Predictors of Anti-TNF Therapy Failure among Inflammatory Bowel Disease (IBD) Patients in Saudi Arabia: A Single-Center Study.

BACKGROUND: The advent of monoclonal antibodies (mAbs) has revolutionized the management of many immune-mediated diseases such as inflammatory bowel disease (IBD). Infliximab and adalimumab were the first mAbs approved for the management of IBD, and are still commonly prescribed for the treatment of both Crohn's disease (CD) and ulcerative colitis (UC). Although mAbs have demonstrated high effectiveness rates in the management of IBD, some patients fail to respond adequately to mAbs, resulting in disease progression and the flare-up of symptoms. OBJECTIVE: The objective was to explore the predictors of treatment failure among IBD patients on infliximab (INF) and adalimumab (ADA)-as demonstrated via colonoscopy with a simple endoscopic score (SES-CD) of ≥1 for CD and a Mayo score of ≥2 for UC-and compare the rates of treatment failure among patients on those two mAbs. METHODS: This was a prospective cohort study among IBD patients aged 18 years and above who had not had any exposure to mAbs before. Those patients were followed after the initiation of biologic treatment with either INF or ADA until they were switched to another treatment due to failure of these mAbs in preventing the disease progression. Univariate and multiple logistic regressions were conducted to examine the predictors and rates of treatment failure. RESULTS: A total of 146 IBD patients (118 patients on INF and 28 on ADA) met the inclusion criteria and were included in the analysis. The mean age of the patients was 31 years, and most of them were males (59%) with CD (75%). About 27% and 26% of the patients had penetrating and non-stricturing-non-penetrating CD behavior, respectively. Patients with UC had significantly higher odds of treatment failure compared to their counterparts with CD (OR = 2.58, 95% CI [1.06-6.26], p = 0.035). Those with left-sided disease had significantly higher odds of treatment failure (OR = 4.28, 95% CI [1.42-12.81], p = 0.0094). Patients on ADA had higher odds of treatment failure in comparison to those on INF (OR = 26.91, 95% CI [7.75-93.39], p = 0.0001). CONCLUSION: Infliximab was shown to be more effective in the management of IBD, with lower incidence rates of treatment failure in comparison to adalimumab.

Association of HER1 and HER2 Gene Variants in the Predisposition of Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is a major health concern worldwide. A series of sequential accumulation of genetic and epigenetic changes are responsible for the initiation and progression of diseases via the normal > adenoma > carcinoma sequence. Genetic variants in crucial cancer-causing genes are known to mediate the risk of cancer. OBJECTIVE: In this case-control study, we examined single nucleotide polymorphism (SNP) in HER1 (rs763317 and rs3752651) and HER2 (rs1136201 and rs1058808) genes to assess their role in the susceptibility of CRC in a Saudi population. METHODS: TaqMan allelic discrimination assay was utilized to identify the genotypes in 163 normal and 143 CRC patients. RESULTS: In the overall analysis, the rs3752651 and rs1136201 were significantly associated with the risk of CRC. Although none of the examined SNPs had any impact on the age at which CRC was diagnosed, interestingly, three SNPs showed a significant association based on gender. The rs3752651 conferred significant protection only in men, whereas rs1136201 diminished the risk and rs1058808 considerably increased the susceptibility of CRC only in women. CONCLUSIONS: Our result suggests that these SNPs in HER1 and HER2 after validation in larger cohorts of different ethnicities may be utilized as genetic screening markers for predicting colorectal cancer predisposition.

Expression and Polymorphism of TSLP/TSLP Receptors as Potential Diagnostic Markers of Colorectal Cancer Progression.

Colorectal cancer (CRC) is the third most common malignancy and the fourth leading cause of cancer-related mortality worldwide. Inflammation is considered as a critical driver for CRC development and growth. We investigated the association between polymorphisms/expression levels of thymic stromal lymphopoietin (TSLP) /TSLP receptors and CRC risk in Saudi population. DNA samples were isolated from blood samples from 220 participants. Case subjects were 112 patients diagnosed with CRC, while control subjects were 108 healthy individuals, who were not diagnosed with any type of malignancy. We selected two single nucleotide polymorphisms (SNPs) located in the thymic stromal lymphopoietin gene (rs10043985 and rs2289276), three SNPs in TSLP receptor gene (TSLPR; rs36139698, rs36177645, and rs36133495), and two other SNPs in interleukin-7 receptor gene (IL-7R; rs12516866 and rs1053496), and designated these SNPs for a case-control genotyping study. The gene expression was analyzed using quantitative RT-PCR and immunohistochemistry assays array on 20 matching colorectal cancer/normal tissues. mRNA expressions and protein levels of TSLP, TSLPR-α subunit, and IL-7R-α subunit showed a 4-fold increase in colon cancer tissues when compared to normal colon tissues. Furthermore, two SNPs (rs10043985 of TSLP and rs1053496 of IL-7R) showed statistically significant correlations with CRC susceptibility. Interestingly, only rs10043985 showed a statistically significant association (p < 0.0001) in the genotypic and phenotypic levels with CRC for all clinical parameters (age, gender, and tumor location) tested. However, IL-7R rs1053496 genotyping results presented a significant correlation (p < 0.05) in male CRC patients and in individuals under 57 years of age. TSLP rs2289276, IL-7R rs12516866, and all TSLPR variants did not display any significant genotypic or phenotypic correlations in all tested clinical parameters. This study identified that TSLP rs10043985 and IL-7R rs1053496 SNPs, and the expression levels of TSLP and TSLPR-α subunit, can be used as markers for CRC development and treatment. However, additional investigations are required on larger group of patients from diverse ethnicities to confirm the genetic association of these variants to CRC.

NOTCH Single Nucleotide Polymorphisms in the Predisposition of Breast and Colorectal Cancers in Saudi Patients.

Breast cancer (BC) is a heterogeneous disease and is one of the most common malignancy affecting women worldwide while colorectal cancer (CRC) is estimated to be the third common cancer and second leading cause of cancer related death globally. Both BC and CRC involve multiple genetic and epigenetic alterations in genes belonging to various signaling pathways including NOTCH that has been implicated in the development of these cancers. We investigated four single nucleotide polymorphisms, each in genes encoding NOTCH1-4 receptors for their role in susceptibility to breast and colorectal cancers in Saudi population. In this case-control study, TaqMan genotypic analysis of rs3124591 in NOTCH1 and rs3820041 in NOTCH4 did not exhibit association with breast as well as colorectal cancers. However, a strong association of rs11249433 which is in close proximity to NOTCH2 was observed with breast cancer susceptibility especially with those having an early onset of the disease. Interestingly, the rs1043994 located in NOTCH3 showed gender preference and was found to be significantly associated with colorectal cancers in males. Validation of these findings in bigger populations of different ethnicities may prove beneficial in identifying rs11249433 and rs1043994 as genetic screening markers for early detection of breast and colorectal carcinomas, respectively.

Clinical characteristics, natural history, and outcomes of Crohn's-related intra-abdominal collections.

BACKGROUND: Intra-abdominal collections in the form of abscesses or matted bowel loops, called phlegmons, might occur in patients with Crohn's disease (CD). The clinical characteristics and management of such conditions are not well described. We aim to characterize CD-related intra-abdominal collections clinically, and identify predictors of need for surgical interventions and the time to surgery. METHODS: We utilized the Saudi Inflammatory Bowel Disease Information System (IBDIS) database to identify all patients treated for radiologically proven intra-abdominal abscesses or phlegmons since inception. Demographics, clinical data, clinical course, and treatment outcomes were recorded. Logistic regression analysis and survival analysis were used to identify predictors of surgical resection and differences in time to surgery between patient subgroups, respectively. RESULTS: A total of 734 patients with a diagnosis of CD were screened and 75 patients were identified. The mean age was 25.6 ± 9.9 years and 51% were males. Nearly 60% of patients had abscesses larger than 3 cm while 13% had smaller abscesses and 36% had phlegmons. On presentation, the most commonly reported symptom was abdominal pain (99%) followed by weight loss (27%). About 89% of patients were treated with antibiotics during hospitalization for an average of 2.7 weeks. Steroids were prescribed for 52% of patients and tumor necrosis factor alpha (TNF-alpha) antagonists for 17%. Surgical resection was required for 33 patients (44% of the cohort) while 51% were managed with antibiotics and/or percutaneous drainage. The most common surgical intervention was ileocecal resection (45%). Although patients who underwent follow-up imaging were more likely to require early surgical intervention (P = 0.04), no statistically significant predictor of surgery could be identified from this cohort. Time to surgery varied numerically according to abscess size (HR = 1.18, 95% CI = 0.62-2.27, P = 0.61). CONCLUSIONS: Although the majority of patients with CD-related intra-abdominal collections underwent surgical resection in this cohort, no obvious predictors of surgical intervention could be identified. The decision to perform early surgery appeared to be influenced by the findings observed on cross-sectional imaging during the follow-up of these collections.

COVID-19 and endoscopy services in intermediately affected countries: a position statement from the saudi gastroenterology association.

With the global pandemic due to coronavirus disease 2019 (COVID-19), there has been a significant strain on healthcare facilities. The infectivity rate, as well as the rate of healthcare workers who have fallen ill to the disease, has raised concerns globally on the proper management of patients as well as the role of safe healthcare provision utilizing personal protective equipment (PPE). Furthermore, the limited supply of PPEs has mandated rationing their use to achieve maximum utility and preservation. Multiple gastroenterology associations have issued guidance and statements that would help healthcare providers in navigating these unprecedented and difficult times, and the Saudi Gastroenterology Association has provided this statement in an effort to bring the most up to date information for the management of endoscopy units in terms of resources, manpower planning, scheduling, as well as infection control policies and leadership.

Frequent Activation of Notch Signaling Pathway in Colorectal Cancers and Its Implication in Patient Survival Outcome.

Colorectal cancer is a major health concern as it ranks third in incidence and second major cause of cancer-related deaths worldwide. A leading cause of treatment failure has been attributed to cancer stem cells that can invariably resist existing chemotherapeutic regimens. Notch signaling pathway has been involved in the maintenance of stem cells besides being crucial in cell fate decision and embryonic development. This pathway has also been implicated in several human malignancies including colorectal cancer. We investigated mRNA expression of four Notch receptors (Notch1-4), five ligands (Jag1, Jag2, Dll1, Dll3, and Dll4), and four target genes (Hes1, Hes5, Hey1, and Hey2) using highly specific TaqMan gene expression assays in colorectal adenomas and cancers. Upregulated expression of Notch receptors ranged between 29 and 73% in colorectal cancers and between 11 and 56% in adenomas. Expression of Notch3 and Notch4 receptors was significantly higher in colorectal cancers compared to normal and adenoma tissues. The Jagged and Delta-like ligands were overexpressed between 25 and 52% in colorectal cancers, while in adenomas, it ranged between 0 and 33%. Combining the data for upregulation of receptors and ligands suggests that 86% colorectal cancers and 56% adenomas exhibited overexpression of Notch pathway genes in our cohort. Notch target genes were upregulated between 24 and 33% in colorectal cancers and between 11 and 22% in adenomas. Collating upregulation of Notch receptors and ligands with the target genes showed concordance in 58% colorectal tumors. Additionally, we evaluated expression of Notch receptors, ligands, and target genes with prognosis using the TCGA mRNA expression dataset. Patients overexpressing Notch3, Notch4, and Hey1 had significantly poorer overall survival relative to those having lower levels of these genes. Taken together, Notch signaling components are aberrantly overexpressed in colorectal tumors, and development of therapeutics targeting the Notch pathway may prove to be beneficial in the management of colorectal cancers.

Drug utilization and cost associated with inflammatory bowel disease management in Saudi Arabia.

BACKGROUND: There has been an increase in incidence and prevalence of inflammatory bowel disease (IBD) outside the western countries. Treatment costs are an essential component for healthcare planning and priority setting. The utilization patterns and annual administration and cost of IBD medications are largely unknown in countries with an increasing incidence of disease, Saudi Arabia being an example. AIM: To evaluate the use of non-biologic and biologic agents and their associated annual administration costs in a sample of patients with Crohn's disease (CD) and ulcerative colitis (UC) in Saudi Arabia. METHODS: Single-center retrospective chart review was performed to determine the use of biologic and non-biologic medications among IBD patients in a tertiary care hospital in Riyadh, Saudi Arabia. Daily and the annual acquisition cost of different IBD therapeutic agents was calculated. The utilization rates and cost of each type of medication by CD and UC patients were compared. RESULTS: Data of 258 CD patients and 249 UC patients were analyzed. Infliximab and adalimumab were the most commonly prescribed biologics among the study sample, however, their utilization rates were significantly higher among CD than UC patients (36.82% vs. 11.24%, and 20.54% vs. 9.64%, respectively, P < 0. 01). Azathioprine utilization rate was also higher among CD patients compared to their UC counterparts (71.71% vs. 40.16%, respectively, P < 0.01). However, the utilization rate of mesalazine in the UC patients was significantly higher than their CD counterparts (85.53% vs. 14.34% for CD, P < 0.01). The annual cost of biologics (including administration and lab test cost) ranged from 5572 USD for ustekinumab to 18,424 USD for vedolizumab. On the other hand, the annual cost of non-biologics ranged from 16 USD for prednisone to 527 USD for methotrexate. CONCLUSION: Biologics are extensively used in the management of IBD, particularly CD, and their utilization costs are significantly higher than non-biologics. Future studies should examine the cost effectiveness of IBD medications especially in countries with increasing incidence such as Saudi Arabia.

