title: CARD15 mutations and colorectal cancer in a South European country.
abstract: OBJECTIVE
  CARD15 mutations are associated with higher susceptibility to Crohn's disease (CD) and longstanding colonic CD increases the risk of developing colorectal cancer (CRC). The relation between these mutations and sporadic CRC remains controversial. The aim of this study was to assess whether germline and/or somatic CARD15 mutations are risk factors for sporadic CRC in Portugal and whether there are genotype-phenotype correlations in these patients.
  
  
  METHODS
  The three main CARD15 mutations (R702W, G908R and 3020insC) were researched in 112 sporadic CRC patients and 152 healthy subjects.
  
  
  RESULTS
  Overall, CARD15 mutations were found in 18 patients (16.1%) and in 15 controls (9.9%; p = 0.132). Individually, the incidence of R702W was significantly higher in patients than in controls (12.5% vs. 5.3%, p = 0.035), whereas the genotype frequencies for G908R (2.7% vs. 3.3%) and 3020insC (0.9% vs. 1.3%) were not statistically different between the two groups. Entire genotypic agreement was found in patients genotyped for blood and neoplastic DNA. A significantly higher incidence of CARD15 mutations was detected in patients with CRC diagnosed under 60 years old (28.6% vs. 10.4%, p = 0.015) and in female patients (24.4% vs. 10.4%, p = 0.048). No associations were found between CARD15 mutations and family history, symptoms or CRC pathologic characteristics.
  
  
  CONCLUSIONS
  The CARD15 R702W variant might be a predisposing factor to sporadic CRC in Portugal, particularly in patients under 60-years old and in female patients. This susceptibility appears to be linked with germline CARD15 mutations. Nevertheless, we have found no evidence that CARD15 mutations predict the pathologic characteristics of CRC.
authors.affiliation: Department of Gastroenterology, Coimbra University Hospital, Coimbra, Portugal. pauloavfreire@gmail.com
authors.forename: Paulo
authors.initials: P
authors.lastname: Freire
authors.forename: Francisco
authors.initials: F
authors.lastname: Portela
authors.forename: Maria M
authors.initials: MM
authors.lastname: Donato
authors.forename: Pedro
authors.initials: P
authors.lastname: Figueiredo
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferreira
authors.forename: Pedro
authors.initials: P
authors.lastname: Amaro
authors.forename: Anabela
authors.initials: A
authors.lastname: Sá
authors.forename: Paulo
authors.initials: P
authors.lastname: Andrade
authors.forename: Hermano
authors.initials: H
authors.lastname: Gouveia
authors.forename: Carlos
authors.initials: C
authors.lastname: Sofia
mesh_terms: D000367:Age Factors; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004273:DNA, Neoplasm; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D011174:Portugal / Q000453:epidemiology; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D004273:DNA, Neoplasm; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein