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Article ; Online: Evidence of Association between CTLA-4 Gene Polymorphisms and Colorectal Cancers in Saudi Patients

Al-Harbi, Nouf / Abdulla, Maha-Hamadien / Vaali-Mohammed, Mansoor-Ali / Bin Traiki, Thamer / Alswayyed, Mohammed / Al-Obeed, Omar / Abid, Islem / Al-Omar, Suliman / Mansour, Lamjed

Genes (Basel). 2023 Apr. 06, v. 14, no. 4

2023

Abstract: Cytotoxic T lymphocyte antigen-4 (CTLA-4) has been identified as an immunosuppressive molecule involved in the negative regulation of T cells. It is highly expressed in several types of autoimmune diseases and cancers including colorectal cancer (CRC). ( ... ...

Abstract	Cytotoxic T lymphocyte antigen-4 (CTLA-4) has been identified as an immunosuppressive molecule involved in the negative regulation of T cells. It is highly expressed in several types of autoimmune diseases and cancers including colorectal cancer (CRC). (1) Objective: To explore the association between CTLA-4 single nucleotide polymorphisms (SNP) and risk to (CRC) in the Saudi population. (2) Methods: In this case-control study, 100 patients with CRC and 100 matched healthy controls were genotyped for three CTLA-4 SNPs: rs11571317 (−658C > T), rs231775 (+49A > G) and rs3087243 (CT60 G > A), using TaqMan assay method. Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (95% CIs) for five inheritance models (co-dominant, dominant, recessive, over-dominant and log-additive). Furthermore, CTLA-4 expression levels were evaluated using quantitative real-time PCR (Q-RT-PCR) in colon cancer and adjacent colon tissues. (3) Results: Our result showed a significant association of the G allele (OR = 2.337, p < 0.0001) and GG genotype of the missense SNP +49A > G with increased risk of developing CRC in codominant (OR = 8.93, p < 0.0001) and recessive (OR = 16.32, p < 0.0001) models. Inversely, the AG genotype was significantly associated with decreased risk to CRC in the codominant model (OR = 0.23, p < 0.0001). In addition, the CT60 G > A polymorphism exhibited a strong association with a high risk of developing CRC for the AA genotype in codominant (OR = 3.323, p = 0.0053) and in allele models (OR = 1.816, p = 0.005). No significant association was found between −658C > T and CRC. The haplotype analysis showed that the G-A-G haplotype of the rs11571317, rs231775 and rs3087243 was associated with high risk for CRC (OR = 57.66; p < 0.001). The CTLA-4 mRNA gene expression was found significantly higher in tumors compared to normal adjacent colon samples (p < 0.001). (4) Conclusions: Our findings support an association between the CTLA-4 rs231775 (+49A > G) and rs3087243 (CT60 G > A) polymorphisms and CRC risk in the Saudi population. Further validation in a larger cohort size is needed prior to utilizing these SNPs as a potential screening marker in the Saudi population.
Keywords	T-lymphocytes ; alleles ; case-control studies ; colon ; colorectal neoplasms ; cytotoxicity ; gene expression ; genotyping ; haplotypes ; immunosuppression ; models ; quantitative polymerase chain reaction ; risk ; risk reduction
Language	English
Dates of publication	2023-0406
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14040874
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Surveillance Compliance and Quality of Life Assessment Among Surgical Patients with Familial Adenomatous Polyposis Syndrome.

Alhassan, Noura / Helmi, Hadeel / Alzamil, Abdullah / Alshammari, Afraj / Altamimi, Atheer / Alshammari, Sulaiman / Bin Traiki, Thamer / Albanyan, Saleh / AlKhayal, Khayal / Zubaidi, Ahmad / Al-Obeed, Omar

Journal of epidemiology and global health

2024 Volume 14, Issue 1, Page(s) 86–93

Abstract: Background: Familial adenomatous polyposis (FAP) syndrome has a near-100% lifetime risk of colorectal cancer. Early surveillance and prophylactic surgery have been advocated to reduce this risk. However, the surveillance practices among FAP individuals ... ...

