scholarly journals Novel Risk Associations between microRNA Polymorphisms and Gastric Cancer in a Chilean Population

2021 ◽  
Vol 23 (1) ◽  
pp. 467
Author(s):  
Natalia Landeros ◽  
Alejandro H. Corvalan ◽  
Maher Musleh ◽  
Luis A. Quiñones ◽  
Nelson M. Varela ◽  
...  

Gastric cancer (GC) is the fifth leading cause of cancer deaths in the world, with variations across geographical regions and ethnicities. Emerging evidence indicates that miRNA expression is dysregulated in GC and its polymorphisms may contribute to these variations, which has yet to be explored in Latin American populations. In a case-control study of 310 GC patients and 311 healthy donors from Chile, we assessed the association of 279 polymorphisms in 242 miRNA genes. Two novel polymorphisms were found to be associated with GC: rs4822739:C>G (miR-548j) and rs701213:T>C (miR-4427). Additionally, rs1553867776:T>TCCCCA (miR-4274) and rs12416605:C>T (miR-938) were associated with intestinal-type GC, and rs4822739:C>G (miR-548j) and rs1439619:T>G (miR-3175) with TNM I-II stage. The polymorphisms rs6149511:T> TGAAGGGCTCCA (miR-6891), rs404337:G>A (miR-8084), and rs1439619:T>G (miR-3175) were identified among H.pylori-infected GC patients and rs7500280:T>C (miR-4719) and rs1439619:T>G (miR-3175) were found among H. pylori cagPAI+ infected GC cases. Prediction analysis suggests that seven polymorphisms could alter the secondary structure of the miRNA, and the other one is located in the seed region of miR-938. Targets of miRNAs are enriched in GC pathways, suggesting a possible biological effect. In this study, we identified seven novel associations and replicated one previously described in Caucasian population. These findings contribute to the understanding of miRNA genetic polymorphisms in the GC pathogenesis.

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Zhijing Xue ◽  
Yuanhai You ◽  
Lihua He ◽  
Yanan Gong ◽  
Lu Sun ◽  
...  

Abstract Background The cytotoxin-associated gene A (cagA) is one of the most important virulence factors of Helicobacter pylori (H. pylori). There is a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal of CagA protein. This repeat region is thought to play an important role in the pathogenesis of gastrointestinal diseases. The aim of this study was to investigate the diversity of cagA 3′ variable region and the amino acid polymorphisms in the EPIYA segments of the CagA C-terminal region of H. pylori, and their association with gastroduodenal diseases. Methods A total of 515 H. pylori strains from patients in 14 different geographical regions of China were collected. The genomic DNA from each strain was extracted and the cagA 3′ variable region was amplified by polymerase chain reaction (PCR). The PCR products were sequenced and analyzed using MEGA 7.0 software. Results A total of 503 (97.7%) H. pylori strains were cagA-positive and 1,587 EPIYA motifs were identified, including 12 types of EPIYA or EPIYA-like sequences. In addition to the four reported major segments, several rare segments (e.g., B′, B″ and D′) were defined and 20 different sequence types (e.g., ABD, ABC) were found in our study. A total of 481 (95.6%) strains carried the East Asian type CagA, and the ABD subtypes were most prevalent (82.1%). Only 22 strains carried the Western type CagA, which included AC, ABC, ABCC and ABCCCC subtypes. The CagA-ABD subtype had statistical difference in different geographical regions (P = 0.006). There were seven amino acid polymorphisms in the sequences surrounding the EPIYA motifs, among which amino acids 893 and 894 had a statistical difference with gastric cancer (P = 0.004). Conclusions In this study, 503 CagA sequences were studied and analyzed in depth. In Chinese population, most H. pylori strains were of the CagA-ABD subtype and its presence was associated with gastroduodenal diseases. Amino acid polymorphisms at residues 893 and 894 flanking the EPIYA motifs had a statistically significant association with gastric cancer.


