Smoking Behavior and Risk of Helicobacter Pylori Infection,Gastric Atrophy and Gastric Cancer in Japanese

Although many studies have shown that smoking is an established risk factor for gastric cancer, relativelyfew studies have investigated on which step smoking has effects in Helicobacter pylori (H. pylori) related gastriccarcinogenesis. In this study we investigated the association of smoking with risk of three steps leading to gastriccancer: H. pylori infection, gastric atrophy, and gastric cancer. Among the participants who visited Aichi CancerCenter Hospital from year 2001 to 2005, 583 cases diagnosed as gastric cancer and age-and sex-frequency-matched1,742 cancer free controls were sampled, from whom those without serum samples or without information aboutsmoking habit were excluded, leaving 576 cases and 1,599 controls eligible for the analyses. Anti- H. pylori IgGantibody and serum pepsinogens (PG) were measured to detect H. pylori infection and gastric atrophy. Smokingstatus was asked by a self-administered questionnaire. The odds ratio (OR) of H. pylori infection, as well as theOR of gastric atrophy among the H. pylori seropositive controls was not significant for smokers. The age- andsex-adjusted OR of gastric cancer was significantly elevated relative to the subjects with gastric atrophy: OR=1.62(95% confidence interval (CI), 1.19-2.22; P=0.002) for ever smokers and 2.52 (1.75-3.64; P<0.001) for currentsmokers, relative to never smokers. This study revealed that smoking behavior contributed to the increased riskof gastric carcinogenesis from gastric atrophy, and had little influence on H. pylori infection or gastric atrophydevelopment.     

Gastric Cancer: the Roles of Diet,Alcohol Drinking,Smoking and Helicobacter pylori in Northeastern Thailand

The incidence of gastric cancer in the countries of South East Asia is variable, ranging from age-standardized ‍rates of 20.9/105 (men) and 10.4/105 (women) in Hanoi, Vietnam to 4.1/105 (men) and 2.1/105 (women) in Khon Kaen, ‍Thailand. The reasons for these differences are unknown. Possible explanations are differences in dietary habits, ‍alcohol drinking, smoking and/or the prevalence of infection with Helicobacter pylori (H. pylori). A case-control ‍study was conducted in Khon Kaen, Thailand, to study the role of these factors in gastric cancer carcinogenesis. 131 ‍gastric cancer cases and 262 matched controls were recruited for the study. Information on dietary habits, alcohol ‍drinking and smoking were collected by a structured questionnaire. Blood samples were available from 111 cases ‍and 232 controls for H. pylori assay. Using an unconditional logistic regression model controlling for age and sex, we ‍assessed the effects of dietary habits, alcohol drinking, smoking and H. pylori infection on the risk of gastric cancer. ‍A high intake of salt (OR=1.8; 95%CI 1.1-3.0) and fermented foods (OR=1.9; 95%CI 1.1-3.3) was found to be ‍associated with an increased risk. Preference for spicy food was not associated with gastric cancer risk in this ‍population. Although there were negative associations between gastric cancer and vegetable and fruit intake, they ‍were rather weak (OR 0.8 for both) and non significant. There were also weak (non-significant) associations with ‍smoking and alcohol consumption, and no association with H. pylori infection (OR=0.6; 95%CI 0.4-1.0). Infection of ‍H. pylori was associated with various indicators of crowding. ‍     

Risk of gastric cancer among smokers infected with Helicobacter pylori

Infection with the gastric bacterium Helicobacter pylori (in particular infection with CagA-positive strains) and smoking have been identified as risk factors for the development of gastric cancer. Both risk factors are typically acquired early in life and prevail over decades if not for life. We assessed the individual and joint impact of both risk factors on gastric cancer risk in a population-based case-control study from Germany including 71 patients with histologically verified gastric cancer and 363 patients with colorectal cancer who served as controls. Information on smoking and potential confounding factors was collected by standardized interviews. H. pylori infection was measured serologically by immunoglobulin G antibody titers against H. pylori. In addition, antibodies against the CagA antigen were determined by Western blot. Twenty-seven percent of cases compared with 15% of controls were smokers, and 43% of cases compared with 23% of controls were infected with CagA-positive H. pylori strains. After control for potential confounders, the relative risk of gastric cancer was 2.6 (95% CI 1.2-5.7) for nonsmoking subjects with CagA-positive H. pylori infections and 7.2 (95% CI 2.2-23.6) for smoking subjects with CagA-positive H. pylori infections compared with subjects without these risk factors. The corresponding relative risks for noncardia gastric cancer were 6.1 ( 95% CI 2.3-16.5) and 16.6 (95% CI 4.3-64.2). We conclude that smoking subjects with CagA-positive H. pylori infections have a strongly increased risk of gastric cancer and may be an important group for targeting efforts of prevention and early detection.     