Pancreatic tuberculosis in immunocompetent patients. At the University Hospital in Kingdom of Saudi Arabia.

OBJECTIVES: To raise awareness of practitioners on benign treatable conditions such as pancreatic tuberculosis (TB). Methods: A retrospective study at King Khaled University Hospital, Riyadh, Saudi Arabia of all patient charts presented with pancreatic mass for a period of 10 years (2007-2017) with a study duration of 4 years between 2013 and 2017. Patients with confirmed diagnosis of pancreatic cancer were excluded. A written ethical approval was obtained accordingly. Results: All adult patient charts were retrospectively reviewed with a pancreatic mass for a period of 10 years (2007-2017). Nine patients were identified with proven diagnosis of TB. The data were obtained based on demographic features, sign and symptoms, duration of illness, imaging, ultrasound, contrast enhanced computed tomography scan, cytology or histopathology, polymerase chain reaction, culture and follow up with anti-tuberculous therapy and samples for cytology or histology. The histological findings of granuloma with caseation or positive culture were used confirming the diagnosis of TB. All patients were immunocompetent and screened for human immunodeficiency viruses before starting anti-TB treatment. Results were negative. All patients who underwent fine needle aspiration (FNA) and endoscopic ultrasound (EUS) for suspicious pancreatic mass were provided trial of antibiotics as cases of pancreatic tuberculosis showed dramatic improvement during follow up and cured from the disease. Conclusion: The EUS and FNA are good tools to confirm malignancy and rule out benign treatable conditions like TB for any patient with a pancreatic mass suspicious for carcinoma.

Genetic variants in the WNT signaling pathway are protectively associated with colorectal cancer in a Saudi population.

The Wnt/ß-catenin signaling pathway has been etiologically implicated in the development and progression of colorectal cancer. We studied thirteen single nucleotide polymorphisms (SNPs) located in SFRP3 (rs7775), CTNNB1 (ß-catenin) [rs4135385, rs13072632], APC (rs454886, rs459552), LRP6 (rs2075241, rs2284396), DKK4 (rs3763511), DKK3 (rs6485350), TCF4 (rs12255372) and AXIN2 (rs3923086, rs3923087, rs4791171) in patients with colorectal cancer (n = 122) and controls (n = 110). Evaluation of WNT pathway SNPs showed protective association for rs4135385, located in ß-catenin. Additionally, variants in SFRP3 (rs7775) and LRP6 (rs2284396) which did not show any association in the overall analysis were significantly associated with female and old aged colorectal cancer patients, respectively.

Association between polymorphisms in PRNCR1 and risk of colorectal cancer in the Saudi population.

LncRNA Prostate cancer non-coding RNA (PRNCR1) is downregulated in many types of cancer. The current case-control study was performed on 144 patients with colorectal cancer and 130 matching controls. Genotyping was performed using TaqMan assays for four Single Nucleotide Polymorphisms (SNPs) in PRNCR1. RNAsnp Web Server was used to detect variations in the secondary structure for each SNP. The genotyping analysis for SNP rs1456315 showed increased association with colorectal cancer with the homozygous CC variant allele (OR: 2.09; χ2 = 4.95; CI: 1.08-4.02; p = 0.02), the minor allele frequency, and additive genotype, respectively (OR: 1.55; χ2 = 6.24; CI: 1.09-2.19; p = 0.01) & (OR: 1.64; χ2 = 4.04; CI: 1.01-2.67; p = 0.04). A risk association was also observed among younger age patients (≤57) and in female patients as well as in patients with tumors of the colon. For the other SNPs tested (rs16901946, rs13252298, rs1016343), no significant association was observed. The secondary structure of the rs1456315 mutant is different from that of the wild-type. Our findings suggest that the upregulation of PRNCR1 and its variants is associated with increased risk of colorectal cancer in Saudi patients, indicating that PRNCR1 might be a unique and valuable signature for predicting the risk of colorectal cancer in a Saudi population.