2007 ◽  
Vol 102 (1) ◽  
pp. 40-45 ◽  
Author(s):  
Khean-Lee Goh ◽  
Phaik-Leng Cheah ◽  
Noorfaridah Md ◽  
Kia-Fatt Quek ◽  
Navaratnam Parasakthi

2021 ◽  
Author(s):  
Zhijing Xue ◽  
Yuanhai You ◽  
Lihua He ◽  
Yanan Gong ◽  
Lu Sun ◽  
...  

Abstract Background: The cytotoxin-associated gene A (cagA) is one of the most important virulence factors of Helicobacter pylori (H. pylori). There is a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal of CagA protein. This repeat region is thought to play an important role in the pathogenesis of gastrointestinal diseases. The aim of this study was to investigate the diversity of cagA 3’ variable region and the amino acid polymorphisms in the EPIYA segments of the CagA C-terminal region of H. pylori, and their association with gastroduodenal diseases.Methods: A total of 515 H. pylori strains from patients in 14 different geographical regions of China were collected. The genomic DNA from each strain was extracted and the cagA 3’ variable region was amplified by polymerase chain reaction (PCR). The PCR products were sequenced and analyzed using MEGA 7.0 software.Results: A total of 503 (97.7%) H. pylori strains were cagA-positive and 1,587 EPIYA motifs were identified, including 12 types of EPIYA or EPIYA-like sequences. In addition to the four reported major segments, several rare segments (e.g., B’, B’’ and D’) were defined and 20 different sequence types (e.g., ABD, ABC) were found in our study. A total of 481 (95.6%) strains carried the East Asian type CagA, and the ABD subtypes were most prevalent (82.1%). Only 22 strains carried the Western type CagA, which include AC, ABC, ABCC and ABCCCC subtypes. The CagA-ABD subtype had statistical difference in different geographic regions (P = 0.006). There are seven amino acid polymorphisms in the sequences surrounding the EPIYA motifs, among which amino acid residue 893 and 894 had a statistical difference with gastric cancer (P = 0.004).Conclusions: In this study, 503 CagA sequences was studied and analyzed in depth. In Chinese population, most H. pylori strains are of the CagA-ABD subtype and its presence was associated with gastroduodenal diseases. Amino acid polymorphisms at residue 893 and 894 flanking the EPIYA motif had a statistically significant association with gastric cancer.


2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Yifeng Zhang ◽  
Jin Yan ◽  
Chao Li ◽  
Xiaoyong Wang ◽  
Yu Dong ◽  
...  

Abstract Background The aim of this study was to investigate the role of long non-coding RNA (lncRNA) H19 in gastric cancer (GC) with Helicobacter pylori (H. pylori). Methods H19 expression in peripheral blood from H. pylori+/− GC patients and healthy donors (control) as well as in GC tissues and cells were detected by qRT-PCR. Cell proliferation was evaluated by CCK-8 assay. Cell migration and invasion were evaluated by Transwell assay. The levels of pro-inflammatory cytokines were determined by ELISA. The protein levels of IκBα, p-IκBα and p65 were determined by western blotting. Results H19 expression was upregulated in H. pylori-infected GC tissues and cells. Furthermore, H. pylori promoted GC cell viability, migration, invasion and inflammatory response. Moreover, H19 overexpression promoted the proliferation, migration and invasion of H. pylori-infected GC cells via enhancing NF-κB-induced inflammation. Conclusions LncRNA H19 promotes H. pylori-induced GC cell growth via enhancing NF-κB-induced inflammation.


2020 ◽  
Author(s):  
zhijing Xue ◽  
Yuanhai You ◽  
Lihua He ◽  
Yanan Gong ◽  
Lu Sun ◽  
...  

