hou
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorJinbo Chen
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorJolanta Lissowska
Division of Cancer Epidemiology and Prevention, Cancer Centre and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland
Search for more papers by this authorEmad M. El-Omar
Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
Search for more papers by this authorPaolo Grillo
EPOCA Epidemiology Research Centre, Maggiore Hospital IRCCS Foundation, University of Milan, Milan, Italy
Search for more papers by this authorSara M. Giacomini
EPOCA Epidemiology Research Centre, Maggiore Hospital IRCCS Foundation, University of Milan, Milan, Italy
Search for more papers by this authorMeredith Yaeger
Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorToralf Bernig
Section on Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorWitold Zatonski
Division of Cancer Epidemiology and Prevention, Cancer Centre and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland
Search for more papers by this authorJoseph F. Fraumeni Jr
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorStephen J. Chanock
Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, National Institutes of Health, Bethesda, MD
Section on Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorWong-Ho Chow
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorAbstract
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. © 2006 Wiley-Liss, Inc.
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