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Tang G, Sun K, Ding G, Wu J. Low Expression of TSTD2 Serves as a Biomarker for Poor Prognosis in Kidney Renal Clear Cell Carcinoma. Int J Gen Med 2023; 16:1437-1453. [PMID: 37114071 PMCID: PMC10126726 DOI: 10.2147/ijgm.s408854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Accepted: 04/17/2023] [Indexed: 04/29/2023] Open
Abstract
Introduction Kidney renal clear cell carcinoma (KIRC) is a common cancer in people worldwide, and one of the main issues is developing suitable biomarkers. This study aims to investigate the expression of TSTD2 in KIRC and its impact on prognosis. Methods RNA sequencing data from TCGA and GTEx were gathered to examine the functional enrichment of TSTD2-related differentially expressed genes (DEGs) using GO/KEGG, GSEA, immunocyte permeation analysis, and protein-protein interaction (PPI) network analysis. The Kaplan‒Meier-Cox regression model and the prognostic nomograph model were used to assess the clinical importance of TSTD2 in KIRC. R software was used to analyze the included studies. Finally, verification of cells and tissues was performed using immunohistochemical staining and quantitative real‒time PCR. Results In contrast to normal samples, it was discovered that TSTD2 was underexpressed in a number of malignancies, including KIRC. Furthermore, in 163 KIRC samples, low expression of TSTD2 was linked to a poor prognosis, as were subgroups with age greater than 60, the integrin pathway, the development of elastic fibers, and high TNM stage, pathologic stage, and histologic grade (P < 0.05). Age and TNM stage were included in the nomogram prognostic model, and low TSTD2 was a prognostic predictor that could be used independently in Cox regression analysis. In addition, 408 DEGs with 111 upregulated genes and 297 downregulated genes were found between the high- and low-expression groups. Conclusion The diminished expression of TSTD2 may serve as a biomarker for unfavorable outcomes in KIRC, and holds potential as a target for therapeutic interventions.
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Affiliation(s)
- Gonglin Tang
- Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, People’s Republic of China
| | - Kai Sun
- Urology Department, Shandong Province Hospital, Shandong University, Jinan, 250021, People’s Republic of China
| | - Guixin Ding
- Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, People’s Republic of China
| | - Jitao Wu
- Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, People’s Republic of China
- Correspondence: Jitao Wu, Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, People’s Republic of China, Email
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Syam AF, Waskito LA, Rezkitha YAA, Simamora RM, Yusuf F, Danchi KE, Bakry AF, Arnelis, Mulya E, Siregar GA, Sugihartono T, Maulahela H, Doohan D, Miftahussurur M, Yamaoka Y. Helicobacter pylori in the Indonesian Malay's descendants might be imported from other ethnicities. Gut Pathog 2021; 13:36. [PMID: 34088343 PMCID: PMC8178862 DOI: 10.1186/s13099-021-00432-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 05/21/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Even though the incidence of H. pylori infection among Malays in the Malay Peninsula is low, we observed a high H. pylori prevalence in Sumatra, which is the main residence of Indonesian Malays. H. pylori prevalence among Indonesian Malay descendants was investigated. RESULTS Using a combination of five tests, 232 recruited participants were tested for H- pylori and participants were considered positive if at least one test positive. The results showed that the overall H. pylori prevalence was 17.2%. Participants were then categorized into Malay (Aceh, Malay, and Minang), Java (Javanese and Sundanese), Nias, and Bataknese groups. The prevalence of H. pylori was very low among the Malay group (2.8%) and no H. pylori was observed among the Aceh. Similarly, no H. pylori was observed among the Java group. However, the prevalence of H. pylori was high among the Bataknese (52.2%) and moderate among the Nias (6.1%). Multilocus sequence typing showed that H. pylori in Indonesian Malays classified as hpEastAsia with a subpopulation of hspMaori, suggesting that the isolated H. pylori were not a specific Malays H. pylori. CONCLUSIONS Even though the ethnic groups live together as a community, we observed an extremely low H. pylori infection rate among Indonesian Malay descendants with no specific Indonesian Malay H. pylori. The results suggest that H. pylori was not originally among these groups and H. pylori was imported from other ethnic groups.
