Genetic variants in the IL1A gene region contribute to intestinal‐type gastric carcinoma susceptibility in European populations |
| |
| Authors: | Cecí lia Dur es,Xavier Mu oz,Catalina Bonet,Nadia Garcí a,Adoraci n Vencesl ,F tima Carneiro,B rbara Peleteiro,Nuno Lunet,Henrique Barros,Bj rn Lindkvist,Marie‐Christine Boutron‐Ruault,H. B Bueno‐de‐Mesquita,Cosmeri Rizzato,Antonia Trichopoulou,Elisabete Weiderpass,Allessio Naccarati,Ruth C. Travis,Anne Tj nneland,Aurelio Barricarte Gurrea,Mattias Johansson,Elio Riboli,C u Figueiredo,Carlos Alberto Gonz lez,Gabriel Capell ,Jos Carlos Machado,Nú ria Sala |
| |
| Affiliation: | 1. Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), , Porto, Portugal;2. Molecular Epidemiology Group, Translational Research Laboratory, Catalan Institute of Oncology (IDIBELL), , Barcelona, Spain;3. Hereditary Cancer Program, Translational Research Laboratory, Catalan Institute of Oncology (ICO‐IDIBELL), , Barcelona, Spain;4. Unit of Nutrition Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (IDIBELL), , Barcelona, Spain;5. Faculty of Medicine of the University of Porto, , Porto, Portugal;6. Department of Pathology, Hospital of S. Jo?o, , Porto, Portugal;7. Institute of Public Health of the University of Porto (ISPUP), , Porto, Portugal;8. Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, , Gothenburg, Sweden;9. Institut National de la Santé et de la Recherche Médicale (INSERM), Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, , Villejuif, France;10. Université Paris‐Sud, , Villejuif, France;11. Institut Gustave Roussy (IGR), , Villejuif, France;12. National Institute for Public Health and the Environment (RIVM), , Bilthoven, The Netherlands;13. Department of Gastroenterology and Hepatology, University Medical Centre, , Utrecht, The Netherlands;14. School of Public Health, Imperial College London, St Mary's Campus, Imperial College, , London, United Kingdom;15. German Cancer Research Center (DKFZ), , Heideflberg, Germany;16. Hellenic Health Foundation, , Athens, Greece;17. Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, , Athens, Greece;18. Department of Community Medicine, Faculty of Health Sciences, University of Troms?, , Troms?, Norway;19. Department of Research, Cancer Registry of Norway, , Oslo, Norway;20. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, , Stockholm, Sweden;21. Samfundet Folkh?lsan, , Helsinki, Finland;22. HuGeF (Human Genetics Foundation), Molecular and Genetic Epidemiology Unit, , Torino, Italy;23. Cancer Epidemiology Unit, University of Oxford, , Oxford, United Kingdom;24. Diet, Genes and Environment, Danish Cancer Society Research Center, , Copenhagen, Denmark;25. Navarre Public Health Institute, , Pamplona, Spain;26. Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública‐CIBERESP), , Madrid, Spain;27. International Agency for Research on Cancer (IARC‐WHO), , Lyon, France |
| |
| Abstract: | The most studied genetic susceptibility factors involved in gastric carcinoma (GC) risk are polymorphisms in the inflammation‐linked genes interleukin 1 (IL1) B and IL1RN. Despite the evidence pointing to the IL1 region, definite functional variants reproducible across populations of different genetic background have not been discovered so far. A high density linkage disequilibrium (LD) map of the IL1 gene cluster was established using HapMap to identify haplotype tagSNPs. Eighty‐seven SNPs were genotyped in a Portuguese case‐control study (358 cases, 1,485 controls) for the discovery analysis. A replication study, including a subset of those tagSNPs (43), was performed in an independent analysis (EPIC‐EurGast) containing individuals from 10 European countries (365 cases, 1284 controls). Single SNP and haplotype block associations were determined for GC overall and anatomopathological subtypes. The most robust association was observed for SNP rs17042407, 16Kb upstream of the IL1A gene. Although several other SNP associations were observed, only the inverse association of rs17042407 allele C with GC of the intestinal type was observed in both studies, retaining significance after multiple testing correction (p = 0.0042) in the combined analysis. The haplotype analysis of the IL1A LD block in the combined dataset revealed the association between a common haplotype carrying the rs17042407 variant and GC, particularly of the intestinal type (p = 3.1 × 10?5) and non cardia localisation (p = 4.6 × 10?3). These results confirm the association of IL1 gene variants with GC and reveal a novel SNP and haplotypes in the IL1A region associated with intestinal type GC in European populations. |
| |
| Keywords: | gastric carcinoma genetic susceptibility IL1 gene cluster IL1A haplotypes intestinal‐type gastric carcinoma |
|
|
