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Investigation of innate immunity genes CARD4, CARD8 and CARD15 as germline susceptibility factors for colorectal cancer.
BMC Gastroenterol ; 9: 79, 2009 Oct 20.
Article em En | MEDLINE | ID: mdl-19843337
ABSTRACT

BACKGROUND:

Variation in genes involved in the innate immune response may play a role in the predisposition to colorectal cancer (CRC). Several polymorphisms of the CARD15 gene (caspase activating recruitment domain, member 15) have been reported to be associated with an increased susceptibility to Crohn disease. Since the CARD15 gene product and other CARD proteins function in innate immunity, we investigated the impact of germline variation at the CARD4, CARD8 and CARD15 loci on the risk for sporadic CRC, using a large patient sample from Northern Germany.

METHODS:

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 (diagnosis) were performed for all CARD loci and subgroup analyses for diverse age strata were carried out for CARD15 mutations R702W, G908R and L1007fs. In addition, all SNPs were tested for association with disease presentation and family history of CRC.

RESULTS:

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 (diagnosis) with early disease manifestation the mutant allele of CARD15 R702W was found to be significantly associated with disease susceptibility (9.7% in cases vs 4.6% in controls; P(allelic) = 0.008, P(genotypic) = 0.0008, OR(allelic) = 2.22 (1.21-4.05) OR(ressessive) = 21.9 (1.96-245.4).

CONCLUSION:

Variation in the innate immunity genes CARD4, CARD8 and CARD15 is unlikely to play a major role in the susceptibility to CRC in the German population. But, we report a significant disease contribution of CARD15 for CRC patients with very early disease manifestation, mainly driven by variant R702W.
Assuntos

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 6_ODS3_enfermedades_notrasmisibles Base de dados: MEDLINE Assunto principal: DNA de Neoplasias / Neoplasias Colorretais / Proteínas Adaptadoras de Sinalização CARD / Proteína Adaptadora de Sinalização NOD1 / Proteína Adaptadora de Sinalização NOD2 / Imunidade Inata / Mutação / Proteínas de Neoplasias Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: BMC Gastroenterol Ano de publicação: 2009 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 6_ODS3_enfermedades_notrasmisibles Base de dados: MEDLINE Assunto principal: DNA de Neoplasias / Neoplasias Colorretais / Proteínas Adaptadoras de Sinalização CARD / Proteína Adaptadora de Sinalização NOD1 / Proteína Adaptadora de Sinalização NOD2 / Imunidade Inata / Mutação / Proteínas de Neoplasias Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: BMC Gastroenterol Ano de publicação: 2009 Tipo de documento: Article