Association between serum pepsinogens and polymorphismof PTPN11 encoding SHP-2 among Helicobacter pylori seropositive Japanese

Helicobacter pylori (H. pylori) plays a crucial role in the development of gastric atrophy and cancer, and cagA-positive strains, which are universal in Japan, increase the risk of these outcomes substantially. The CagA protein is injected from attached H. pylori into gastric epithelial cells and undergoes Src-dependent tyrosine phosphorylation and activation of the eukaryotic phosphatase SHP-2. The CagA/SHP-2 interactions elicit cellular changes that increase the risk of carcinogenesis. We investigated the association of a frequent single nucleotide polymorphism (SNP; JST057927; G-to-A) in the PTPN11 gene that encodes SHP-2 with gastric atrophy and gastric cancer in Japan. Gastric atrophy was assessed by measuring serum pepsinogen I and II levels. The subjects comprised 454 healthy controls (126 males; mean age, 58.4) and 202 gastric cancer cases (134 males and 68 females; mean age, 66.7). All gastric cancer cases and 250 (55%) controls were H. pylori seropositive; 179 (89%) of the gastric cancer cases had gastric atrophy compared to 137 (55%) of the H. pylori seropositive controls (p < 0.001). Among HP seropositive controls compared to the common PTPN11 G/G genotype, the odds ratio of atrophy was nonsignificantly reduced with the G/A genotype (0.70; 95% CI = 0.39-1.25) and significantly reduced with the A/A genotype (0.09; 95% CI = 0.01-0.72). Lower risk for gastric atrophy had a gene-dose association with the A allele (p = 0.01, trend test). There was a clear deficiency of the A/A genotype in those with atrophy compared to those without (1 subject in the gastric atrophy group vs. 8 in the group without). Cancer cases differed from controls in frequencies of PTPN11 G/A genotype only because of a higher prevalence of atrophy among the cancer cases. The G/A SNP in the PTPN11 gene appears to be a risk factor for gastric atrophy in subjects infected with cagA-positive H. pylori. This may explain why only a proportion of CagA-positive individuals develop gastric atrophy and gastric cancer, even though infection with cagA strains is universal in Asian countries such as Japan. The functional consequences of the G/A polymorphism remain to be elucidated.     

Genetic factors involved in the development of Helicobacter pylori-related gastric cancer

Developmental process to gastric cancer by Helicobacter pylori infection consists of three steps: (1) H. pylori infection; (2) gastric atrophy development; and (3) carcinogenesis. In each step, genetic traits may influence the process, interacting with lifestyle. In the step of H. pylori infection, two lines of genetic polymorphisms were assumed: one influencing gastric acid inhibition interacting with smoking, and the other concerning innate immune response attenuation. The former includes functional polymorphisms of IL-1B (C-31T or tightly linked T-511C), and TNF-A (T-1031C and C-857T), and the latter possibly includes NQO1 C609T. In the step to gastric atrophy, polymorphisms pertaining to the signal transduction from cytotoxin-associated gene A (PTPN11 A/G at intron 3) and to T-cell responses (IL-2 T-330G and IL-13 C-1111T) were hypothesized. There are a limited number of epidemiological genotype studies on the final step of literal carcinogenesis, potentially interacting with smoking, a low vegetable and fruit intake, and salty foods, the well-documented risk factors. In past case-control studies on the associations between genotype and gastric cancer risk, the cases consisted of H. pylori-related and unrelated gastric cancer patients and the controls consisted of individuals including the uninfected (H. pylori unexposed and exposed) and the infected with and without gastric atrophy. Accordingly, it was not clear whether the observed risk was for H. pylori-related or -unrelated gastric cancer, nor which step was involved in the observed associations even when nearly all cases were H. pylori-related. In order to elucidate the genetic traits of H. pylori-related gastric cancer, stepwise evaluation will be required.     