Abstract	Background: Familial adenomatous polyposis (FAP) syndrome has a near-100% lifetime risk of colorectal cancer. Early surveillance and prophylactic surgery have been advocated to reduce this risk. However, the surveillance practices among FAP individuals in Saudi Arabia are unknown. We aimed to explore surveillance compliance in our population, as well as the disease impact on their quality of life (QoL). Methods: All patients with FAP who underwent surgical resection at King Saud University Medical City between 2016 and 2022 were included. Demographic data, clinical features, family history, and compliance with surveillance were collected and analyzed. QoL questionnaires: Short-form health survey (SF-36) and European Organization for Research and Treatment (EORTC) were conducted by phone interview. Results: A total of 14 patients were included with an average age of 25 years. Three patients (21.4%) were the first of their family members to develop FAP. Nine patients (64%) were untested for genetic mutation due to lack of referral to geneticists. The compliance rate toward both pre-operative colonoscopy and upper endoscopy were 78%. However, 38% and 27% compliance rates were observed toward initial and post-operative colonoscopy, respectively. The compliance rate was 14% toward thyroid ultrasound. QoL scores varied among patients, with a mean score above 60 across all SF-36 domains. Conclusion: An overall poor compliance was observed among our participants, particularly toward thyroid ultrasound. Increased health awareness and patient education are essential. In addition, the importance of surveillance and genetic counseling should be emphasized among physicians treating these patients.
MeSH term(s)	Humans ; Adenomatous Polyposis Coli/surgery ; Adenomatous Polyposis Coli/psychology ; Adenomatous Polyposis Coli/diagnosis ; Quality of Life ; Male ; Female ; Adult ; Saudi Arabia/epidemiology ; Patient Compliance/statistics & numerical data ; Patient Compliance/psychology ; Young Adult ; Middle Aged ; Surveys and Questionnaires ; Colonoscopy/statistics & numerical data ; Colonoscopy/psychology ; Adolescent ; Population Surveillance/methods
Language	English
Publishing date	2024-01-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2645324-1
ISSN	2210-6014 ; 2210-6014
ISSN (online)	2210-6014
ISSN	2210-6014
DOI	10.1007/s44197-023-00171-8
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Article ; Online: Pneumomediastinum following anastomotic leakage in colon surgery: a case report and literature review.

Al Obeed, Omar A

Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association

2014 Volume 20, Issue 6, Page(s) 383–384

Abstract: We are presenting the case of a 62-year-old woman who developed a pneumomediastinum as a complication of anastomotic leakage (AL) following laparoscopic sigmoid resection due to diverticulitis. The patient presented with retroperitoneal air, ... ...

Abstract	We are presenting the case of a 62-year-old woman who developed a pneumomediastinum as a complication of anastomotic leakage (AL) following laparoscopic sigmoid resection due to diverticulitis. The patient presented with retroperitoneal air, pneumomediastinum, emphysematous gall bladder, air in the wall of stomach, and proximal small bowel. There were a few tiny air bubbles around the anastomosis. We discuss this unusual clinical presentation of intraperitoneal and extraperitoneal air as a presenting sign of AL.
MeSH term(s)	Anastomotic Leak/diagnosis ; Anastomotic Leak/surgery ; Colectomy/adverse effects ; Colon, Sigmoid/surgery ; Diverticulitis, Colonic/surgery ; Female ; Humans ; Laparoscopy/methods ; Mediastinal Emphysema/diagnosis ; Mediastinal Emphysema/etiology ; Mediastinal Emphysema/surgery ; Middle Aged ; Reoperation ; Tomography, X-Ray Computed
Language	English
Publishing date	2014-11-28
Publishing country	India
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	2299174-8
ISSN	1998-4049 ; 1319-3767
ISSN (online)	1998-4049
ISSN	1319-3767
DOI	10.4103/1319-3767.145332
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Article ; Online: Factors Associated with Statin Discontinuation Following Metabolic and Bariatric Surgery: A Retrospective Analysis of 2012-2021 Electronic Medical Records Network Data.

Alsuhibani, Abdulrahman A / Al-Obeed, Omar A / Wigle, Patricia R / Alsultan, Mohammed M / Guo, Jeff J / Lin, Alex C / Rao, Marepalli B / Hincapie, Ana L

Obesity surgery

2024 Volume 34, Issue 4, Page(s) 1267–1278

Abstract: Background: Bariatric surgery has been shown to improve hyperlipidemia, decreasing the need for statin medications. Although maintaining statin therapy post-surgery for those with a history of atherosclerotic cardiovascular disease (ASCVD) is advised, ... ...

