3020insC NOD2/CARD15 polymorphism associated with treatment of colorectal cancer (original) (raw)
Related papers
Association between mutations in theCARD15/NOD2 gene and colorectal cancer in a Greek population
International Journal of Cancer, 2005
Epidemiological observations suggest that cancer arises from chronically inflamed tissues. Inflammatory bowel disease (IBD) is a typical example since patients with longstanding IBD are at increased risk for development of colorectal cancer (CRC). Therefore, genetic factors predisposing to or implicated in the chronic inflammatory process in IBD may simultaneously predispose to CRC. Recently CARD15/NOD2 has been associated with IBD, which further strengthens the notion that the inflammatory response plays a crucial role in this disease. Several mutations have been identified in the CARD15/NOD2 gene, which appear with significantly higher frequency in patients with IBD. In this report, we have examined the frequency of the 3 major mutations R702W, G908R and 3020insC of the CARD2/ NOD2 gene in a series of 104 consecutive Greek patients with sporadic colorectal cancer and 100 healthy individuals. The frequency of all the mutations was significantly elevated compared to the control population (R702W, OR,00.5؍ p;320.0؍ G908R, OR,87.2؍ p;520.0؍ 3020insC, OR,44.2؍ p.)710.0؍ Patients with advanced stage tumors were more frequently carriers of at least 1 variant in the CARD15/NOD2 gene (p.)900.0؍ Our results suggest that CARD2/NOD2 may be a genetic factor that predispose to sporadic colorectal cancer.
NOD2/CARD15 gene mutations in North Algerian patients with inflammatory bowel disease
World journal of gastroenterology : WJG, 2015
To analyse allelic frequency of NOD2 gene variants and to assess their correlation with inflammatory bowel disease (IBD) in Algeria. We studied 132 unrelated patients diagnosed with IBD, 86 with Crohn's disease (CD) and 46 with ulcerative colitis (UC). Data was prospectively collected between January 2011 and December 2013. The demographic and clinical characteristics were recorded for all the patients. A group of 114 healthy unrelated individuals were selected as controls. All groups studied originated from different regions of North Algeria and confirmed the Algerian origin of their parents and grandparents. Informed and written consent was obtained from each of the participants. All individuals were genotyped for the three CD-associated NOD2 variants (p.Arg(702)Trp, p.Gly908Arg and p.Leu(1007)fsinsC mutations) using the polymerase chain reaction-restriction fragment length polymorphism method. Allele and genotype frequencies in patients and control subjects were compared by χ...
The NOD2 3020insC Mutation and the Risk of Colorectal Cancer
Cancer Research, 2004
Several predispositions to colorectal cancer have been identified, but little is known about genetic susceptibilities to disease in older persons. Colorectal cancer is a risk in Crohn's disease and is believed to be associated with an inappropriate inflammatory response. Recently, the NOD2 gene has been associated with Crohn's disease, which further strengthens the notion that the inflammatory response plays a crucial role in this disease. Several mutations have been identified in the NOD2 gene, which appear with significantly higher frequency in patients with the disease. One such mutation (3020insC) is believed to be clearly causative because it results in a prematurely truncated protein with a predicted reduction in functional efficiency. In this report, we have examined the frequency of the 3020insC mutation in a series of 856 individuals including 556 patients with colorectal cancer. The frequency of the 3020insC mutation in a consecutive series of 250 non-hereditary nonpolyposis colorectal cancer patients >50 years of age was significantly elevated compared with the control population (odds ratio, 2.23; P ؍ 0.0046). The results indicate that NOD2 may be a predisposing factor to colorectal cancer characterized by an older average age of disease onset in persons who do not harbor any other genetic predisposition to disease.
BMC Cancer, 2007
Background: Epidemiological observations suggest that cancer arises from chronically inflamed tissues. Inflammatory bowel disease (IBD) is a typical example as patients with longstanding IBD are at an increased risk for developing colorectal cancer (CRC) and mutations of the NOD2/CARD15 gene increase the risk for Crohn's disease (CD). Recently, NOD2/CARD15 has been associated with a risk for CRC in some studies, which stemmed from ethnically diverse populations. Our aim was to identify common NOD2/CARD15 mutations in Hungarian patients with sporadic CRC. Methods: A total of 194 sporadic CRC patients (m/f: 108/86, age at diagnosis of CRC: 63.2 ± 9.1 years old) and 200 healthy subjects were included. DNA was screened for SNP8, SNP12 and SNP13 NOD2/CARD15 mutations by denaturing-HPLC and confirmed by direct sequencing. Results: NOD2/CARD15 mutations were found in 28 patients (14.4%) and in 23 controls (11.5%, p = NS). Allele frequencies for SNP8/R702W (1.8% vs. 1.5%) SNP12/G908R (1.8% vs. 1.8%) and SNP13/3020insC (3.6% vs. 2.5%) were also not statistically different between patients and controls. The clinicopathologic characteristics of CRC patients with or without NOD2/CARD15 mutations were not significantly different. Conclusion: Our results suggest that common NOD2/CARD15 mutations alone do not contribute to CRC risk in the Hungarian population.
