Genetic polymorphisms in mediators of inflammation and gastric precancerous lesions

Canzian, Federico; Franceschi, Silvia; Plummer, Martyn; Doorn, Leen Jan Van; Lu, Yanhui; Gioia-Patricola, Lydie; Vivas, Jorge; López, Gladys; Severson, Richard K.; Schwartz, Ann G.; Muñóz, Núbia; Kato, Ikuko

doi:10.1097/cej.0b013e3282b6fd88

Cited by 14 publications

(14 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NOS2 polymorphisms have been studied in several types of diseases, including malaria [18-20,23], diabetes [34], rheumatoid arthritis [35], osteomyelitis [36] and asthma [33], where NO production has been implicated in the disease pathogenesis. However, the role of NOS2 promoter region variants -954G/C and -1173C/T and of the Ser 608 Leu substitution in exon 16 in gastric carcinogenesis is still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, Shen et al [17] found a significant association between this polymorphism and the risk of gastric cancer only in patients with a history of smoking habit or alcohol intake. On the other hand, Canzian et al [36] observed an association between the Ser 608 Leu polymorphism and atrophic gastritis, while Holla et al [33] found this polymorphism to be associated with susceptibility to asthma.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Gastric cancer is associated with NOS2-954G/C polymorphism and environmental factors in a Brazilian population

2010

View full text Add to dashboard Cite

BackgroundGastric cancer can progress from a chronic inflammation of the gastric mucosa resulting from Helicobacter pylori infection that activates the inflammatory response of the host. Therefore, polymorphisms in genes involved in the inflammatory response, such as inducible nitric oxide synthase (NOS2), have been implicated in gastric carcinogenesis. The aim of this study was to evaluate the association of NOS2 polymorphisms Ser608Leu (rs2297518) in exon 16, -954G/C and -1173C/T, both in the promoter region, with gastric cancer and chronic gastritis and the association of cancer with risk factors such as smoking, alcohol intake and H. pylori infection.MethodsWe conducted a population-based case-control study in 474 Southeast Brazilian individuals (150 with gastric cancer, 160 with chronic gastritis, and 164 healthy individuals), in which we performed NOS2 genotyping by PCR-RFLP.ResultsSNP Ser608Leu was not associated with risk of chronic gastritis or gastric cancer. The polymorphic allele -1173T was not found in the studied population. However, the frequency of -954GC+CC genotypes was significantly higher (p < 0.01) in the cancer group (48.7%) than in both the gastritis (28.1%) and the control (29.9%) groups. Multivariate logistic regression showed that the NOS2 SNP -954G/C was associated with higher risk of gastric cancer (OR = 1.87; 95% CI = 1.12-3.13). We also observed an association with risk factors such as smoking and alcohol intake in both the gastric cancer (OR = 2.68; 95% CI = 1.58-4.53; OR = 3.60; 95% CI = 2.05-6.32, respectively) and the chronic gastritis (OR = 1.93; 95% CI = 1.19-3.13; OR = 2.79; 95% CI = 1.55-5.02, respectively) groups. This is the first report of increased risk of gastric cancer in association with the -954G/C polymorphism. These findings show that several polymorphisms in the promoter region of the NOS2 gene may contribute to the susceptibility to gastric cancer.ConclusionsPolymorphism NOS2 -954 G/C, along with alcohol intake and tobacco smoking, is associated with gastric cancer. However, the NOS2 Ser608Leu polymorphism was not associated with gastric carcinogenesis. The NOS2 -1173C/T polymorphism was absent in the studied population.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Gastric cancer is associated with NOS2-954G/C polymorphism and environmental factors in a Brazilian population

2010

View full text Add to dashboard Cite

show abstract

“…One explanation could be ̔the field carcinogenesis' and the adjacent normal mucosae are not ̔real' normal cells and that ̔the field carcinogenesis' has altered gene expression and is committed to tumorigenesis (15). Indeed, gastric cancer development is usually involved in premalignant diseases, such as dysplasia or chronic gastritis and H. pylori infection is a single most important risk factor in developing gastric cancer (16,17). In this context, the adjacent normal tissue may not be really 'normal'.…”

