Fishing for ETV6/RUNX1 fusion and MLL gene rearrangements and their additional abnormalities in childhood acute lymphoblastic leukemia patients of Kashmir.

OBJECTIVE: Evidence suggests that ETV6/RUNX1 translocation in pediatric acute lymphocytic leukemia shows geographical variation. Therefore, the present study aimed at unveiling the incidence of ETV6/RUNX1 fusion in pediatric acute lymphocytic leukemia cases of this region using fluorescent in-situ hybridization. Besides, we aimed to determine the incidence of MLL gene rearrangement and the pattern of chromosomal abnormalities in this study group. METHODS: Samples from 57 acute lymphocytic leukemia cases of pediatric age group were subjected to fluorescent in-situ hybridization and conventional cytogenetic analysis using standard methods. RESULTS: Conventional cytogenetic analysis revealed chromosomal abnormalities in 19.3% cases. The other major chromosomal abnormalities reported were monosomies in 10.5%, hypodiploidy in 7%, marker chromosomes in 3.5% and deletions in 3.5% cases. We found a 44,XX,-7,-18, r(5), i(17q) complex karyotype in one of the cases. Fluorescent in-situ hybridization analysis revealed ETV6/RUNX1 translocation to be present in 28.07% cases and MLL gene rearrangement in 3.5% cases. 12.5% of ETV6/RUNX1 fusion positive cases were found to have a loss of ETV6 allele. Besides, 8.8% cases were found to exhibit a signal pattern suggestive of RUNX1 amplification. ETV6 gene deletion and MLL gene amplification was detected in 3.5% cases each, of our study. CONCLUSIONS: Frequency of ETV6/RUNX1 fusion oncogene was found to be higher in pediatric ALL cases of Kashmir region as compared to that reported from other parts of India. Besides, a case was found to have a karyotype viz 44,XX,-7,-18, r(5), i(17q) that has not been reported elsewhere in the childhood ALL.

Association of Vascular Endothelial Growth Factor 936 C/T Gene Polymorphism with Renal Allograft Outcome: A Study from North India.

The significance of vascular endothelial growth factor (VEGF) and its polymorphisms in renal allograft rejection has recently become the subject of extensive research. Recently, some studies have shown some role of VEGF in rejection episodes and graft survival. VEGF +936 C>T polymorphism is significant in the transcription regulation of VEGF. Herein, we report the results of a prospective, single-center study seeking an association of VEGF +936 C/T gene polymorphism and allograft rejection. One hundred and forty-seven kidney transplant recipients with age-and sex-matched controls were included in this study. VEGF 936 C/T genes were studied using restriction fragment length polymorphism analysis of the blood specimen of these patients. All patients were studied for allograft rejection, response to treatment, and overall graft survival. We found that CT genotype and T allele carrier state were associated with good graft outcomes (P = 0.008 and 0.002, respectively). There was a lower number of rejection episodes with T allele, although it was not a significant finding (P = 0.880). Our findings suggest that good graft outcome in kidney transplant recipients is associated with an increased frequency of the VEGF 936 CT genotype and T allele, and that determination of the T allele might be helpful for the identification of recipients with overall good graft survival.

Atopy in Kashmir-validation from a case control study with respect to IgE and Interleukin genes.

OBJECTIVES: Increased levels of serum Immunoglobulin-E (IgE) and different genetic variants of cytokines are common biochemical manifestation in Allergy. The current study was aimed to study the association of IgE and different variants of Interleukin-4 (IL-4), and Interleukin-13 (IL-13) genes with different kind of allergies. METHODS: A pre-tested questionnaire was used to collect all the dietary, life style and clinical details by a trained staff. A blood sample of 2 ml each was collected in coagulated and anti-coagulated vials. DNA and serum samples were extracted and stored until further use. Serum IgE were estimated by ELISA while as the genotypic analysis was done by PCR-RFLP methods. RESULTS: Statistically a significant difference of serum IgE levels were observed among cases and controls (P < 0.05). The observed significant difference of serum IgE levels were retained among subjects who also harboured variant genotypes of IL-4 and IL-13 genes (P < 0.05). Additionally, the above genetic variants significantly modified the risk of allergy when stratification was done based on various clinical characteristics. CONCLUSION: Our study suggests that increased IgE levels and in association with variant forms of IL-4 and IL-13 genes are significantly associated with different types of allergies in study population.

Galectin-1 as a predictive biomarker in ovarian cancer.

AIM: There is an urgent need to set up a useful biomarker for ovarian cancer. Galectin-1 is a promising carbohydrate-binding protein which plays a remarkable role in various malignancies yet its clinical significance is questionable. In this study, we have tested the clinical implications of serum Galectin-1 levels in patients with ovarian tumours. MAIN METHODS: Serum Galectin-1 levels were quantified in 84 newly diagnosed ovarian tumour patients and 20 healthy controls by Enzyme Linked Immuno Sorbent Assay during the course of the disease. Therefore the samples were taken at diagnosis, after surgery and after chemotherapy. KEY FINDINGS: The Galectin-1 levels were found to be associated with various variables of Ovarian Cancer patients. The levels were found to be prominently high in postmenopausal patients. Galectin-1 levels were raised in epithelial ovarian tumours with significantly high levels in serous subtype. A decrease in Galectin-1 levels post-surgical intervention and after receiving chemotherapy was found. Galectin-1 levels evidently distinguished between normal, benign, malignant and metastatic cases as compared to CA125 levels. Galectin-1 demonstrated to be a better biomarker than CA125 according to the Receiver Operating Characteristic (ROC) curve analysis. SIGNIFICANCE: The study emphasizes that serum Galectin-1 may serve as a better surrogate biomarker in Ovarian Cancer for early detection, discriminating between malignant and benign abdominal masses and monitoring the progression of the disease and response to treatment.

Promoter methylation and Ile105val polymorphism of GSTP1 gene in the modulation of colorectal cancer risk in ethnic Kashmiri population.

BACKGROUND: Glutathione-S-transferases (GSTs) are the most important phase II enzymes of the xenobiotic pathway responsible for the detoxification of carcinogens. GSTP1 gene polymorphisms are mostly associated with a lack or an alteration of enzymatic activity toward several substrates thus resulting in increased cancer susceptibility. GSTP1 promoter methylation is also frequently associated with tumor development or poor prognosis in a wide range of tumors. AIM: In this study, we examined the role of genetic polymorphism and promoter methylation of GSTP1 gene in the context of modulation of risk of colorectal cancer (CRC) in Kashmiri population. METHODS: This study used tissue tumor samples (114) and blood samples from (160) patients with CRC and 200 blood samples from healthy donors. GSTP1 polymorphism was studied using polymerase chain reaction (PCR)-restriction fragment length polymorphism and methylation using methylation-specific PCR. RESULTS: There was no significant association between GSTP1 I105V genotypes and the CRC (P>0.05). However, we found a significant association of the Val/Val variant genotype with the dwelling and smoking status (P-value < 0.05). Overall, the homozygous variant Val/Val genotype was associated with a modestly elevated risk for CRC (OR = 1.57; 95% CI = 0.67-3.57). Methyl-specific-PCR analysis revealed 25.4% methylation of the GSTP1 promoter in CRC cases and was not found to be statistically significantly associated with clinicopathological parameters of the CRC cases (P>0.05). Also, no significant associations of any of the three genotypes with promoter hypermethylation were observed. CONCLUSION: We conclude that promoter hypermethylation in homozygous GSTP1 mutants did not elevate the risk of CRC in Kashmiri population.

Real-time quantitative PCR: a reliable molecular diagnostic and follow-up tool for 'minimal residual disease' assessment in chronic myeloid leukemia.

Molecular monitoring of BCR-ABL transcript levels by real-time quantitative PCR is increasingly being used to diagnose the disease and assess treatment response in patients with chronic myeloid leukemia (CML). This has become particularly relevant when residual levels of leukemia usually fall below the level of detection by cytogenetic analysis. Forty-two CML patients, including 18 males (42.86%) and 24 females (57.14%) aged 7-75 years, were enlisted for the study and followed-up for the response to imatinib treatment. Patients were subjected to Multiplex RT-PCR (reverse-transcriptase PCR) and were all found to harbor either e13a2 or the e14a2, which could be analyzed by a single Taqman probe based quantitation kit (Geno-Sen's) to quantitate the BCR-ABL transcript load. The Multiplex RT-PCR and peripheral blood cytogenetics providing specific and sensitive detection of BCR-ABL fusion transcripts and metaphase signal load respectively were used as parallel reference tools to authenticate the q-PCR findings. There was 100% concordance between the multiplex RT-PCR and the q-PCR as every positive RT-PCR assay for a transcript reflected as q-PCR load of above 0% for that transcript. q-PCR also demonstrated a strong Pearson correlation with the cytogenetic response.

Prognostic Implication of BCR-ABL Fusion Transcript Variants in Chronic Myeloid Leukemia (CML) Treated with Imatinib. A First of Its Kind Study on CML Patients of Kashmir

Background: The prognostic significance of the common BCR-ABL transcripts like e13a2 (b2a2) and e14a2 (b3a2) in Chronic myeloid leukemia (CML) has been reported from patients treated with different tyrosine kinase inhibitors but its impact on clinical response and overall survival remains still unexplored. The aim of this study was to evaluate the prognostic significance of different transcript types in a cohort of CML patients treated with imatinib. Methods: A total 42 confirmed cases of Chronic Myeloid Leukemia (CML) patients were recruited into our cohort study and a multiplex Reverse Transcriptase-Polymerase Chain Reaction technique (RT-PCR) was used to detect 3 main transcript types 'e1a2', 'e13a2', and 'e14a2' found in CML. Results: Only two types of transcripts e13a2 (b2a2) and e14a2 (b3a2) were detected in our CML patients and none had the e1a2 type. All the patients were RT-PCR positive for either e13a2 or e14a2 fusion transcript demonstrating 100% concordance with their Ph+ve cytogenetic status at baseline. TLC count (range of 201-600x103/µl) and platelet count (range of 201-900x103/µl) at baseline were found to be associated more with the e14a2 (b3a2) than the e13a2 (b2a2) transcript type (p-value: 0.001). The two transcripts found did not relate significantly towards sex, age-group or indicated spleen size ranges as well as percentage ranges of blast cells. Conclusion: We conclude that there is no overall prognostic implication of either the e13a2 or the e14a2 transcript type across the spectrum of indicated clinical parameters evaluated. Even the overall survival analysis of the two transcript types revealed no prognostic association whatsoever.

Upregulation of vascular endothelial growth factor (VEGF), its role in progression and prognosis of non-small cell lung carcinoma.

Elevated VEGF mRNA (-ΔCT) was significantly associated with adenocarcinoma histology (vs squamous) and advanced NSCLC clinical stages in a univariable analysis; however, this association did not remain significant in the multivariable analysis. Of interest, a Kaplan-Meier analysis showed that NSCLC patients with higher VEGF mRNA (-ΔCT ≥10) had a significantly poorer overall survival and shorter postoperative relapse time in adenocarcinoma and in stage III/IV than those with VEGF mRNA of -ΔCT <10 (P < 0.001). The multivariable analysis confirmed that patients with higher VEGF mRNA levels, as well as with adenocarcinoma and advanced stages, were independent predictors of a poorer survival. However, only the histology of adenocarcinoma remained a significant prognostic factor of a shorter postoperative relapse in the multivariable model. Quantity of VEGF mRNA can be used as a prognosis factor to predict shorter overall survival in patients with NSCLC.

SNP and Haplotype Analysis of Vascular Endothelial Growth Factor (VEGF) Gene in Lung Cancer Patients of Kashmir

Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving tumor growth and metastasis. In this large case-control study, we investigated whether functional polymorphisms (+405C>G, +936C>T) in the VEGF gene are associated with the risk of lung cancer. The study investigates the association between variants of VEGF gene and lung cancer. We performed single nucleotide polymorphism (SNP), haplotype and linkage disequilibrium studies on 100 patients and 128 healthy controls with 2 SNPs in the VEGF gene. The results were analyzed using logistic regression models, adjusted for age and sex. No Significant association was detected between individual SNPs and lung cancer using all the models of inheritance (codominant, dominant, recessive, over dominant and additive) for finding an association between genotypes and the cancer risk. The P values obtained for two markers were nonsignificant (P>0.05). Haplotype analysis produced additional support for the non-association of individual haplotypes/ all haplotypes with the cancer risk (Global association P=0.56). Our findings suggest the non-involvement of genetic variants (+405C>G, +936C>T) of the VEGF gene in the etiology of lung cancer.

Single nucleotide polymorphisms, haplotype association and tumour expression of the vascular endothelial growth factor (VEGF) gene with lung carcinoma.

VEGF contains several polymorphic sites known to influence its expression. We examined the possible association between+405(-634)C>G,+936C>T,-2578C>A and lung cancer in 199 Kashmiri patients and 401 healthy controls. VEGF+405CG,+936CT+TT and-2578CA genotypes were significantly associated with lung cancer risk compared to VEGF+405CC,+936CC and-2578AA+CC genotypes [OR=0.07 (0.04-0.13), P<0.0001, OR=0.36 (0.25-0.52), P<0.0001 and 0.08 (0.05-0.13), P<0.0001]. Haplotype analysis revealed that CGA and TGA haplotypes of VEGF gene conveys the risk for lung cancer [OR=0.18 (0.10-0.33), P<0.0001 and 0.07 (0.03-0.13), P<0.0001]. VEGF expression revealed non-significant association with the genotypes of the three SNPs. In conclusion, the SNPs examined appear to influence lung cancer susceptibility while as genotypes of the SNPs don't appear to have significant association with VEGF mRNA expression in lung tumours.

The association between TNFα gene polymorphisms and susceptibility to rheumatoid arthritis in an ethnic Kashmiri population: relationship with disease activity and severity markers.

AIM: The aim of our study was to determine the genetic associations between polymorphisms of the TNFα gene (-308G/A and -238G/A) with disease susceptibility and severity in patients with rheumatoid arthritis (RA) in an ethnic Kashmiri population. METHODS: Allele and genotype frequencies of TNFα-308G/A and TNFα-238G/A polymorphisms were compared between 150 RA patients and 200 healthy controls by using polymerase chain reaction - restriction fragment length polymorphism method. Demographic, clinical and serological data were prospectively evaluated. Disease activity score (DAS28) was also assessed. RESULTS: We did not find any significant association between TNFα-308G/A and TNFα-238G/A polymorphism and RA risk (P > 0.05), but TNFα-308GG genotype was associated significantly with rheumatoid factor seropositivity (P < 0.01) and TNFα-238GA genotype was associated with swollen joint count < 5 (P = 0.04) as well as with less severe disease activity as measured by DAS28 score (P = 0.02). CONCLUSION: Our findings suggest the possible roles of TNFα-308GG and TNFα-238GA as important determinants for the development of certain manifestations and disease severity in RA in ethnic Kashmiri population.

Polymorphism of the DNA Repair Gene XRCC1 (Arg194Trp) and its role in Colorectal Cancer in Kashmiri Population: a Case Control Study.

BACKGROUND: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. MATERIALS AND METHODS: In this study we focused on the Arg194Trp polymorphism of the DNA repair gene XRCC1, involved in base excision repair (BER) and its role in colorectal cancer in Kashmiri population. A case-control study was conducted including 100 cases of colorectal cancer, and 100 hospital-based age- and sex-matched healthy controls to examine the role of XRCC1 genetic polymorphisms in the context of colorectal cancer risk for the Kashmiri population. RESULTS: Genotype analysis of XRCC1 Arg194Trp was conducted with a restriction fragment length polymorphism (RFLP) method. The overall association between the XRCC1 polymorphism and the CRC cases was found to be significant (p<0.05) with both the heterozygous genotype (Arg/Trp) as well as homozygous variant genotype (Trp/Trp) being moderately associated with the elevated risk for CRC [OR=2.01 (95% CI=1.03-3.94) and OR=5.2(95% CI=1.42-19.5)] respectively. CONCLUSIONS: Our results suggest an increased risk for CRC in individuals with XRCC1 Arg194Trp polymorphism suggesting BER repair pathway modulates the risk of developing colorectal cancer in the Kashmiri population.

Significant impact of IL-6 -174G/C but inverse relation with -634 C/G polymorphism in patients with non-small cell lung cancer in Kashmiri population.

To study the possible role of proinflammatory interleukin 6 -174 G>C (rs 1800795) and -634 C>G (rs 1800796) polymorphism in the pathogenesis of non-small cell lung cancer (NSCLC). A total of 190 NSCLC patients and 200 healthy controls were evaluated for polymorphic analysis of -174 G/C and -634 C/G by PCR-RFLP followed by DNA sequencing. A significant association was observed in the genotypic and allelic distribution of IL-6 -174 G/C in the NSCLC group as compared to control group [OR = 2.7 (1.77-4.11), p < 0.0001]. Smokers with the -174C allele were found to be significantly associated with NSCLC (p = 0.01), while 634C/G SNP showed an inverse relation [OR-0.4, p < 0.0001]. The present investigation revealed a significant association of the IL6 -174 G/C gene promoter polymorphism with NSCLC, and thus, the IL-6 -174G/C genotype can be considered as one of the biological markers in the etiology of NSCLC.

XRCC3 Thr241Met gene polymorphism and risk of colorectal cancer in Kashmir: a case control study.

XRCC (X-ray cross-complementing group) genes contribute to important DNA repair mechanisms that play roles in the repair of single strand breaks (SSBs) induced by a variety of external and internal factors, including ionizing radiation, alkylating agents and reactive oxygen species. These repair genes have a pivotal role in maintaining genomic stability through different pathways of base excision repair (BER). The aim of this study was to investigate the XRCC3 Thr241Met gene polymorphism in colorectal cancer (CRC) in Kashmir. We investigated the genotype distribution of XRCC3 gene in 120 CRC cases in comparison with 150 healthy subjects and found a significant association between XRCC3 genotypes and CRC (p≤0.05). Both heterozygous genotype (Thr/Met) as well as homozygous variant genotype (Met/Met) were moderately associated with elevated risk of CRC [OR=2.53; OR=2.29 respectively]. Also, Thr/Met and Met/Met genotypes demonstrated a significant association with the risk of CRC (p=0.003). This study displayed a significantly elevated risk for CRC in individuals with XRCC3 Thr/Met and Met/Met Genotype of about 2.5 times that with the Thr/Thr wild genotype.

DNA repair gene--XRCC1 in relation to genome instability and role in colorectal carcinogenesis.

Colorectal carcinogenesis is a multifactorial and multi-gene process, involving 3 major genetic instability pathways: chromosomal instability, microsatellite instability and CpG island methylator phenotype. Inefficient DNA repair is one of the causes of genetic instability leading to tumorigenesis. Defects in DNA repair genes are associated with cancer development. The XRCC1 gene is an important DNA repair genes and forms the component of several different damage recovery pathways, including base excision repair and single-strand breaks repair - the processes frequently involved in cancer transformation. In this review we have shed light on the structure and functioning of the XRCC1 gene and its protein, and the role played by XRCC1 in colorectal carcinogenesis.

Stroke-induced immune depression-a randomized case control study in Kashmiri population of North India.

BACKGROUND: Stroke leads to transient immunedepression, which leads to increased incidence of poststroke infections. Because infection is one of the most common causes of increased mortality in patients with stroke, this study was undertaken to document immunedepression after stroke in our population. METHODS: A case-controlled study wherein 39 patients with acute ischemic stroke in the age group of 18 and 60 years without any evidence of previous immunedepression were included. Interleukin 6 (IL-6) and interleukin 10 (IL-10) levels were checked in plasma in both the groups on day 3 and day 45. Also Cortisol and epinephrine levels were checked in the urine samples collected on day 3 and day 8. RESULTS: No significant difference was seen between the IL-6 and the IL-10 levels in samples collected on day 3 between the controls and cases, whereas Cortisol and norepinephrine were significantly raised in samples collected on day 3 in cases who developed infection as compared with controls. CONCLUSIONS: The higher levels of urinary cortisol and norepinephrine were observed in patients with stroke who developed infections, which indirectly reflected increased amount of stroke related stress. Furthermore, the levels of plasma IL-6 and IL-10 were also elevated in the same group of patients, which means transformation of immunecompetence to immunedepression, which is responsible for higher mortality. Subsequently on recovery from infection the plasma levels of interleukins and urinary cortisol and norepinephrine did not show any difference, which indirectly means recovery of the immune system on recovery from acute stage of stroke. Mortality in the patients with infection was increased than controls.

COX-2 overexpression and -8473 T/C polymorphism in 3' UTR in non-small cell lung cancer.