Abstract	Background: Bariatric surgery has been shown to improve hyperlipidemia, decreasing the need for statin medications. Although maintaining statin therapy post-surgery for those with a history of atherosclerotic cardiovascular disease (ASCVD) is advised, it is uncertain if discontinuation risks differ between those with and without ASCVD history. Aim: The study aims to analyze the rate and reasons for statin cessation post-bariatric surgery in the US using real-world data. Methods: Using the TriNetX electronic medical records network from 2012 to 2021, the study involved patients aged 18 or older on statins at the time of bariatric surgery. They were categorized into primary and secondary prevention groups based on prior ASCVD. Statin discontinuation was defined as a 90-day gap post the last statin dosage. The Cox model assessed factors influencing statin cessation. Results: Seven hundred and thirty-three statin users undergoing bariatric surgery were identified, with 564 (77%) in primary prevention. Six months post-surgery, 48% of primary prevention patients and 34.5% of secondary ones stopped statins. Primary prevention patients had a 30% higher likelihood of cessation compared to secondary prevention (hazard ratio, 1.30; 95% CI, 1.06-1.60) as shown by multivariable analysis. Conclusions: Post-bariatric surgery, primary prevention patients are more likely to discontinue statins than secondary prevention patients.
MeSH term(s)	Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Retrospective Studies ; Electronic Health Records ; Obesity, Morbid/surgery ; Bariatric Surgery ; Atherosclerosis ; Cardiovascular Diseases/prevention & control
Chemical Substances	Hydroxymethylglutaryl-CoA Reductase Inhibitors
Language	English
Publishing date	2024-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	1070827-3
ISSN	1708-0428 ; 0960-8923
ISSN (online)	1708-0428
ISSN	0960-8923
DOI	10.1007/s11695-024-07110-x
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Article ; Online: Emerging trends in colorectal cancer: Dysregulated signaling pathways (Review).

Ahmad, Rehan / Singh, Jaikee Kumar / Wunnava, Amoolya / Al-Obeed, Omar / Abdulla, Maha / Srivastava, Sandeep Kumar

International journal of molecular medicine

2021 Volume 47, Issue 3

Abstract: Colorectal cancer (CRC) is the third most frequently detected type of cancer, and the second most common cause of cancer‑related mortality globally. The American Cancer Society predicted that approximately 147,950 individuals would be diagnosed with CRC, ...

Abstract	Colorectal cancer (CRC) is the third most frequently detected type of cancer, and the second most common cause of cancer‑related mortality globally. The American Cancer Society predicted that approximately 147,950 individuals would be diagnosed with CRC, out of which 53,200 individuals would succumb to the disease in the USA alone in 2020. CRC‑related mortality ranks third among both males and females in the USA. CRC arises from 3 major pathways: i) The adenoma‑carcinoma sequence; ii) serrated pathway; and iii) the inflammatory pathway. The majority of cases of CRC are sporadic and result from risk factors, such as a sedentary lifestyle, obesity, processed diets, alcohol consumption and smoking. CRC is also a common preventable cancer. With widespread CRC screening, the incidence and mortality from CRC have decreased in developed countries. However, over the past few decades, CRC cases and mortality have been on the rise in young adults (age, <50 years). In addition, CRC cases are increasing in developing countries with a low gross domestic product (GDP) due to lifestyle changes. CRC is an etiologically heterogeneous disease classified by tumor location and alterations in global gene expression. Accumulating genetic and epigenetic perturbations and aberrations over time in tumor suppressor genes, oncogenes and DNA mismatch repair genes could be a precursor to the onset of colorectal cancer. CRC can be divided as sporadic, familial, and inherited depending on the origin of the mutation. Germline mutations in APC and MLH1 have been proven to play an etiological role, resulting in the predisposition of individuals to CRC. Genetic alterations cause the dysregulation of signaling pathways leading to drug resistance, the inhibition of apoptosis and the induction of proliferation, invasion and migration, resulting in CRC development and metastasis. Timely detection and effective precision therapies based on the present knowledge of CRC is essential for successful treatment and patient survival. The present review presents the CRC incidence, risk factors, dysregulated signaling pathways and targeted therapies.
MeSH term(s)	Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; DNA Mismatch Repair ; Early Detection of Cancer ; Germ-Line Mutation ; Humans ; Signal Transduction
Language	English
Publishing date	2021-01-07
Publishing country	Greece
Document type	Journal Article
ZDB-ID	1444428-8
ISSN	1791-244X ; 1107-3756
ISSN (online)	1791-244X
ISSN	1107-3756
DOI	10.3892/ijmm.2021.4847
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Article: A Constitutional Mismatch Repair Deficiency Syndrome Presented With an Advanced Rectal Cancer in a Juvenile Female: A Case Report and Literature Review.

AlAli, Mohammed N / Zikry, Abdulrahman H / AlShammari, Sulaiman A / Zayed, Mohammed Ayesh / Alswayyed, Mohammed / AlObeed, Omar A

Cureus

2022 Volume 14, Issue 4, Page(s) e24615

Abstract: The constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and challenging condition with a poor prognosis. It results from biallelic mismatch repair gene mutations and leads to multiorgan cancers. Therefore, we report the first case of ... ...