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Affiliation(s)
- Ari Fahrial Syam
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine-Cipto Mangunkusumo Teaching Hospital, University of Indonesia, Jakarta, Indonesia
| | - Langgeng Agung Waskito
- Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
| | - Yudith Annisa Ayu Rezkitha
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
- Department of Internal Medicine, Faculty of Medicine, University of Muhammadiyah Surabaya, Surabaya, Indonesia
| | - Rentha Monica Simamora
- Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Fauzi Yusuf
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Dr. Zainoel Abidin General Hospital, Universitas Syiah Kuala, Banda Aceh, Indonesia
| | - Kanserina Esthera Danchi
- Department of Internal Medicine, Dr. M Thomsen Nias Gunungsitoli General Hospital, Nias, Indonesia
| | - Ahmad Fuad Bakry
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Sriwijaya University, Palembang, Indonesia
| | - Arnelis
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Andalas University, Padang, Indonesia
| | - Erwin Mulya
- Department of Internal Medicine, Cimacan General Hospital, Cianjur, Indonesia
| | - Gontar Alamsyah Siregar
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatera Utara, Medan, Indonesia
| | - Titong Sugihartono
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine-Dr Soetomo Teaching Hospital, Universitas Airlangga, Jalan Mayjend Prof. Dr. Moestopo No. 6-8, Surabaya, 60286, Indonesia
| | - Hasan Maulahela
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine-Cipto Mangunkusumo Teaching Hospital, University of Indonesia, Jakarta, Indonesia
| | - Dalla Doohan
- Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Muhammad Miftahussurur
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine-Dr Soetomo Teaching Hospital, Universitas Airlangga, Jalan Mayjend Prof. Dr. Moestopo No. 6-8, Surabaya, 60286, Indonesia.
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama Machi, Yufu City, Oita, 879-5593, Japan.
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX, USA.
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Hatta W, Tong D, Lee YY, Ichihara S, Uedo N, Gotoda T. Different time trend and management of esophagogastric junction adenocarcinoma in three Asian countries. Dig Endosc 2017; 29 Suppl 2:18-25. [PMID: 28425657 DOI: 10.1111/den.12808] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Accepted: 01/11/2017] [Indexed: 02/06/2023]
Abstract
Esophagogastric junction (EGJ) adenocarcinoma has been on the increase in Western countries. However, in Asian countries, data on the incidence of EGJ adenocarcinoma are evidently lacking. In the present review, we focus on the current clinical situation of EGJ adenocarcinoma in three Asian countries: Japan, Hong Kong, and Malaysia. The incidence of EGJ adenocarcinoma has been reported to be gradually increasing in Malaysia and Japan, whereas it has stabilized in Hong Kong. However, the number of cases in these countries is comparatively low compared with Western countries. A reason for the reported difference in the incidence and time trend of EGJ adenocarcinoma among the three countries may be explained by two distinct etiologies: one arising from chronic gastritis similar to distal gastric cancer, and the other related to gastroesophageal reflux disease similar to esophageal adenocarcinoma including Barrett's adenocarcinoma. This review also shows that there are several concerns in clinical practice for EGJ adenocarcinoma. In Hong Kong and Malaysia, many EGJ adenocarcinomas have been detected at a stage not amenable to endoscopic resection. In Japan, histological curability criteria for endoscopic resection cases have not been established. We suggest that an international collaborative study using the same definition of EGJ adenocarcinoma may be helpful not only for clarifying the characteristics of these cancers but also for improving the clinical outcome of these patients.
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Affiliation(s)
- Waku Hatta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Daniel Tong
- Division of Esophageal and Upper Gastrointestinal Surgery, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Yeong Yeh Lee
- Department of Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
| | - Shin Ichihara
- Department of Surgical Pathology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Noriya Uedo
- Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan
| | - Takuji Gotoda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
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Abadi ATB, Ierardi E, Lee YY. Why do we still have Helicobacter Pylori in our Stomachs. Malays J Med Sci 2015; 22:70-75. [PMID: 28239271 PMCID: PMC5295741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2015] [Accepted: 06/17/2015] [Indexed: 06/06/2023] Open
Abstract
The existence of any infectious agent in a highly acidic human stomach is contentious, but the chance finding of Helicobacter pylori is by no means an accident. Once H. pylori colonises the gastric mucosa, it can persist for a lifetime, and it is intriguing why our immune system is able to tolerate its existence. Some conditions favour the persistence of H. pylori in the stomach, but other conditions oppose the colonisation of this bacterium. Populations with high and extremely low prevalence of H. pylori provide useful insights on the clinical outcomes that are associated with this type of infection. Adverse clinical outcomes including peptic ulcer disease and gastric cancer depend on a delicate balance between a harmless inflammation and a more severe kind of inflammation. Is the only good H. pylori really a dead H. pylori? The jury is still out.