Abstract Background: CagA is one of the most important virulence factors of Helicobacter pylori (H. pylori). There is a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the CagA 3’ variable region. This repeat region is thought to play an important role in the pathogenesis of gastrointestinal diseases. The aim of this study was to investigate the diversity of CagA 3’ variable region and the amino acid polymorphisms in the EPIYA segments, and their association with gastroduodenal diseases.Methods: A total of 515 H. pylori isolates from patients in 14 different geographical regions of China were collected and the genomic DNA was extracted. The 3’ variable region of the cagA was amplified by polymerase chain reaction (PCR) and then followed by DNA sequencing, and the amino acid sequences were analyzed with MEGA 7.0 software.Results: A total of 503 (97.7%) H. pylori isolates were cagA-positive and 1,587 EPIYA motifs were obtained, including 12 types of EPIYA or EPIYA-like sequences. In addition to the four reported major segments, several rare segments (e.g., B’, B’’ and D’) were defined and 20 different sequence types (e.g., ABD, ABC) were found in our study. A total of 481 (95.6%) strains were East Asian type, most of them were ABD subtype (82.1%). Only 22 strains were Western type, including types AC, ABC, ABCC and ABCCCC. The CagA-ABD subtype had statistical difference in different geographic regions (P=0.006). There are seven amino acid polymorphisms in the sequences surrounding the EPIYA motifs, among which amino acid residue 893 and 894 had a statistical difference with gastric cancer (P=0.004).Conclusions: In this study, 503 CagA sequences was studied and analyzed in depth. In Chinese population, most H. pylori isolates are of the CagA-ABD subtype and its presence was associated with gastroduodenal disease. Amino acid polymorphisms at residue 893 and 894 flanking the EPIYA motif had a statistically significant association with gastric cancer.


Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Trang Hoa Nguyen ◽  
Trang Thi My Ho ◽  
Thien-Phuc Nguyen-Hoang ◽  
Shamsul Qumar ◽  
Thuc Tran Dang Pham ◽  
...  

Abstract Background The burden of Helicobacter pylori-induced gastric cancer varies based on predominant H. pylori population in various geographical regions. Vietnam is a high H. pylori burden country with the highest age-standardized incidence rate of gastric cancer (16.3 cases/100,000 for both sexes) in Southeast Asia, despite this data on the H. pylori population is scanty. We examined the global context of the endemic H. pylori population in Vietnam and present a contextual and comparative genomics analysis of 83 H. pylori isolates from patients in Vietnam. Results There are at least two major H. pylori populations are circulating in symptomatic Vietnamese patients. The majority of the isolates (~ 80%, 66/83) belong to the hspEastAsia and the remaining belong to hpEurope population (~ 20%, 17/83). In total, 66 isolates (66/83) were cagA positive, 64 were hspEastAsia isolates and two were hpEurope isolates. Examination of the second repeat region revealed that most of the cagA genes were ABD type (63/66; 61 were hspEastAsia isolates and two were hpEurope isolates). The remaining three isolates (all from hspEastAsia isolates) were ABC or ABCC types. We also detected that 4.5% (3/66) cagA gene from hspEastAsia isolates contained EPIYA-like sequences, ESIYA at EPIYA-B segments. Analysis of the vacA allelic type revealed 98.8% (82/83) and 41% (34/83) of the strains harboured the s1 and m1 allelic variant, respectively; 34/83 carried both s1m1 alleles. The most frequent genotypes among the cagA positive isolates were vacA s1m1/cagA + and vacA s1m2/cagA + , accounting for 51.5% (34/66) and 48.5% (32/66) of the isolates, respectively. Conclusions There are two predominant lineages of H. pylori circulating in Vietnam; most of the isolates belong to the hspEastAsia population. The hpEurope population is further divided into two smaller clusters.


2020 ◽  
Author(s):  
Jimi Kim ◽  
Hyejin Kim ◽  
Jeonghee Lee ◽  
Il Ju Choi ◽  
Young-Il Kim ◽  
...  