Salt Taste Preference,Sodium Intake and Gastric Cancer in China

Aim: The risk factors mostly strongly associated with gastric cancer are gastric bacteria Helicobacter pyloriand diet. By using a case-control study among residents in China, we examined the association between sodiumintake, presence of H,pylori, and gastric cancer risk. Methods: A population-based case-control study including235 cases and 410 controls were used. Potential risk factors of gastric cancer were interview for cases and controlsby questionnaire, salt taste preference was measured for all subjects, and IgG antibodies to H,pylori was usedfor H.pylori infection. Risk measures were calculated using unconditional logistic regression. Results: H.pyloriinfection and smoking increased the risk of gastric cancer, with the OR(95%CI) of 1.91(1.32-2.79) and 1.47(1.05-2.05), respectively. Dietary sodium intake independently increased the risk of gastric cancer. Participants withthe highest sodium intake(>5g/day) had a high gastric cancer risk [OR(95%CI)= 3.78(1.74-5.44)]. Participantswith the salt taste preference at 7.3g/L and ≥14.6g/L showed higher risk of gastric cancer [OR(95%) for 7.3g/Land ≥14.6g/L were 5.36(2.72-10.97) and 4.75(2.43-8.85), respectively]. A significantly interaction was foundbetween salt taste preference and H.pylori infection (p=0.037). Salt taste preference was significantly correlatedwith sodium intake (Correlation coefficient=0.46, p<0.001). Conclusion: Salt taste preference test could be asimple way to evaluate an inherited characteristic of sodium intake, and our study confirms the gastric canceris associated with sodium intake and H.pylori.     

Role of Helicobacter pylori CagA+ strains and risk of adenocarcinoma of the stomach and esophagus

Infection with Helicobacter pylori (H. pylori), especially CagA+ strains, has been associated with an increased risk of noncardia gastric adenocarcinoma. The relationship with junctional cancer (adenocarcinomas of the esophagus and gastric cardia combined) has not been adequately investigated, although some studies have reported a reduced risk associated with H. pylori and CagA seroseropositivity. We investigated this question in a subset of cases and controls from a recently completed, large population-based case-control study of gastric and esophageal adenocarcinomas in Los Angeles County. Using established antigen-specific ELISAs, serum IgG antibodies to H. pylori whole-cell antigens (Helico-G) and CagA were measured in population controls (n = 356) and patients with incident esophageal adenocarcinoma (n = 80), gastric cardia cancer (n = 87) or distal gastric cancers (noncardia gastric adenocarcinoma) (n = 127). After controlling for demographic characteristics (age, gender, race, birthplace, education), smoking and body mass index, seropositivity for H. pylori was associated with a statistically significant increased risk of distal gastric cancer (adjusted odds ratio [OR] = 1.85, 95% confidence interval [CI] = 1.03, 3.32) but the risk of junctional cancer was not increased (adjusted OR = 1.26, 95% CI = 0.82, 1.94). The risk of junctional cancer was not changed when CagA and H. pylori were both considered, but the risk of distal gastric cancer was further increased. Subjects who were seropositive for both CagA and H. pylori compared to those who were seronegative for H. pylori showed a risk of 2.20 (95% CI = 1.13, 4.26) for distal gastric cancer and 0.86 (95% CI = 0.47, 1.59) for junctional cancer. Although tests for interaction between smoking and H. pylori were not statistically significant for junctional or distal gastric cancers, risk for both tumor types tended to be higher among current smokers who were also H. pylori seropositive. In conclusion, we find no evidence that infection with CagA+ strains of H. pylori reduces risk of esophageal and gastric cardia adenocarcinoma in this population. Our findings confirm the positive association between risk of distal gastric cancer and infection with H. pylori infection, especially CagA+ strains.     

Helicobacter pylori infection-negative gastric cancer in Japanese hospital patients: incidence and pathological characteristics

We used Helicobacter pylori sero-positivity and mucosal atrophy as detected by the serum pepsinogen method to identify H. pylori infection-negative gastric cancer patients with or without atrophy. One hundred and six of 748 (14.2%) primary gastric cancer patients were infection-negative by a serum antibody detection system. Further, 121 (16.2%) of the 748 were negative for gastric mucosal atrophy by the pepsinogen method, of whom 15/748 (2.0%) were H. pylori-negative by pepsinogen I level (>70 ng/mL) and pepsinogen I/II ratio (>3.0). Twenty-seven of 782 (3.6%) gastric cancer patients were H. pylori-negative by antibodies and severe atrophy as determined by pepsinogen I level (<30 ng/mL) and pepsinogen I/II ratio (<2.0). H. pylori-negative gastric cancer patients with severe atrophy likely had a previous infection. These results indicate that the actual number of H. pylori-negative patients is 2.0% at minimum and 10.6% (14.2% minus 3.6%) at maximum in the general Japanese population. Five of 15 (33%) cases displaying neither anti-H. pylori antibodies nor atrophy were intestinal-type and 10 (67%) were diffuse-type adenocarcinomas. Thirteen surgical patients with primary gastric cancer displaying neither antibodies nor mucosal atrophy were further analyzed for pathological and phenotypic characteristics. The mucin phenotype was divided into four gastric, five gastric and intestinal, two intestinal and two null types, independent of histological classification. Intestinal phenotype elements were detected by Cdx2 immunohistochemical methods in nine of 13 (70%) cases examined. We conclude that a small fraction of gastric cancer patients displayed multifactorial carcinogenesis without H. pylori infection, indicating that gastric cancer risk still exists in the absence of H. pylori infection, at an incidence of 2.0% at minimum and 10.6% at maximum in the general Japanese population.     

