Background: Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against matrix proteins, particularly basement membrane constituents. A single nucleotide polymorphism (SNP) at ...-1306, which disrupts a Sp1-type promoter site (CCACC box), results in strikingly lower promoter activity with the T allele. In the present study, we investigated whether this MMP-2 genetic polymorphism might be associated with susceptibility to colorectal cancer (CRC) in the Saudi population. We also analyzed MMP-2 gene expression level sin CRC patients and 4 different cancer cell lines. Materials and Methods: TaqMan allele discrimination assays and DNA sequencing techniques were used to investigate the $C^{-1306}T$ SNP in the MMP-2 gene of Saudi colorectal cancer patients and controls. The MMP-2 gene expression level was also determined in 12 colon cancer tissue samples collected from unrelated patients and histologically normal tissues distant from tumor margins. Results and Conclusions: The MMP-2 $C^{-1306}T$ SNP in the promoter region was associated with CRC in our Saudi population and the MMP-2 gene expression level was found to be 10 times higher in CRC patients. The MMP-2 $C^{-1306}T$ SNP is significantly associated with CRC in the Saudi population and this finding suggested that MMP-2 variants might help predict CRC progression risk among Saudis. We propose that analysis of this gene polymorphism could assist in identification of patient subgroups at risk of a poor disease outcome.
Background: The Saudi population has experienced a sharp increase in colorectal and gastric cancer incidences within the last few years. The relationship between gene polymorphisms of xenobiotic ...metabolizing enzymes and colorectal cancer (CRC) incidence has not previously investigated among the Saudi population. The aim of the present study was to investigate contributions of CYP1A1, CYP2E1, and GSTM1 gene polymorphisms. Materials and Methods: Blood samples were collected from CRC patients and healthy controls and genotypes were determined by polymerase chain reaction restriction fragment length polymorphism and sequencing. Results and Conclusions: $CYP2E1^*6$ was not significantly associated with CRC development (odd ratio=1.29; confidence interval 0.68-2.45). A remarkable and statistically significant association was observed among patients with $CYP1Awt/^*2A$ (odd ratio=3.65; 95% confidence interval 1.39-9.57). The $GSTM1^*0/^*0$ genotype was found in 2% of CRC patients under investigation. The levels of CYP1A1, CYP2E1 and GSTM1 mRNA gene expression were found to be 4, 4.2 and 4.8 fold, respectively, by quantitative real time PCR. The results of the present case-control study show that the studied Saudi population resembles Caucasians with respect to the considered polymorphisms. Investigation of genetic risk factors and susceptibility gene polymorphisms in our Saudi population should be helpful for better understanding of CRC etiology.
Our aim was to evaluate the association between the expression and the polymorphism of TLR4/NF-KB pathways and colon cancer. TLR4 (rs4986790, rs10759932, rs10759931 and rs2770150) were genotyped in ...blood samples from Colorectal patients and healthy controls. TLR4 and cytokines inflammatory expression were evaluated by real time PCR on 40 matching normal and colon tissues and the protein level by Immunohistochemistry. The high level of TLR4 expression in colon cancer tissues is mainly due to infections by bacteria in the human colon and leads to induction of an acute secretion of inflammatory cytokines mediated by NF-KB. Also, we report here a clear evidence for an association between TLR4 rs10759931 polymorphism (OR = 0.086, CI: 0.04-0.18, P = <0.00001). This polymorphism affects the entire population without being specific to either gender or to any age group. In contrast, the rs2770150 is associated with colon cancer in women aged over 50 years and is closely linked with the decreased levels of female sex hormones during the post-menopausal period (OR = 0.188, CI: 0.074-0.48, P = <0.00084). rs10759932 and rs4986790 appear to have any association with colon cancer. Our data suggest that TLR4 SNPs could possibly serve as biomarkers for decision making in colon cancer treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
Inflammatory changes such as subepithelial edema and excessive inflammatory cell infiltration have been observed in uvular
tissues of obstructive sleep apnea (OSA) subjects. The levels of ...proinflammatory cytokines such as tumor necrosis factor (TNF)-α
and interleukin-6 are elevated in the serum of apneic patients and have been proposed as mediators of muscle weakness. TNF-α
has been shown to affect diaphragm contractility in mice and rabbit in vivo .
Objectives:
To assess total and compartmental TNF-α expression in uvular tissues of apneic and nonapneic patients.
Methods:
Uvular tissues were collected from 14 snorers without sleep disorders breathing, 14 subjects with OSA (OSA 1 group) whose
body mass index (BMI) was similar to that of snorers, and 12 additional obese OSA subjects (OSA 2 group) who underwent an
uvulopalatopharyngoplasty. Sections were examined using immunohistochemistry and Western blot analysis. TNF-α expression was
evaluated in the musculus uvulae (MU), epithelial layer, and perimuscular tissues from proximal uvular sections.
Results:
TNF-α was more highly expressed in whole uvular protein extracts of apneic groups than in snorers (mean ± SEM snorers, 100.5
± 3.0%; OSA 1 group, 127.1 ± 6.9%; OSA 2 group, 140.7 ± 11.0%; p = 0.01). In the muscular area, TNF-α levels were higher in
the more obese OSA subjects than in the other two groups (snorers, 100.3 ± 3%; OSA 1 group, 107.4 ± 0.7%; OSA 2 group, 124.1
± 4.2%; p = 0.007). In the muscular area, TNF-α was correlated with BMI, but no relationship was found with the apnea-hypopnea
index.