Toll-like receptor 6 expression, sequence variants, and their association with colorectal cancer risk.

This is the first study to examine the potential correlation of the rs3796508 and rs5743810 SNPs of the TLR6 gene in patients with colorectal cancer (CRC) in a subset of the Saudi population. TLR6 gene expression was studied by real-time PCR assaysin 10 matching normal and cancer colon tissues. TLR6 expression at the protein level was determined by immunohistochemistry. A case-control search was conductedon 115 case patients and 102 controls. All samples were genotyped with the TaqMan assay for the TLR6 gene. Odds ratios and 95% confidence interval were computed from logistic regression models after adjusting for age, sex, and tumor localization. Our findings showed a decrease in TLR6 expression (p <0.001) in colon cancer tissues when compared to normal colon tissues. Global analysis revealed no significant association between the TLR6 rs3796508 and rs5743810 and CRC in this population. However, the Val/Met genotype of rs3796508 had a significantly higher frequency in the control group than in the cases for the male group (OR= 0.095, and p= 0.03385) or the volunteers aged more than 57 years OR= 0.152; and p= 0.04069, respectively). Two non-synonymous single nucleotide polymorphisms (SNP; S249P and V327M) were common in a few patients and were predicted as damaging by SIFT and Polyphen and were further analyzed for their protein stability and function using advanced bioinformatics tools. The results suggest that TLR6 rs3796508 has a crucial role as a protective factor against colorectal cancer in the older Saudi male population.

TDG Gene Polymorphisms and Their Possible Association with Colorectal Cancer: A Case Control Study.

Genetic alterations that might lead to colorectal cancer involve essential genes including those involved in DNA repair, inclusive of base excision repair (BER). Thymine DNA glycosylase (TDG) is one of the most well characterized BER genes that catalyzes the removal of thymine moieties from G/T mismatches and is also involved in many cellular functions, such as the regulation of gene expression, transcriptional coactivation, and the control of epigenetic DNA modification. Mutation of the TDG gene is implicated in carcinogenesis. In the present study, we aimed to investigate the association between TDG gene polymorphisms and their involvement in colon cancer susceptibility. One hundred blood samples were obtained from colorectal cancer patients and healthy controls for the genotyping of seven SNPs in the TDG gene. DNA was extracted from the blood, and the polymorphic sites (SNPs) rs4135113, rs4135050, rs4135066, rs3751209, rs1866074, and rs1882018 were investigated using TaqMan genotyping. One of the six TDG SNPs was associated with an increased risk of colon cancer. The AA genotype of the TDG SNP rs4135113 increased the risk of colon cancer development by more than 3.6-fold, whereas the minor allele A increased the risk by 1.6-fold. It also showed a 5-fold higher risk in patients over the age of 57. SNP rs1866074 showed a significant protective association in CRC patients. The GA genotype of TDG rs3751209 was associated with a decreased risk in males. There is a significant relationship between TDG gene function and colorectal cancer progression.

Predictors of failure of endoscopic retrograde cholangiography in clearing bile duct stone on the initial procedure.

BACKGROUND/AIMS: The aim of this study is to predict cases where the clearance of the biliary system from stones at the initial endoscopic retrograde cholangiopancreatography (ERCP) might be of value for better risk-stratifying patients. We attempted to identify factors that are associated with a higher failure rate of clearing the biliary system on the index ERCP. PATIENTS AND METHODS: This is a retrospective study from January 2008 to January 2015. All patients with bile duct stones confirmed on ERCP were included in this study. Patients who had prior attempts of bile duct stone extraction were excluded. RESULTS: A total of 554 ERCPs were performed to extract biliary duct stones from 426 patients. The mean age was 46.3 years and 41.7% were males. The group where the index ERCP did not clear the biliary system tended to be older (50.4 vs. 45.2 years, P = 0.03). On multivariate analysis, the presence of fever (OR 4.64; 95% CI, 1.66-12.79), a larger number of filling defects (OR 1.34; 95% CI, 1.13-1.93), presence of a stricture distal to a stone (OR 4.63; 95% CI, 1.36-15.78), the use of an extraction basket (OR 3.23; 95% CI, 1.56-6.74), and/or mechanical lithotripsy (OR 3.05; 95% CI, 1.10-8.49) were all associated with a lower odds of clearing the biliary system. The use of an extraction balloon was associated with the success of clearing the biliary system (99.7% vs. 77.4%, P < 0.01) and a lower odds of failing (OR 0.01; 95% CI, 0.00-0.08) on multivariate analysis. CONCLUSION: A few of the characteristics that are found on cholangiography at the index ERCP could be used to identify patients that might require more than one ERCP to clear the biliary system from stones.