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Affiliation(s)
- Amin Talebi Bezmin Abadi
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-111, Tehran, Iran
| | - Enzo Ierardi
- Division of Gastroenterology, Department of Emergency and Organ Transplantation, Piazza Giulio Cesare, 70124 Bari, Italy
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia
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Jamaludin S, Mustaffa N, Che Hamzah NA, Syed Abdul Aziz SH, Lee YY. Diagnostic accuracy of reused Pronto Drytest and CLOtest in the detection of Helicobacter pylori infection. BMC Gastroenterol 2015; 15:101. [PMID: 26264957 PMCID: PMC4534069 DOI: 10.1186/s12876-015-0332-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Accepted: 08/04/2015] [Indexed: 12/17/2022] Open
Abstract
Background Unchanged substrate in a negative rapid urease test may be reused to detect Helicobacter pylori (H. pylori). This could potentially reduce costs and wastage in low prevalence and resource-poor settings. We thus aimed to investigate the diagnostic accuracy of reused Pronto Dry® and CLOtest® kits, comparing this to the use of new Pronto Dry® test kits and histopathological evaluation of gastric mucosal biopsies. Methods Using a cross-sectional study design, subjects who presented for upper endoscopy due to various non-emergent causes had gastric biopsies obtained at three adjacent sites. Biopsy samples were tested for H. pylori using a reused Pronto Dry® test, a reused CLOtest®, a new Pronto Dry® test and histopathological examination. Concordance rates, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were then determined. Results A total of 410 subjects were recruited. The sensitivity and diagnostic accuracy of reused Pronto Dry® tests were 72.60 % (95 % CI, 61.44 – 81.51) and 94.15 % (95 % CI, 91.44 – 96.04) respectively. For reused CLOtests®, the sensitivity and diagnostic accuracy were 93.15 % (95 % CI 85.95 – 97.04) and 98.29 % (95 % CI 96.52 – 99.17) respectively. There were more true positives for new and reused Pronto Dry® pallets as compared to new and reused CLOtests® when comparing colour change within 30 min vs. 31–60 min (P < 0.001 and P = 0.7 respectively). Conclusion Negative Pronto Dry® and CLOtest® kits may be reused in a low prevalence setting where cost issues remain paramount. Reused CLOtest® kits have better accuracy than reused Pronto Dry® tests. Reused Pronto Dry® tests however have a more rapid colour change whilst maintaining diagnostic accuracy.
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Affiliation(s)
- Shahidi Jamaludin
- School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
| | - Nazri Mustaffa
- School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
| | | | | | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
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Wan Juhari WK, Md Tamrin NA, Mat Daud MHR, Isa HW, Mohd Nasir N, Maran S, Abdul Rajab NS, Ahmad Amin Noordin KB, Nik Hassan NN, Tearle R, Razali R, Merican AF, Zilfalil BA. A whole genome analyses of genetic variants in two Kelantan Malay individuals. THE HUGO JOURNAL 2014; 8:4. [PMID: 27090252 PMCID: PMC4685156 DOI: 10.1186/s11568-014-0004-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/04/2014] [Accepted: 09/19/2014] [Indexed: 12/29/2022]
Abstract
Background The sequencing of two members of the Royal Kelantan Malay family genomes will provide insights on the Kelantan Malay whole genome sequences. The two Kelantan Malay genomes were analyzed for the SNP markers associated with thalassemia and Helicobacter pylori infection. Helicobacter pylori infection was reported to be low prevalence in the north-east as compared to the west coast of the Peninsular Malaysia and beta-thalassemia was known to be one of the most common inherited and genetic disorder in Malaysia. Result By combining SNP information from literatures, GWAS study and NCBI ClinVar, 18 unique SNPs were selected for further analysis. From these 18 SNPs, 10 SNPs came from previous study of Helicobacter pylori infection among Malay patients, 6 SNPs were from NCBI ClinVar and 2 SNPs from GWAS studies. The analysis reveals that both Royal Kelantan Malay genomes shared all the 10 SNPs identified by Maran (Single Nucleotide Polymorphims (SNPs) genotypic profiling of Malay patients with and without Helicobacter pylori infection in Kelantan, 2011) and one SNP from GWAS study. In addition, the analysis also reveals that both Royal Kelantan Malay genomes shared 3 SNP markers; HBG1 (rs1061234), HBB (rs1609812) and BCL11A (rs766432) where all three markers were associated with beta-thalassemia. Conclusions Our findings suggest that the Royal Kelantan Malays carry the SNPs which are associated with protection to Helicobacter pylori infection. In addition they also carry SNPs which are associated with beta-thalassemia. These findings are in line with the findings by other researchers who conducted studies on thalassemia and Helicobacter pylori infection in the non-royal Malay population.