A new class of compounds targeting cyclooxygenase 2 (COX-2) together with other different clinically used therapeutic strategies has recently shown a promise for the chemoprevention of several solid tumors including lung cancer. The aim was to study the possible role of COX-2 -8473 T/C NP and its expression in the pathogenesis of non-small cell lung cancer. One hundred ninety non-small cell lung cancer (NSCLC) patients and 200 healthy age-, sex-, and smoking-matched controls were used for polymorphic analysis, and 48 histopathologically confirmed NSCLC patients were analyzed for COX-2 messenger RNA (mRNA) and protein expression. Our results showed that the frequencies of variant genotypes 8473 CT/CC were significantly less common in the cases (30.0%) than in the controls (36%), suggesting that the 8473 C variant allele is related with lower susceptibility in NSCLC (OR = 0.79, 95% CI 0.54-1.4). However, the frequency of COX-2 -8473 TC and CC genotypes were significantly associated with age in NSCLC (P = 0.02). Quantitative real-time expression analysis showed a significant increase in the COX-2 mRNA in tumor tissues as compared to their adjacent normal tissues [delta cycle threshold (ΔCT) = 9.25 ± 4.67 vs 5.63 ± 3.85, P = 0.0001]. Multivariate logistic regression analyses revealed that the COX-2 expression was associated significantly with age (P = 0.044). Also, an increasing trend was observed in stages I and II and in female patients compared to stages III and IV and male patients, respectively, but no statistical significance was observed. However, COX-2 mRNA expression shown no association with the -8473 C variant allele. Our findings indicate that the COX-2 T8473C polymorphism may contribute to NSCLC cancer susceptibility in the Kashmiri population, while our expression analysis revealed a significant increase of COX-2 in tumor tissues as compared to their adjacent normal tissues, suggesting that it could become an important therapeutic marker in NSCLC in the future.

RAD51 G135C gene polymorphism and risk of colorectal cancer in Kashmir.

RAD51 - a DNA double-strand breaks repair gene plays an important role in homologous recombination, a process frequently involved in cancer transformation. The aim of this study was to compare the distribution of the genotype of the RAD51 G135C polymorphism between colorectal cancer (CRC) patients and controls. We also tested the association between the G135C polymorphism of the RAD51 gene and the risk of CRC, and various clinicopathological parameters. Polymorphism was evaluated by restriction fragment length polymorphism PCR in 100 CRC patients and 120 age-matched and sex-matched controls. There was a significant association between RAD51 genotypes and CRC cases (P<0.05). Also, the GC genotype was associated with an increased risk of CRC (odds ratio >3.84). Our results suggest that the G135C polymorphism of the RAD51 gene is associated with an increased risk of CRC in our population.

Rheumatoid arthritis and genetic variations in cytokine genes: a population-based study in Kashmir Valley.

OBJECTIVE: The aim of our study was to determine the genetic associations between polymorphisms of the IL1ß gene (-511C/T and +3953C/T) and IL6 gene (-174G/C) with disease susceptibility and severity in patients with rheumatoid arthritis (RA) in ethnic Kashmiri population. METHODS: Allele and genotype frequencies of IL1ß -511 C/T, IL1ß +3953 C/T and IL6 -174 G/C polymorphisms were compared between 150 RA patients and 200 healthy controls by using PCR-RFLP method. RESULTS: We did not find any significant association between IL1b +3953 C/T and IL6 -174 G/C polymorphism and Rheumatoid Arthritis risk (p>0.05), but IL1ß +3953 CT genotype was associated significantly with increased SJC and ESR and IL6 -174 GG genotype was associated significantly with increased ESR. However IL1b -511C/T polymorphism was significantly associated with rheumatoid arthritis risk and the carriers of IL1ß -511 'C' allele (CC and TC genotypes) appeared to have lower risk for RA development. CONCLUSION: Our findings suggest that the IL1b -511 'C' allele has a protective role from disease development. Furthermore our results suggest a possible role of IL1b +3953 CT and IL6 -174 GG genotypes as disease activity markers of rheumatoid arthritis.

H. pylori infection, inflammation and gastric cancer.

INTRODUCTION: A strong association between chronic infection, inflammation, and cancer has been suggested. DISCUSSION: Helicobacter pylori, a microaerophilic gram negative bacterium, infects about half the world's population. It has been defined as a definitive carcinogen in the pathogenesis of gastric cancer. H. pylori evades the host immune responses and persists in the stomach leading to gastritis gastric atrophy and sometimes gastric cancer. CONCLUSION: Chronic H. pylori infection causes gastric cancer via two mechanisms: the presence of virulence factors and the induction of chronic inflammation which ultimately leads to neoplastic transformation.