Findings during screening colonoscopies in a Middle Eastern cohort.

BACKGROUND/AIMS: Colorectal cancer is the most common cancer in males and the third most common cancer in females. We aim to determine the polyp and adenoma prevalence in a cohort of patients who underwent opportunistic screening colonoscopies. PATIENTS AND METHODS: A retrospective cohort study was conducted using an endoscopic reporting database of individuals seen at three tertiary care hospitals (two public hospitals and one private) in Riyadh, Saudi Arabia. Consecutive patients who were 45 years of age and older and underwent opportunistic screening colonoscopies between November 2016 and October 2017 were included. We excluded those with a history of colon cancer or colonic resection for any reason, inflammatory bowel disease, gastrointestinal bleeding, or anemia. RESULTS: Around 1180 patients were included in the study with a mean age of 58.6 years (SD = 7.3), with males representing 53.6% and an overall cecal intubation rate of 92.4%. Masses were found in 1.6% of the study population (50% in the sigmoid or rectosigmoid, 37.5% in the rectum). The polyp detection rate in colonoscopies was 24.8% and the adenoma detection rate was 16.8%. The histology of removed polyps was tubular adenomas in 56.6%, hyperplastic polyps in 32.7%, tubulovillous adenomas in 8.2%, and villous adenomas in 2.5%. The majority of the polyps were in the sigmoid colon (28.3%) and rectum (22.0%), followed by the ascending colon (11.2%) and cecum (10.3%), then the transverse colon and descending colon (9.4% each), and multiple locations in the remainder. CONCLUSION: The prevalence of polyps and adenomas in this cohort is less than that reported in the Western populations.

Potential role of Toll-like receptor 2 expression and polymorphisms in colon cancer susceptibility in the Saudi Arabian population.

BACKGROUND: Inflammation is a fundamental factor that contributes to the development and progression of several types of cancer including colon cancer. Toll-like receptors (TLRs) and their signaling pathways have been reported to be associated with chronic inflammation and thereby induced cancer. Our aim was to investigate the expression and polymorphisms of TLR2 and their association with colon cancer. METHODS: Real-time PCR and immunohistochemistry were used to investigate TLR2 gene expression and to evaluate the potential risk of predisposition to colon cancer caused by three tagging single-nucleotide polymorphisms (SNPs) on TLR2, including rs3804100, rs4696480, and rs3804099. TaqMan assay was conducted on samples from 115 patients with colon cancer and 102 age- and sex-matched normal individuals. RESULTS: We found that, TLR2 was highly expressed in epithelial colon cancer cells and both TLR2 mRNA and protein levels, and significantly decreased in tumor tissues compared to normal tissues. Two of three TLR2 SNPs increased the risk of colon cancer. However, TLR2 rs3804099 increased the risk of colon cancer development by more than 3.8- and 5-fold in female patients and patients aged less than 57 years, respectively. The T allele of TLR2 rs3804100 showed a significant association with patients less than 57 years. In silico analysis of the TLR2 nucleotide substitution in SNP rs3804100 and rs3804099 determined that 67% and 70% probability of these single nucleotide variants alter splicing phenotypes, rs3804100 more specifically result on activating an additional splice site. Genotype and allele frequencies of rs4696480 were similar between the overall study populations. Thus, TLR2 rs4696480 appear to be not involved in colon cancer in our study population. CONCLUSIONS: There was a significant link between innate immunity deregulation through disruption of the TLRs and potential development of colon cancer. These SNPs can be used as screening markers for predicting colon cancer risk earlier in life to implement necessary prevention.

The expression of telomere-related proteins and DNA damage response and their association with telomere length in colorectal cancer in Saudi patients.