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Affiliation(s)
- Wan Khairunnisa Wan Juhari
- Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia
| | - Nur Aida Md Tamrin
- Faculty of Resource Science and, Technology Universiti Malaysia Sarawak, Sarawak, Malaysia
| | | | - Hatin Wan Isa
- Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia, Universiti Sains Malaysia, Kelantan, Malaysia
| | - Nurfazreen Mohd Nasir
- Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia, Universiti Sains Malaysia, Kelantan, Malaysia
| | - Sathiya Maran
- Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia, Universiti Sains Malaysia, Kelantan, Malaysia
| | - Nur Shafawati Abdul Rajab
- Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia, Universiti Sains Malaysia, Kelantan, Malaysia
| | | | | | - Rick Tearle
- Complete Genomics Inc, 2071 Stierlin Court, Mountain View, 94043, CA, USA
| | | | - Amir Feisal Merican
- Centre of Research for Computational Sciences and Informatics in Biology, Bioindustry, Environment, Agriculture and Healthcare (CRYSTAL), Kuala Lumpur, Malaysia.,Institute of Biological Science, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Bin Alwi Zilfalil
- Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
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Talebi Bezmin Abadi A. Helicobacter pylori: A Beneficial Gastric Pathogen? Front Med (Lausanne) 2014; 1:26. [PMID: 25593901 PMCID: PMC4291894 DOI: 10.3389/fmed.2014.00026] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2014] [Accepted: 08/12/2014] [Indexed: 12/24/2022] Open
Affiliation(s)
- Amin Talebi Bezmin Abadi
- Department of Medical Microbiology, University Medical Center Utrecht , Utrecht , Netherlands ; Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University , Tehran , Iran
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Lee YY, Raj SM, Graham DY. Helicobacter pylori infection--a boon or a bane: lessons from studies in a low-prevalence population. Helicobacter 2013; 18:338-46. [PMID: 23607896 PMCID: PMC3974589 DOI: 10.1111/hel.12058] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Helicobacter pylori (H. pylori) infection is etiologically associated with gastric cancer and peptic ulcer diseases which are both important public health burdens which could be largely eliminated by H. pylori eradication. However, some investigators urge caution based on the hypothesis that eradication of H. pylori may result in an increase in the incidence of gastroesophageal reflux disease, esophageal adenocarcinoma, and childhood asthma. The ethnic Malays of northeastern Peninsular Malaysia have long had a low prevalence of H. pylori infection and, as expected, the incidence of gastric cancer and its precursor lesions is exceptionally low. The availability of a population with a low H. pylori prevalence and generally poor sanitation allows separation of H. pylori from the hygiene hypothesis and direct testing of whether absence of H. pylori is associated with untoward consequence. Contrary to predictions, in Malays, erosive esophagitis, Barrett's esophagus, distal esophageal cancers, and childhood asthma are all of low incidence. This suggests that H. pylori is not protective rather the presence of H. pylori infection is likely a surrogate for poor hygiene and not an important source of antigens involved in the hygiene hypothesis. Helicobacter pylori in Malays is related to transmission from H. pylori-infected non-Malay immigrants. The factors responsible for low H. pylori acquisition, transmission, and burden of H. pylori infection in Malays remain unclear and likely involves a combination of environmental, host (gene polymorphisms), and strain virulence factors. Based on evidence from this population, absence of H. pylori infection is more likely to be boon than a bane.