Conclusions:
We conclude that MU is the major TNF-α source in uvular tissue and that TNF-α is more highly expressed in the heaviest OSA
patients compared to less obese OSA patients and nonapneic snorers.
inflammation
musculus uvulae
obesity
sleep apnea
upper airways
Cytochrome P450 (CYP)19A1 encodes aromatase, the enzyme responsible for the conversion of androgens to estrogens, and may play a role in variation in outcomes among women with breast cancer. The aim ...of this study was to analyze the genetic association of rs4646 (A > C) and rs700518 (Val > Val) in the CYP19A1 gene with the risk of breast cancer.
These two single nucleotide polymorphisms (SNPs) were analyzed in a primary study group of breast cancer patients and healthy control subjects. Genotypes were determined by the TaqMan SNP analysis technique. The study data were analyzed using the chi-square or t-test and logistic regression analysis by Statistical Package for the Social Sciences version 16 software.
rs4646 and rs700518 had no association with susceptibility to breast cancer. There was no significant association for either of these SNPs overall in breast cancer samples when compared with healthy control samples. Our data do not support a relationship between the CYP19A1 rs4646 and rs700518 SNPs and risk of breast cancer. It may be that there are ethnic differences with regard to this relationship.
This study demonstrated that CYP19A1 rs4646 and rs700518 SNPs may not be involved in the etiology of breast cancer in the Saudi population. Confirmation of our findings in larger populations of other ethnicities could provide evidence for the role of the CYP19A1 gene in breast carcinomas.
Toll-like receptors (TLRs) play an important role in immune-surveillance and responses towards pathogenic and non-pathogenic microorganisms. They act as innate immune sensors against endogenous and ...exogenous danger signals by recognizing the pattern recognition molecules (DAMPs and PAMPs) and drive an adaptive immune response through their signaling pathways, which leads to NF-κB and IRF3 transactivation and induces different inflammatory cytokine genes. TLRs polymorphisms were investigated in various cancer types studies. However, precious studies have reported that the Polymorphisms on TLR1-TLR10 cluster have been associated with increased risk of prostate cancer. However, it has known that TLRs genetic variation is associated with increased the susceptibility to gastric cancer. A same synthetically meta- analysis also confirmed the association of TLRs with increased the gastrointestinal cancer but with decreased prostate cancer risk. Our previous studies have demonstrated a strong link between TLRs polymorphisms and colon cancer and breast cancer in Saudi Arabia population. Similar studies were analyzed with Korean patients with papillary thyroid cancer and their clinic-pathologic features in age matched controls by using direct sequencing. The general objective of this chapter was to investigate the role of different TLRs (i.e., TLR2, TLR4, and TLR6) polymorphisms and their association with cancer development.
The development of cancer involves genetic predisposition and a variety of environmental exposures. Genome-wide linkage analyses provide evidence for the significant linkage of many diseases to ...susceptibility loci on chromosome 8p23, the location of the human defensin gene cluster. Human beta -defensins (hBDs) are important molecules of innate immunity. This study was designed to analyze the expression and genetic variations in hBDs (hBD-1, hBD-2, hBD-3 and hBD-4) and their putative association with colon cancer. hBD gene expression and relative protein expression were evaluated by Real-Time polymerase chain reaction (qPCR) and immunohistochemistry, respectively, from 40 normal patients and 40 age-matched patients with colon cancer in Saudi Arabia. In addition, hBD polymorphisms were genotyped by exon sequencing and by promoter methylation. hBD-1, hBD-2, hBD-3 and hBD-4 basal messenger RNA expression was significantly lower in tumor tissues compared with normal tissues. Several insertion mutations were detected in different exons of the analyzed hBDs. However, no methylation in any hBDs promoters was detected because of the limited number of CpG islands in these regions. We demonstrated for the first time a link between hBD expression and colon cancer. This suggests that there is a significant link between innate immunity deregulation through disruption of cationic peptides (hBDs) and the potential development of colon cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
. DNA repair systems are essential for each cell to repair and maintain the genome integrity. Base excision repair pathway is one of the crucial pathways to maintain genome integrity and
plays a key ...role in BER pathway. The purpose of this study is to evaluate the association between polymorphisms in
3'untranslated region (3'UTR) SNP rs8679 and its expression in colorectal cancer.
. Genotyping and gene expression were performed using TaqMan assays. The effects of age, gender, and tumor location were evaluated in cases and controls regarding the genotyping results. Resulting data was analyzed using SPSS software.
. Genotyping analysis for SNP rs8679 showed decreased susceptibility to colorectal cancer at heterozygous TC allele and at minor allele C. Further this protective association was also observed in younger age patients (≤57), in female patients, and also in patients with tumors located at colon and rectum.
expression levels are significantly different in colorectal cancer compared to matched normal tissue. Our findings proved that the upregulation of
is associated with tumor progression and poor prognosis in Saudi patients with colorectal cancer, suggesting that
can be novel and valuable signatures for predicting the clinical outcome of patients with colorectal cancer.
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