Helicobacter pylori infection on the risk of stomach cancer and chronic atrophic gastritis.

Helicobacter pylori infection is associated with gastric adenocarcinoma. However, the mechanisms of this interaction are still unclear. This study was conducted to explore the effects of H. pylori infection on early and late stage gastric carcinogenesis. This study included 134 patients with adenocarcinoma of the stomach (ACS), 67 patients with chronic atrophic gastritis (CAG), and 65 normal controls recruited at Memorial Sloan-Kettering Cancer Center (MSKCC) from November 1, 1992 to November 1, 1994. Epidemiologic data were collected by a modified National Cancer Institute Health Habits History Questionnaire. H. pylori infection was diagnosed by pathological evaluation. Risk factors were analyzed using logistic regression. The odds ratio (OR) associated with H. pylori infection was 10.4 [95% confidence interval (CI): 2.6-41.6] for CAG and 11.2 (95% CI: 2.5-50.3) for gastric cancer in comparison with normal controls, with adjustment for pack-years of smoking, alcohol drinking, body mass index, total caloric intake, dietary fat and fiber intake, and Barrett's esophagus. But H. pylori infection was not associated with risk of stomach cancer when patients with stomach cancer were compared with patients with CAG (OR = 0.6, 95% CI: 0.3-1.3) after controlling for potential confounding variables. This association was persistent when only patients with both gastric cancer and chronic gastritis were considered as cases and patients with CAG were considered as controls (OR = 0.7, 95% CI: 0.3-2.0) in the multivariate analysis. Our results suggest that H. pylori infection may be involved in the early stage of development of CAG, but not in the development of stomach cancer from CAG, and indicate that strategies for prevention of stomach cancer should target the early stage to eliminate H. pylori infection in high-risk populations.     

Sodium intake, salt taste and gastric cancer risk according to helicobacter pylori infection, smoking, histological type and tumor site in china

Aim: The risk factors mostly strongly associated with gastric cancer are gastric bacteria Helicobacter pyloriand diet. Using a case-control study among residents in Jinan, we examined the association between the salt tasteand gastric cancer according to H. pylori infection, smoking and histological type as well as tumor site. Methods:This population-based case-control study included 207 cases and 410 controls. Data on potential risk factors ofgastric cancer were obtained by interview of cases and controls with a questionnaire, salt taste preference wasmeasured for all subjects, and IgG antibodies to H. pylori were applied to assess infection. Risk measures weredetermined using unconditional logistic regression. Results: The proportions of salt taste at intervals of 1.8-7.2g/L and ≥7.2 g/L were significantly higher in cases than controls, with ORs of 1.56 (1.23-3.64) and 2.03 (2.12-4.11), respectively, subjects with high salt intake having an elevated risk for gastric cancer when infected withH. pylori. Significant modification by smoking and tumor site was observed across the different measures of saltintake, the highest salt taste showed higher cancer risk in ever smokers or with non-cardia cancers. Conclusion:Our study supports the view that high intake of sodium is an important dietary risk factor for gastric cancer,with a synergistic effect found between salt and H.pylori and smoking, dependent on the tumor site.     

DNMT3a rs1550117 Polymorphism Association with Increased Risk of Helicobacter pylori Infection

Background: DNA methyltransferase-3a (DNMT3a) plays significant roles in embryogenesis and the generationof aberrant methylation in carcinogenesis. This study aimed to investigate associations between single nucleotidepolymorphisms (SNPs) of the DNMT3a gene and risk of Helicobacter pylori infection, gastric atrophy and gastriccancer. Methods: The subjects comprised 447 patients with gastric cancer; 111 individuals with gastric atrophyand 961 healthy controls. Two SNPs (rs1550117 and rs13420827) of the DNMT3a gene were genotyped by Taqmanassay. DNMT3a expression was analyzed in cancer tissues from 89 patients by tissue microarray technique. Oddsratio (ORs) and 95% confidence intervals were calculated by multivariate logistic regression. Results: Amonghealthy controls, risk of H.pylori infection was significantly higher in subjects with the rs1550117 AA genotype,compared to those with GG/AG genotypes of DNMT3a [OR=2.08, (95%CI: 1.02-4.32)]. However, no significantcorrelation was found between the two SNPs and risk of developing gastric atrophy or gastric cancer. In addition,no increase in DNMT3a expression was observed in the gastric cancer with H.pylori infection. Conclusions:This study revealed that DNMT3a rs1550117 polymorphism is significantly associated with an increased risk ofH. pylori infection, but did not support any evidence for contributions of DNMT3a rs1550117 and rs13420827to either gastric atrophy or gastric cancer. The biological roles of DNMT3a polymorphisms require furtherinvestigation.     