European Journal of Gastroenterology & Hepatology, 2006
Background Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with variations in localization and behaviour. Mutations in the NOD2/CARD15 gene on chromosome 16q have been implicated in the pathogenesis of the disease and three main sequence variants, all single nucleotide polymorphisms (SNPs), have been identified in North American and European populations. Aims and methods As no data exist in the Croatian population, we consecutively collected a cohort of 136 CD patients and 91 healthy controls to determine the prevalence of NOD2/CARD15 mutations and their association with phenotypic expression of the disease. All patients and controls were genotyped for Arg702Trp (Hugot SNP8), Gly908Arg (Hugot SNP12), and Leu1007fsinsC (Hugot SNP13) and allele frequencies were compared between the Crohn's patients and controls. The correlation of NOD2/CARD15 genotypes with the phenotypic expression of Crohn's disease was further assessed by logistic regression analysis. Results NOD2/CARD15 variants were found in 38/136 CD patients (27.9%) compared to 10/91 (10.9%) healthy controls (P = 0.0022). Allele frequencies in patients with CD were 13.97%, 4.4% and 11.76%, respectively, for SNP8, 12 and 13, compared to 5.49%, 1.12% and 4.40% in controls (P = 0.041, P = 0.162, P = 0.055). Six CD patients carried double mutations and, remarkably, we identified two homozygous mutants amongst the healthy control group. Surgery over the course of the disease and a younger age at onset of the disease were significantly more frequent in patients who were carriers of NOD2/CARD15 mutations. Conclusions This report on NOD2/CARD15 mutations in Croatian patients with CD demonstrates that this gene is also implicated in susceptibility to CD in the Croatian population. Phenotypic association showed a younger age at diagnosis and a higher need for surgery in patients carrying NOD2/CARD15 mutations. However, the prevalence is somewhat lower compared to other reports, likely due to a more prominent colonic inflammation.
NOD2 3020insC Alone Is Not Sufficient for Colorectal Cancer Predisposition
Cancer Research, 2004
have been shown to associate with increased susceptibility to Crohn's disease. A recent Polish study linked the truncating NOD2 3020insC variant with an increased risk of colorectal cancer (CRC) at an older age (>50 years) of disease onset, with an odds ratio of 2.23. We studied the possible contribution of the 3020insC variant to CRC risk in a series of 1,042 Finnish population-based patients from which 926 samples were successfully analyzed and in 348 anonymous cancer-free controls. The frequency of the 3020insC mutation was 3.7% in both CRC patients (34 of 926, including 1 homozygote) and cancer-free controls (13 of 348; odds ratio, 0.98; confidence interval, 0.51-1.88). Contrary to the Polish study, there was no significant difference in the mutation rates between CRC patients > 50 years of age (25 of 576; 4.3%) and controls in the present series. We studied respective tumor tissue DNAs of all patients displaying heterozygous 3020insC changes for loss of heterozygosity. Loss of heterozygosity at NOD2 was observed in only 1 of the 33 CRC samples. Our results suggest that NOD2 3020insC alone does not contribute to CRC risk. If this variant predisposes to CRC, additional factors not present in the Finnish population need to be involved.
2009
NOD2/CARD15 gene variants may be associated with distinct phenotypic expressions of Crohn's disease, however, this association may change according to the ethnic and regional variation. The aim of this study was to analyze the impact of NOD2/CARD15 gene mutations on disease phenotype in Turkish Crohn's disease patients. Fourty-five Crohn's disease patients (32 males, 13 females) with a mean age of 38.7 ± 12.1 (range: 19-78) were enrolled into this prospective study. The three major polymorphisms (R702W, G908R, 3020insC) on NOD2/CARD15 gene were studied from the peripheral blood genomic DNA. R702W and G908R mutations were studied by PCR-RFLP method, and 3020insC mutation was studied by DNA sequencing. No homozygous mutation was detected. Heterozygous R702W, G908R, and 3020insC mutations were detected in 4, 3, and 4 patients, respectively. The frequency of R702W, G908R, and 3020insC mutations was found to be 4.4, 3.3, and 4.4%, respectively. The overall mutation frequency was found to be 12.2%. There was no statistically difference between the clinical course of the patients with (n = 11) and without (n = 34) mutations (p>0.05). NOD2/CARD15 gene polymorphisms do not have impact on disease phenotype in Turkish Crohn's disease patients.
