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Several polymorphisms of the<jats:italic>CARD15<\/jats:italic>gene (caspase activating recruitment domain, member 15) have been reported to be associated with an increased susceptibility to Crohn disease. Since the<jats:italic>CARD15<\/jats:italic>gene product and other CARD proteins function in innate immunity, we investigated the impact of germline variation at the<jats:italic>CARD4<\/jats:italic>,<jats:italic>CARD8<\/jats:italic>and<jats:italic>CARD15<\/jats:italic>loci on the risk for sporadic CRC, using a large patient sample from Northern Germany.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 1044 patients who had been operated with sporadic colorectal carcinoma (median age at diagnosis: 59 years) were recruited and compared to 724 sex-matched, population-based control individuals (median age: 68 years). Genetic investigation was carried out following both a coding SNP and haplotype tagging approach. Subgroup analyses for N = 143 patients with early manifestation of CRC (\u226450 age at diagnosis) were performed for all<jats:italic>CARD<\/jats:italic>loci and subgroup analyses for diverse age strata were carried out for<jats:italic>CARD15<\/jats:italic>mutations R702W, G908R and L1007fs. In addition, all SNPs were tested for association with disease presentation and family history of CRC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No significant differences were observed between the patient and control allelic or haplotypic spectra of the three genes under study for the total cohort (N = 1044 patients). None of the analysed SNPs was significantly associated with either tumour location or yielded significant association in the familial or non-familial CRC patient subgroups. However, in a patient subgroup (\u226445 age at diagnosis) with early disease manifestation the mutant allele of<jats:italic>CARD15<\/jats:italic>R702W was found to be significantly associated with disease susceptibility (9.7% in cases<jats:italic>vs<\/jats:italic>4.6% in controls; P<jats:sub>allelic<\/jats:sub>= 0.008, P<jats:sub>genotypic<\/jats:sub>= 0.0008, OR<jats:sub>allelic<\/jats:sub>= 2.22 (1.21-4.05) OR<jats:sub>ressessive<\/jats:sub>= 21.9 (1.96-245.4).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Variation in the innate immunity genes<jats:italic>CARD4<\/jats:italic>,<jats:italic>CARD8<\/jats:italic>and<jats:italic>CARD15<\/jats:italic>is unlikely to play a major role in the susceptibility to CRC in the German population. But, we report a significant disease contribution of<jats:italic>CARD15<\/jats:italic>for CRC patients with very early disease manifestation, mainly driven by variant R702W.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-230x-9-79","type":"journal-article","created":{"date-parts":[[2009,10,21]],"date-time":"2009-10-21T06:15:31Z","timestamp":1256105731000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Investigation of innate immunity genes CARD4, CARD8 and CARD15 as germline susceptibility factors for colorectal cancer"],"prefix":"10.1186","volume":"9","author":[{"given":"Nikolaus","family":"M\u00f6ckelmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Witigo","family":"von Sch\u00f6nfels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Buch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"von Kampen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bence","family":"Sipos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Hendrik","family":"Egberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Rosenstiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Franke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Brosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Hinz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"R\u00f6der","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Kalthoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich R","family":"F\u00f6lsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Krawczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schreiber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens Dieter","family":"Br\u00f6ring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Tepel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Schafmayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Hampe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,10,20]]},"reference":[{"issue":"7","key":"371_CR1","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1158\/1055-9965.1253.13.7","volume":"13","author":"K Hemminki","year":"2004","unstructured":"Hemminki K, Chen B: Familial risk for colorectal cancers are mainly due to heritable causes. 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