Section: Discussionmentioning

confidence: 99%

Programmed cell death 2 protein induces gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis in a p53-dependent manner

et al. 2014

View full text Add to dashboard Cite

Abstract. Programmed cell death 2 (PDCD2) is a highly conserved nuclear protein, and aberrant PDCD2 expression alters cell apoptosis. The present study aimed to investigate PDCD2 expression in gastric cancer. Tissue specimens from 34 gastric cancer patients were collected for analysis of PDCD2 expression using immunohistochemistry, western blotting and qRT-PCR. Gastric cancer cell lines (a p53-mutated MKN28 line and a wild-type p53 MKN45 line) were used to assess the effects of PDCD2 overexpression. p53 -/-nude mice were used to investigate the effect of PDCD2 on ultraviolet B (UVB)-induced skin carcinogenesis. The data showed that PDCD2 expression was reduced in gastric cancer tissue specimens, and loss of PDCD2 expression was associated with the poor survival of patients. PDCD2 expression induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis. The antitumor effects of PDCD2 expression were dependent on p53 expression in gastric cancer cells. Moreover, PDCD2 expression inhibited activity of the ATM/Chk1/2/p53 signaling pathway. In addition, PDCD2 expression suppressed UVB-induced skin carcinogenesis in p53 +/+ nude mice, but not in p53 -/-mice. The data from the present study demonstrated that loss of PDCD2 expression could contribute to gastric cancer development and progression and that PDCD2-induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis are p53-dependent.

show abstract

“…These are involved in the risk of developing different diseases, but with contradictory results. For example, Shen et al (2004) have discovered a significant association between this polymorphism and the risk of gastric cancer only in the case of smokers and alcohol consumers [14], whereas Canzian et al (2008) have noticed an association between polymorphism and gastric atrophy [21].…”

Section: Discussionmentioning

confidence: 99%

The association between chronic pancreatitis and the iNOS-2087A>G polymorphism

Pădureanu

Siloşi

Forţofoiu

et al. 2017

Romanian Journal of Internal Medicine

View full text Add to dashboard Cite

Introduction. Chronic pancreatitis is morphologically characterized by ductal dysplasia, breeding grounds for the proliferation of the ductal cells, the degenerative changes in pancreatic acinar cells and fibrosis, and it is defined on the basis of the clinical, morphological and functional criteria.Aim. The aim of our study is to examine the existence of a possible correlation between the iNOS-2087A>G polymorphism and chronic pancreatitis by means of the genetic analysis.Material and method. We have conducted the study at the Gastroenterology Clinic and the Research Center of Gastroenterology and Hepatology of the University of Medicine and Pharmacy, Craiova, between March 2015 – September 2016. The study had a prospective character. Both for the 58 patients diagnosed with chronic pancreatitis and for the 132 patients in the witness group, the biological material was represented by blood, (around 2.5 – 5 milliliters of venous blood) let on EDTA and kept at 4°C up to the separation of the DNA molecule. All the patients were genotyped for the iNOS – 2087A>G polymorphism, by means of the Real Time PCR technique with TaqMan probes.Results. Analysing the prevalence of the iNOS genotypes within the study group and witness group, we have noticed that, statistically speaking, there are no significant differences between the two groups.Conclusion. As a conclusion, in the study lot we can sustain that the risk of developing chronic pancreatitis is not increased by the presence of the iNOS-2087A>G polymorphism.

show abstract

Genetic polymorphisms in mediators of inflammation and gastric precancerous lesions

Cited by 14 publications

References 28 publications

Gastric cancer is associated with NOS2-954G/C polymorphism and environmental factors in a Brazilian population

Gastric cancer is associated with NOS2-954G/C polymorphism and environmental factors in a Brazilian population

Programmed cell death 2 protein induces gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis in a p53-dependent manner

The association between chronic pancreatitis and the iNOS-2087A>G polymorphism

Contact Info

Product

Resources

About