Abstract	The constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and challenging condition with a poor prognosis. It results from biallelic mismatch repair gene mutations and leads to multiorgan cancers. Therefore, we report the first case of advanced juvenile rectal cancer related to CMMRD syndrome in the Gulf region. She is a 13-year-old female, born to non-consanguineous parents with a positive family history of malignancy, presented with an eight-month history of a retractable bulging anal mass associated with diarrhea mixed with blood and constitutional symptoms. She was cachectic with café au lait spots all over her body. Upon investigation, she was found to have invasive rectal adenocarcinoma. The case was started on neoadjuvant chemoradiotherapy in addition to genetic testing which showed a homozygous pathogenic variant in PMS2, indicating CMMRD syndrome. The patient underwent pre-operative post-neoadjuvant reassessment followed by laparoscopic total proctocolectomy with ileal J-pouch creation and ileoanal anastomosis with temporary diverting loop ileostomy which later on was reversed with no complications or recurrence. The family declined to continue the adjuvant therapy but accepted the surveillance programs and genetic testing. Unusual or late presentation secondary to a very rare syndrome like CMMRD is a major challenge to clinicians, hence a high index of suspicion and proper utilization of genetics programs might be the best available solutions.
Language	English
Publishing date	2022-04-30
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.24615
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Article ; Online: Rs10204525 Polymorphism of the Programmed Death (PD-1) Gene Is Associated with Increased Risk in a Saudi Arabian Population with Colorectal Cancer.

Al-Harbi, Nouf / Vaali-Mohammed, Mansoor-Ali / Al-Omar, Suliman / Zubaidi, Ahmed / Al-Obeed, Omar / Abdulla, Maha-Hamadien / Mansour, Lamjed

Medicina (Kaunas, Lithuania)

2022 Volume 58, Issue 10

Abstract: Checkpoint programmed death-1 (PD-1) has been identified as an immunosuppressive molecule implicated in the immune evasion of transformed cells. It is highly expressed in tumor cells in order to evade host immunosurveillance. In this study, we aimed to ... ...

Abstract	Checkpoint programmed death-1 (PD-1) has been identified as an immunosuppressive molecule implicated in the immune evasion of transformed cells. It is highly expressed in tumor cells in order to evade host immunosurveillance. In this study, we aimed to assess the association between single nucleotide polymorphisms (SNP) of
MeSH term(s)	Humans ; Asians ; Case-Control Studies ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Genetic Predisposition to Disease/genetics ; Genotype ; Polymorphism, Single Nucleotide/genetics ; Programmed Cell Death 1 Receptor/genetics ; Saudi Arabia/epidemiology
Chemical Substances	Programmed Cell Death 1 Receptor ; PDCD1 protein, human
Language	English
Publishing date	2022-10-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2188113-3
ISSN	1648-9144 ; 1010-660X
ISSN (online)	1648-9144
ISSN	1010-660X
DOI	10.3390/medicina58101439
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Article ; Online: Evidence of Association between CTLA-4 Gene Polymorphisms and Colorectal Cancers in Saudi Patients.

Al-Harbi, Nouf / Abdulla, Maha-Hamadien / Vaali-Mohammed, Mansoor-Ali / Bin Traiki, Thamer / Alswayyed, Mohammed / Al-Obeed, Omar / Abid, Islem / Al-Omar, Suliman / Mansour, Lamjed

Genes

2023 Volume 14, Issue 4

Abstract	Cytotoxic T lymphocyte antigen-4 (CTLA-4) has been identified as an immunosuppressive molecule involved in the negative regulation of T cells. It is highly expressed in several types of autoimmune diseases and cancers including colorectal cancer (CRC). (1)
MeSH term(s)	Humans ; CTLA-4 Antigen/genetics ; Genetic Predisposition to Disease ; Case-Control Studies ; Saudi Arabia/epidemiology ; Polymorphism, Single Nucleotide ; Colorectal Neoplasms/genetics
Chemical Substances	CTLA-4 Antigen
Language	English
Publishing date	2023-04-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14040874
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Article ; Online: 5-year oncological outcomes in left-sided malignant colonic obstruction: stent as bridge to surgery.

Alhassan, Noura S / AlShammari, Sulaiman A / AlRabah, Razan N / AlZahrani, Amirah M / Abdulla, Maha-Hamadien / Traiki, Thamer A Bin / Zubaidi, Ahmad M / Al-Obeed, Omar A / Alkhayal, Khayal A

BMC gastroenterology

2023 Volume 23, Issue 1, Page(s) 262

Abstract: Background: A considerable number of patients with colon cancer present with a colonic obstruction. The use of self-expanding metallic stents (SEMS) as a bridge to surgery (BTS) in potential curative patients with left-sided colonic cancer obstruction ... ...

