RESUMEN
Growth factors are polypeptides that are critical for the initiation, progression, and metastasis of cancer. Most tumor cells are capable of synthesizing particular growth factors leading to constitutive pathway activation in these cells through autocrine signaling. Epidermal growth factor (EGF) is a potent mitogenic peptide that exerts direct effects on the proliferation and differentiation of tumor cells in carcinogenesis. By contrast, vascular endothelial growth factor (VEGF) is vital for the invasion and metastasis of neoplasms through the formation of new blood vessels from mature endothelial cells. In this study, we investigated the association between functional polymorphisms of both the EGF and VEGF genes and colorectal cancer (CRC) susceptibility. A total of 130 CRC patients and 212 healthy controls were recruited for this case-control study. Genotyping of genetic variants was conducted via real-time polymerase chain reaction (PCR) amplification with allele-specific TaqMan probes. None of the genotypes of the EGF +61 A>G and VEGF +936 C>T variants was significantly associated with CRC susceptibility among the Malaysian subjects evaluated (P > 0.05). The observed frequency distributions of the EGF +61 A>G polymorphism genotypes showed ethnic heterogeneity, which was not the case for the VEGF +936 C>T genotypes. In conclusion, no positive correlation between these functional polymorphisms and CRC risk was found in this Malaysian population. Studies of the EGF and VEGF genes and CRC susceptibility are scarce, and the results reported thus far differ from one population to another. Hence, more replication studies are warranted before any firm conclusions can be made.
Asunto(s)
Neoplasias Colorrectales/genética , Factor de Crecimiento Epidérmico/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Factor A de Crecimiento Endotelial Vascular/genética , Alelos , Pueblo Asiatico , Estudios de Casos y Controles , Neoplasias Colorrectales/epidemiología , Frecuencia de los Genes , Genotipo , Humanos , Malasia/epidemiología , Oportunidad RelativaRESUMEN
Colorectal cancer (CRC) is one of the most common types of cancer in both developed and developing countries. This disease is triggered by and progresses via the sequential accumulation of multiple genetic alterations. In addition, the interaction between low-penetrance genes and environmental factors can also increase the risk of developing CRC. Since inflammatory bowel diseases (IBDs) are one of the predisposing factors for CRC, IBD-related genes might, to a certain extent, be associated with cancer initiation. The nucleotide oligomerization domain 2/caspase activating recruitment domain 15 gene (NOD2/CARD15) is the most well-established gene to be associated with increased susceptibility to Crohn's disease. Thus, various studies have been performed to investigate the potential contribution of this gene to CRC risk. In this study, we aimed to determine the frequency of the Arg702Trp, Gly908Arg, 3020insC, Pro268Ser, and JW1 variants of NOD2/CARD15, and to investigate their association with CRC susceptibility. A total of 130 CRC patients and 212 healthy controls were recruited for this study. Subsequently, real-time polymerase chain reaction with TaqMan was performed for the genotyping of these NOD2/ CARD15 variants. None of the NOD2/CARD15 variants was statistically associated to CRC susceptibility in our Malaysian population. Our findings were remarkably similar to those of other Asian cohorts, which indicated that these NOD2/CARD15 variants exhibit genetic heterogeneity between Caucasian and Asian populations.
Asunto(s)
Pueblo Asiatico/genética , Neoplasias Colorrectales/genética , Variación Genética , Proteína Adaptadora de Señalización NOD2/genética , Alelos , Estudios de Casos y Controles , Frecuencia de los Genes , Estudios de Asociación Genética , Heterogeneidad Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Malasia , Oportunidad Relativa , Polimorfismo de Nucleótido SimpleRESUMEN
This study aimed to investigate the potential association of TYK2 and STAT3 genes with the susceptibility to Crohn's disease (CD) among Malaysians. DNA samples were obtained from 80 CD patients and 100 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism methods were employed for genotyping, followed by statistical analysis. In our current study, none of the single nucleotide polymorphisms of either TYK2 or STAT3 was statistically associated with the susceptibility to CD in our local population (P > 0.05). In contrast, there was a statistically significant association between the G/G homozygotes of the STAT3 rs2293152 and the healthy control group (χ(2) = 6.229, P < 0.05). In conclusion, our study does not support the role of the TYK2 and STAT3 genes influencing CD susceptibility.
Asunto(s)
Pueblo Asiatico/genética , Enfermedad de Crohn/genética , Factor de Transcripción STAT3/genética , TYK2 Quinasa/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Heterocigoto , Homocigoto , Humanos , Malasia , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido SimpleRESUMEN
Crohn's disease is a chronic, relapsing inflammatory bowel disease; it affects the mucosa and deeper layers of the digestive wall. Two Crohn's disease patients who carried the JW1 variant and two patients who carried the SNP5 variant were investigated for other co-inherited polymorphisms that could influence Crohn's disease development. Based on the sequencing results, a homozygous 5'-UTR-59 G to A variant in exon 1 (SNP6) was observed in a patient who carried SNP5, while a heterozygous SNP6 variant was detected in the other patient who carried SNP5. No other associated mutations or polymorphisms were detected in the two patients who carried the JW1 variant of the CARD15/NOD2 gene.