ALBERT

Description:    Colorectal cancer (CRC), one of the most frequent neoplasias worldwide, has both genetic and environmental causes. As yet, however, gene–environment (G × E) interactions in CRC have been studied mostly for a small number of candidate genes only. Therefore, we investigated the possible interaction, in CRC etiology, between single-nucleotide polymorphisms (SNPs) on the one hand, and overweight, smoking and alcohol consumption on the other, at a genome-wide level. To this end, we adopted a two-tiered approach comprising a case-only screening stage I (314 cases) and a case–control validation stage II (259 cases, 1,002 controls). Interactions with the smallest p value in stage I were verified in stage II using multiple logistic regression analysis adjusted for sex and age. In addition, we specifically studied known CRC-associated SNPs for possible G × E interactions. Upon adjustment for sex and age, and after allowing for multiple testing, however, only a single SNP (rs1944511) was found to be involved in a statistically significant interaction, namely with overweight (multiplicity-corrected p  = 0.042 in stage II). Several other G × E interactions were nominally significant but failed correction for multiple testing, including a previously reported interaction between rs9929218 and alcohol consumption that also emerged in our candidate SNP study (nominal p  = 0.008). Notably, none of the interactions identified in our genome-wide analysis was with a previously reported CRC-associated SNP. Our study therefore highlights the potential of an “agnostic” genome-wide approach to G × E analysis. Content Type Journal Article Category Original Investigation Pages 1-13 DOI 10.1007/s00439-012-1239-2 Authors Sabine Siegert, Section of Epidemiology, Institute of Experimental Medicine, Christian-Albrechts University Kiel, Kiel, Germany Jochen Hampe, Department of General Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany Clemens Schafmayer, Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Kiel, Germany Witigo von Schönfels, Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Kiel, Germany Jan-Hendrik Egberts, Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Kiel, Germany Asta Försti, Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany Bowang Chen, Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany Jesús Lascorz, Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany Kari Hemminki, Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany Andre Franke, Institute of Clinical Molecular Biology, Christian-Albrechts University Kiel, Kiel, Germany Michael Nothnagel, Institute of Medical Informatics and Statistics, Christian-Albrechts University Kiel, Brunswiker Straße 10, 24105 Kiel, Germany Ute Nöthlings, Section of Epidemiology, Institute of Experimental Medicine, Christian-Albrechts University Kiel, Kiel, Germany Michael Krawczak, Institute of Medical Informatics and Statistics, Christian-Albrechts University Kiel, Brunswiker Straße 10, 24105 Kiel, Germany Journal Human Genetics Online ISSN 1432-1203 Print ISSN 0340-6717