Gastroenterology, 2002
Background & Aims: Mutations in the NOD2 gene are strongly associated with susceptibility to Crohn's disease (CD). We analyzed a large cohort of European patients with inflammatory bowel disease to determine which mutations confer susceptibility, the degree of risk conferred, their prevalence in familial and sporadic forms of the disease, and whether they are associated with site of disease. Methods: Individuals were genotyped for 4 NOD2 mutations: P268S, R702W, G908R, and 3020insC. Allelic transmission distortion to 531 CD-and 337 ulcerative colitis-affected offspring was assessed by the transmission disequilibrium test. Association was also tested in an independent cohort of 995 patients with inflammatory bowel disease and 290 controls. Cases were stratified by disease site and compared across NOD2 genotypes. Results: R702W, G908R, and 3020insC were strongly associated with CD but not with ulcerative colitis. Linkage disequilibrium was observed between P26BS and the other mutations, forming 3 independent disease' haplotypes. Genotype relative risks were 3.0 for mutation heterozygotes and 23.4 for homozygotes or compound heterozygotes. The frequency of NOD2 mutations was higher in cases from families affected only with CD and was significantly increased in ileal-specific disease cases compared with colon-specific disease (26.9% vs. 12.7%, P-0.0004). Conclusions: The R702W, G908R, and 3020insC mutations are strong independent risk factors for CD and are associated particularly with ileal disease.
Specific association of a CLEC16A/KIAA0350 polymorphism with NOD2/CARD15− Crohn's disease patients
European Journal of Human Genetics, 2009
Independent genome-wide association studies highlighted the function of CLEC16A/KIAA0350 polymorphisms modifying the risk to either multiple sclerosis (rs6498169) or type 1 diabetes (rs2903692). This C-type lectin gene maps to a linkage disequilibrium block at 16p13 and a functional role of this gene could be envisaged for other immune-related conditions, such as inflammatory bowel disease (IBD). The present study, aimed at investigating the association of those two polymorphisms with IBD, included 720 IBD patients and 550 ethnically matched healthy controls. The effect of rs2903692 previously described in diabetes was observed specifically for Crohn's disease (CD) patients lacking the main susceptibility factor described to date, that is, three polymorphisms within another pattern recognition gene, NOD2/CARD15 (NOD2 À vs NOD2 þ CD patients, G vs A: P ¼ 0.008; OR (95% CI) ¼ 1.54 (1.10-2.15); NOD2 À CD patients vs controls: P ¼ 0.008; OR (95% CI) ¼ 1.37 (1.08-1.73)). Replication of these findings was performed in independent Spanish cohorts of 544 IBD patients and 340 controls and the combined data yielded significant differences (405 NOD2 À vs 204 NOD2 þ CD patients, G vs A: P ¼ 0.0012; OR M-H (95% CI) ¼ 1.49 (1.17-1.90); NOD2 À CD patients vs controls: P ¼ 0.0007; OR M-H (95% CI) ¼ 1.35 (1.13-1.60)). The pooled analysis of the ulcerative colitis patients vs controls also yielded a significant risk (P ¼ 0.0005; OR (95% CI) ¼ 1.52 (1.19-1.93)). These data would suggest that microbial recognition through different pathways seems to converge in the development of these polygenic bowel diseases.
Detection of mutations in NOD2/Card15 gene in Arab patients with Crohn’s disease
2017
Background: Mutations in NOD2/CARD15 gene have been linked to an increased risk of Crohn's disease (CD). The objective of this study is to determine NOD2/CARD15 gene mutations, and their association with the risk of CD in Arabs in Kuwait. Methods: Four NOD2 gene mutations, including Pro268Ser (SNP5), Arg702Trp (SNP8), Gly908Arg (SNP12), and Leu1007FsinsC (SNP13) were examined in Arab CD patients (n = 103) and control subjects (n = 100). The genomic DNA was isolated and used in polymerase chain reaction (PCR) with four sets of specific primers. The PCR-amplified DNA fragments were sequenced and analyzed for the NOD2 mutations. Logistic regression was used to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (CI). Results: Of the four genotyped variants, the Arg702Trp (SNP8) and Leu1007FsinsC (SNP13) variants were not informative in our study sample due to minor allele frequency of <1%. The Pro268Ser (SNP5) mutation was detected in 17 (16.5%) CD patients and 32 (32.0%) controls. The Gly908Arg (SNP12) mutation was observed in 24 (23.3%) patients and 10 (10.0%) controls. In the dominant genetic risk model (i.e. carrying at least one minor allele), CD patients compared to controls were less likely to carry either the "CT" or "TT" genotype of variant Pro268Ser (SNP5; aOR = 0.43, 95% CI: 0.22-0.84). In contrast, CD patients compared to controls were more likely to carry the homozygous for the minor allele or the heterozygous genotypes of variant Gly908Arg (SNP12; aOR = 2.67, 95% CI: 1.19-5.97). Conclusions: In this Arab population, carrying at least one copy of the minor allele of Gly908Arg (SNP12) mutation in NOD2 gene was associated with increased susceptibility to CD, while having the heterozygous or homozygous for the minor allele genotype of the Pro268Ser (SNP5) mutation provided protection against CD. Mutations in Arg702Trp (SNP8) and Leu1007FsinsC (SNP13) were not detected in this sample of the Arab population in Kuwait.