BACKGROUND: Colorectal cancer is the leading cause of cancer-related deaths in Saudi Arabia. Cancer has a multifactorial nature and can be described as a disease of altered gene expression. The profiling of gene expression has been used to identify cancer subtypes and to predict patients' responsiveness. Telomere-associated proteins that regulate telomere biology are essential molecules in cancer development. Thus, the present study examined their contributions to colorectal cancer progression in Saudi patients. METHODS: The expression of hTERT, TRF1, TRF2, POT1, ATR, ATM, Chk1 and Chk2 were measured via real-time PCR in matched cancerous and adjacent tissues of CRC patients. The protein level of hTERT, TRF1, TRF2, ATR, ATM, Chk1 and Chk2 were measured using immunohistochemistry. A region of hTERT core promoter was sequenced via Sanger sequencing. Methylation of CTCF binding site was examined via methylation-specific PCR. Finally, the length of telomere was estimated using q-PCR. RESULTS: Our results showed that POT1, ATR, Chk1 and Chk2 show increased expression in CRC relative to the adjacent mucosa. The expression levels of each gene were associated with clinicopathological characteristics of patients with CRC. There was a positive correlation between the age of the patients and hTERT expression. Regarding tumor site, telomere length, ATR, ATM and Chk1 were shown to be altered. No somatic mutation was detected in hTERT core promoter, and no differences in methylation patterns at CTCF binding site in the promoter between normal and cancer tissues. CONCLUSION: Analysis of targeted genes expression in colorectal cancer based on the clinical variables revealed that tumor location and age could have a role in gene expression and telomere length variations and this could be taken under consideration during CRC diagnosis and therapy. Other epigenetic mechanisms could influence hTERT expression in cancers. Our findings warrant further validation through experiments involving a larger number of patients.

Policy of screening for colorectal cancer in Saudi Arabia: A prospective analysis.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Several policies of CRC screening are available in different countries. The idea of screening is to identify patients at risk by detection of precancerous and small cancers early enough before they become advanced. In Saudi Arabia (SA), there is no countrywide policy for CRC screening despite the increasing incidence of the disease. Screening for CRC is a multidisciplinary approach that requires education programs, substantial financial support, several logistic measures, and predetermined resources before implementing such a program. We performed a prospective and systematic analysis of the of the screening policy of CRC in SA in view of high demand, anticipated development, and implementation of such a policy in the near future. We also attempted to investigate the justification for developing such a policy, as well as the difficulties, barriers, and opportunities that may be faced in its implementation. Further, we highlighted the current view of similar international screening policies. In this analysis, we adopted the framework for health policy analysis that examines four areas which may affect policy development, namely; content, context, process and actors.

Plasma ghrelin and leptin in patients with inflammatory bowel disease and its association with nutritional status.

BACKGROUND/AIMS: Ghrelin and leptin are thought to play a role in the loss of appetite in active inflammatory bowel disease (IBD). This study seeks to probe into the association of these markers with regards to IBD and the nutritional status of these patients. A case-control study was conducted between May 2015 and March 2016 at King Khalid University Hospital (KKUH). Thirty-one patients with IBD (both active and non-active) and forty-one healthy controls (both non-fasting and fasting) were recruited. PATIENTS AND METHODS: Plasma ghrelin and leptin levels were determined using an enzyme immunoassay (EIA) technique. The nutritional status was determined through the standardized Mini-Nutritional Assessment (MNA) questionnaire. RESULTS: The difference in the plasma ghrelin between active (263.7 pg/mL) and non-active (108 pg/mL) cases was significant (P= 0.02). The difference in mean plasma leptin level between active cases (229.4 pg/mL) vs. non-active cases (359.7 pg/mL) was insignificant (P= 0.4). In fasting (2028.6 pg/mL) and non-fasting controls (438.8 pg/mL), the mean plasma ghrelin values was significantly different (P< 0.01). In contrast, the plasma leptin level difference between fasting (727.3 pg/mL) and non-fasting (577 pg/mL) controls was insignificant (P= 0.14). There is a statistically significant association in mean ghrelin levels between the case group and the control group (P< 0.01). With regards to nutritional status, the mean MNA score of active cases compared to fasting controls was 18.8 ± 5 vs. 20.8 ± 3.8, respectively (P< 0.01) Conclusion: Ghrelin levels were lower in the active IBD cases compared to the inactive ones, signifying an underlying pathology as etiology to this phenomenon. Furthermore, ghrelin levels were significantly lower in both case groups compared to the controls. These findings, along with the disparity in the MNA scores, insinuate a possible link between hormone levels and the loss of appetite from which these patients suffer.