CARD15 mutations and colorectal cancer in a South European country

Abstract

Purpose 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.

Role of NOD1/CARD4 and NOD2/CARD15 gene polymorphisms in cancer etiology

“…For Hungary, the main factor may be the insufficiency of sample size in the investigation of Lakatos et al [69]; for Poland, the major factor is obscure; and other possible reasons for these disparities may be similar to those that were suggested above for the rs2066847 polymorphism. As in the case with rs2066847, the similar age-dependent influence of the rs2066844 polymorphism on the CRC risk (higher in patients older than 50 -60 years) was detected in German [72] and Portuguese [75] populations.…”

“…For rs2066845 and rs2066844, results are also conflicting in different populations. Positive results were obtained in a Greek population [64] for rs2066845 polymorphism and in Greek [64], New Zealand [66], German [72] and Portuguese [75] populations for rs2066844 polymorphism. Nevertheless, in Finnish [63,68], Hungarian [69], and Polish [70,71] populations results for both of them were negative.…”

“…The positive correlation was also observed in the Greek population [64] despite the small sample size. However, studies in other populations (Finnish [63], New Zealand [66], Latvian [67], Hungarian [69], German [72], and Portuguese [75]) found no connection between rs2066847 polymorphism and CRC risk. These disparities in results among different ethnicities are, at first glance, unexpected.…”

“…Results obtained by Yazdanyar et al [74] in the Danish population showed that variant homozygotes may be characterized by strongly increased CRC risk, although results for each polymorphism separately are obscure. The last investigation de- voted to this problem was conducted by Freire et al [75] in the Portuguese population and higher CRC risk was revealed only for T allele of rs2066844.…”

Association between C13ORF31, NOD2, RIPK2 and TLR10 polymorphisms and urothelial bladder cancer

“…The NOD2 polymorphism GG (rs rs9302752) was associated with a higher frequency of lymph node metastases. NOD2 polymorphisms were previously associated with colorectal cancer risk [29], although Wex et al [30] did not find NOD2 genetic variants to be a risk factor for gastric carcinogenesis in a Caucasian population. In the present study, no association was found between NOD2 or TLR10 polymorphisms and bladder cancer risk.…”