Abstract Background Chronic gastritis along with Helicobacter pylori (H. pylori) infection has been implicated in inflammatory response-related genes linked to the causation of gastric cancer (GC). Glutathione S-transferase Pi (GSTP1) plays a role in regulating oxidative stress and detoxification against carcinogenesis. In this study, we aimed to determine whether an antioxidant-rich diet was associated with GC risk and to identify how the association could be altered by GSTP1 genetic variants. Methods The study was conducted with 1,245 participants (415 cases and 830 controls) matched for age and sex. Dietary antioxidant capacity was estimated based on oxygen radical absorbance capacity (ORAC) incorporated with a semiquantitative food frequency questionnaire. Five single nucleotide polymorphisms (SNPs) of GSTP1 (rs1695, rs749174, rs1871042, rs4891, and rs947895) were selected among the exome array genotype data. Results High dietary ORAC showed inverse associations with GC (hydrophilic ORAC OR T3 vs. T1, 95% CI = 0.57, 0.39–0.82, P = 0.004; lipophilic ORAC = 0.66, 0.45–0.95, P = 0.021; total phenolics = 0.57, 0.39–0.83, P = 0.005). The polymorphism of rs1871042 increased GC risk (OR, 95% CI = 1.55, 1.10–2.16, P = 0.01, CT + TT vs. CC). A remarkably reduced risk of GC was observed among those who had a high dietary ORAC according to rs1871042 polymorphism (hydrophilic ORAC OR T3 vs. T1, 95% CI = 0.36, 0.17–0.78, P for trend = 0.013; lipophilic ORAC = 0.58, 0.37–0.93, P for trend = 0.021; total phenolics = 0.38, 0.17–0.83, P for trend = 0.019). Conclusions Our findings indicate that the association between dietary ORAC intake and GSTP1 polymorphisms as they pertain to the risk of GC may present new intervention strategies for GC patients.


Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 648 ◽  
Author(s):  
Valli De Re ◽  
Ombretta Repetto ◽  
Mariangela De Zorzi ◽  
Mariateresa Casarotto ◽  
Massimo Tedeschi ◽  
...  

Autoimmune atrophic gastritis (AAG) is associated with an increased risk of certain types of gastric cancer (GC). Helicobacter pylori (H. pylori) infection may have a role in the induction and/or maintenance of AAG and GC. Toll-like receptors (TLR) are essential for H. pylori recognition and subsequent innate and adaptive immunity responses. This study therefore aimed to characterize TLR polymorphisms, and features of bacterial flagellin A in samples from patients with AAG (n = 67), GC (n = 114) and healthy donors (HD; n = 97). TLR5 rs5744174 C/C genotype was associated with GC, lower IgG anti H. pylori response and a higher H. pylori flagellin A abundance and motility. In a subset of patients with AAG, H. pylori strains showed a reduction of the flagellin A abundance and a moderate motility compared with strains from GC patients, a prerequisite for active colonization of the deeper layers of the mucosa, host immune response and inflammation. TLR9 rs5743836 T allele showed an association with serum gastrin G17. In conclusion, our study suggests that alterations of flaA protein, moderate motility in H. pylori and two polymorphisms in TLR5 and TLR9 may favor the onset of AAG and GC, at least in a subset of patients. These findings corroborate the function of pathogen–host cell interactions and responses, likely influencing the pathogenetic process.


2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Amin Talebi Bezmin Abadi ◽  
Ashraf Mohabbati Mobarez

Helicobacter pyloriplays an important role in the pathogenesis of chronic gastritis, peptic ulceration, and noncardia gastric cancer. Several putative virulence factors forH. pylorihave been identified includingvacA,babA, andiceA. HopQ is one of the outer membrane proteins involved in bacterial adherence to gastric mucosa and has been suggested to also play a role in the virulence ofH. pylori. Due to the substantial geographic differences in the prevalence ofH. pylorivirulence factors reported, the main purpose of the current study was to investigate the association between differentH. pylorivirulencehopQalleles (types I and II) and patients with gastroduodenal disorders. The presence ofH. pyloriandhopQalleles in gastric biopsy specimens was identified by specific PCR assays.H. pyloritype IIhopQwas found to be significantly associated with gastric cancer patients (odds ratio: 3.47, 95% CI: 1.56–5.89). Information about the prevalence ofH. pylori hopQtype II can be used for determining the high-risk diseases type which is actually colonized byH. pylori hopQtype II positive strains. The presence ofH. pylori hopQtype II should be investigated in different geographical regions as confirmatory findings may provide a definite biomarker attributed to the pathogenesis of certain severe digestive diseases.


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