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Affiliation(s)
- Yeong Yeh Lee
- Department of Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | | | - David Y. Graham
- Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA
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Lee YY, Chua ASB. What indigestion means to the malays? J Neurogastroenterol Motil 2013; 19:295-300. [PMID: 23875095 PMCID: PMC3714406 DOI: 10.5056/jnm.2013.19.3.295] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2013] [Revised: 05/10/2013] [Accepted: 05/12/2013] [Indexed: 12/13/2022] Open
Abstract
Despite being a large ethnic group within the South-East Asia, there is a paucity of reported literatures on dyspepsia in the Malay population. Recent population-based studies indicate that uninvestigated dyspepsia, based on the Rome II criteria, is reported in 12.8% and 11.6% of Malays in the urban and rural communities respectively. Organic causes of dyspepsia including upper gastrointestinal tract cancers, its precancerous lesions, and erosive diseases are uncommon which is largely due to an exceptionally low prevalence of Helicobacter pylori infection in this population. On the other hand, functional dyspepsia and irritable bowel syndrome are relatively common in the Malays than expected. Within a primary care setting, functional dyspepsia, based on the Rome III criteria, is reported in 11.9% of Malays, of which epigastric pain syndrome is found to be more common. Married Malay females are more likely to have functional dyspepsia and psychosocial alarm symptoms. Also based on the Rome III criteria, irritable bowel syndrome, commonly overlapped with functional dyspepsia, is reported in 10.9% of Malays within a community-based setting. Rather than psychosocial symptoms, red flags are most likely to be reported among the Malays with irritable bowel syndrome despite having a low yield for organic diseases. Based upon the above observations, "proton pump inhibitor test" is probably preferable than the "test and treat H. pylori" strategy in the initial management of dyspepsia among the Malays.
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Affiliation(s)
- Yeong Yeh Lee
- Department of Medicine, School of Medical Sciences, University Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
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Maran S, Lee YY, Xu S, Rajab NS, Hasan N, Syed Abdul Aziz SH, Majid NA, Zilfalil BA. Gastric precancerous lesions are associated with gene variants in Helicobacter pylori-susceptible ethnic Malays. World J Gastroenterol 2013; 19:3615-3622. [PMID: 23801863 PMCID: PMC3691040 DOI: 10.3748/wjg.v19.i23.3615] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2013] [Revised: 03/22/2013] [Accepted: 04/10/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify genes associated with gastric precancerous lesions in Helicobacter pylori (H. pylori)-susceptible ethnic Malays.
METHODS: Twenty-three Malay subjects with H. pylori infection and gastric precancerous lesions identified during endoscopy were included as “cases”. Thirty-seven Malay subjects who were H. pylori negative and had no precancerous lesions were included as “controls”. Venous blood was collected for genotyping with Affymetrix 50K Xba1 kit. Genotypes with call rates < 90% for autosomal single nucleotide polymorphisms (SNPs) were excluded. For each precancerous lesion, associated SNPs were identified from Manhattan plots, and only SNPs with a χ2P value < 0.05 and Hardy Weinberg Equilibrium P value > 0.5 was considered as significant markers.
RESULTS: Of the 23 H. pylori-positive subjects recruited, one sample was excluded from further analysis due to a low genotyping call rate. Of the 22 H. pylori-positive samples, atrophic gastritis only was present in 50.0%, complete intestinal metaplasia was present in 18.25%, both incomplete intestinal metaplasia and dysplasia was present in 22.7%, and dysplasia only was present in 9.1%. SNPs rs9315542 (UFM1 gene), rs6878265 (THBS4 gene), rs1042194 (CYP2C19 gene) and rs10505799 (MGST1 gene) were significantly associated with atrophic gastritis, complete intestinal metaplasia, incomplete metaplasia with foci of dysplasia and dysplasia, respectively. Allele frequencies in “cases”vs“controls” for rs9315542, rs6878265, rs1042194 and rs10505799 were 0.4 vs 0.06, 0.6 vs 0.01, 0.6 vs 0.01 and 0.5 vs 0.02, respectively.
CONCLUSION: Genetic variants possibly related to gastric precancerous lesions in ethnic Malays susceptible to H. pylori infection were identified for testing in subsequent trials.
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