Abstract	Background: A considerable number of patients with colon cancer present with a colonic obstruction. The use of self-expanding metallic stents (SEMS) as a bridge to surgery (BTS) in potential curative patients with left-sided colonic cancer obstruction remains debatable. Therefore, this study aimed to investigate the 5-year oncological outcomes of using a SEMS as a BTS. Methods: All patients with left-sided malignant colon obstruction who underwent curative surgery with no metastasis upon presentation between March 2009 and May 2013 were retrospectively reviewed and analyzed. Results: A total of 45 patients were included, 28 patients underwent upfront surgery, and 17 patients had a stent as a bridge to surgery. T4 stage was statistically significantly higher in patients who had a SEMS as a BTS (35.3% vs. 10.7%) (p-value 0.043). The mean duration in days of the SEMS to surgery was 13.76 (SD 10.08). TNM stage 3 was a prognostic factor toward distant metastasis (HR 5.05). When comparing patients who had upfront surgery to those who had a SEMS as a BTS, higher 5-year disease-free survival (75% vs. 72%) and 5-year overall survival (89% vs. 82%) were seen in patients who had upfront surgery. However, both were statistically insignificant. Conclusion: Using self-expanding metallic stents as a bridge to surgery yields comparable 5-year survival and disease-free survival rates to upfront emergency surgery. The decision to use SEMS versus opting for emergency surgery should be made after careful patient selection and with the assistance of experienced endoscopists. Trial registration: N/A.
MeSH term(s)	Humans ; Retrospective Studies ; Self Expandable Metallic Stents ; Intestinal Obstruction/etiology ; Intestinal Obstruction/surgery ; Colonic Neoplasms/complications ; Colonic Neoplasms/surgery ; Stents ; Treatment Outcome ; Colorectal Neoplasms/complications ; Colorectal Neoplasms/surgery
Language	English
Publishing date	2023-07-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2041351-8
ISSN	1471-230X ; 1471-230X
ISSN (online)	1471-230X
ISSN	1471-230X
DOI	10.1186/s12876-023-02903-3
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Article ; Online: Oncological outcomes of elective versus emergency surgery for colon cancer: A tertiary academic center experience.

Bin Traiki, Thamer A / AlShammari, Sulaiman A / AlRabah, Razan N / AlZahrani, Amirah M / Alshenaifi, Saud T / Alhassan, Noura S / Abdulla, Maha-Hamadien / Zubaidi, Ahmad M / Al-Obeed, Omar A / Alkhayal, Khayal A

Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association

2023 Volume 29, Issue 5, Page(s) 316–322

Abstract: Background: In this study, we aimed to identify the oncological outcomes in colon cancer patients who underwent elective versus emergency curative resection.: Methods: All patients who underwent curative resection for colon cancer between July 2015 ... ...

Abstract	Background: In this study, we aimed to identify the oncological outcomes in colon cancer patients who underwent elective versus emergency curative resection. Methods: All patients who underwent curative resection for colon cancer between July 2015 and December 2019 were retrospectively reviewed and analyzed. Patients were divided into two groups based on the presentation into elective and emergency groups. Results: A total of 215 patients with colon cancer were admitted and underwent curative surgical resection. Of those, 145 patients (67.4%) were elective cases, and 70 (32.5%) were emergency cases. Family history of malignancy was positive in 44 patients (20.5%) and significantly more common in the emergency group (P = 0.016). The emergency group had higher T and TNM stages (P = 0.001). The 3-year survival rate was 60.9% and significantly less in the emergency group (P = 0.026). The mean duration from surgery to recurrence, 3-year disease-free survival, and overall survival were 1.19, 2.81, and 3.11, respectively. Conclusion: Elective group was associated with better 3-year survival, longer overall, and 3-year disease-free survival compared to the emergency group. The disease recurrence rate was comparable in both groups, mainly in the first two years after curative resection.
MeSH term(s)	Humans ; Treatment Outcome ; Retrospective Studies ; Neoplasm Recurrence, Local ; Colonic Neoplasms/surgery ; Colonic Neoplasms/pathology ; Disease-Free Survival
Language	English
Publishing date	2023-04-04
Publishing country	India
Document type	Journal Article
ZDB-ID	2299174-8
ISSN	1998-4049 ; 1319-3767
ISSN (online)	1998-4049
ISSN	1319-3767
DOI	10.4103/sjg.sjg_31_23
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