No Association between the CDX2 G543C Polymorphism and Risk of Gastric Atrophy and Cancer

Ectopic expression of CDX2 in the stomach is closely associated with chronic Helicobacter pylori (H. pylori)infection and intestinal metaplasia. Whether CDX2 has tumor suppression or tumorigenesis potential remainsto be elucidated. In this study, we investigated the association between the CDX2 G543C polymorphism (silentmutation) and the risk for H. pylori-induced gastric atrophy and cancer as well as H. pylori infection, using 454Japanese subjects undergoing a health checkup and 202 gastric cancer patients. The frequency of the minor allelewas the same as previously reported in China, but different from that reported in England. CDX2 G543C wasnot associated with risk of H. pylori infection, gastric atrophy, or gastric cancer, although the point estimate fornon-cardiac differentiated gastric cancer as compared to controls with gastric atrophy was 2.22 (95%CI=0.17-29.4). In conclusion, our results indicate that the CDX2 G543C polymorphism is unlikely to affect the H. pyloriinfection-gastric atrophy-gastric cancer sequence.     

Gastric adenocarcinoma and Helicobacter pylori infection.

Helicobacter pylori infection, thought to be causally related to chronic gastritis, may also be associated with an increased risk of gastric cancer. To determine whether an association with gastric cancer does exist, we retrospectively evaluated serum samples from 69 patients with histologically confirmed gastric adenocarcinoma (32 with cancer at the cardia and 37 with cancer at other sites) and from 218 patients with one of three categories of nongastric cancers, with other gastric cancers, or with benign gastric neoplasms. These samples were compared with samples from 252 cancer-free control subjects, a group comprising 76 asymptomatic volunteers and 176 persons with nonmalignant disorders. Serum samples collected from cancer patients prior to surgery and from cancer-free controls were tested for antibodies to H. pylori by using a highly sensitive and specific IgG enzyme-linked immunosorbent assay. The risk of H. pylori infection in the case patients relative to the control subjects was estimated with the use of multivariate logistic regression analysis to adjust for potential confounding variables. Antibodies to H. pylori were detected in 65% of the patients with noncardia gastric cancer but in only 38% of the patients with gastric cancer located at the cardia. A significant association was found between H. pylori infection and noncardia gastric cancer (odds ratio = 2.67; 99% confidence interval = 1.01-7.06). Within the subset of patients with noncardia gastric cancer, a statistically nonsignificant tendency existed for those with the intestinal versus the diffuse histologic type of noncardia gastric cancer to have a higher risk of H. pylori infection. Our results support the hypothesis of a relationship between H. pylori infection and the development of noncardia gastric adenocarcinoma.     

SNPs of Excision Repair Cross Complementing Group 5 and Gastric Cancer Risk in Chinese Populations

We conducted a case-control study to determine the association between several potential SNPs of excisionrepair cross complementing group 5 (XPG) and gastric cancer susceptibility, and roles of XPG polymorphismsin combination with H.pylori infection in determining risk of gastric cancer. In our study, we collected 337 newlydiagnosed gastric cancer cases and 347 health controls. Three SNPs of XPG, rs2296147T>C, rs2094258C>Tand rs873601G>A, were genotyped using the Taqman real-time PCR method with a 7900 HT sequence detectorsystem. H. pylori infection was diagnosed by ELISA. By multivariate logistic regression analysis, the rs2296147CC genotype was associated with a decreased risk of gastric cancer (OR=0.52, 95% CI=0.27-0.97), and rs2094258TT was associated with elevated risk (OR=2.13, 95% CI=1.22-3.35). Positive H.pylori individuals with rs2094258TT genotypes demonstrated increased risk of gastric cancer (OR=2.13, 95% CI=1.22-3.35), while rs2296147 CCwas associated with lower risk among patients with negative H.pylori (OR=0.45, 95%CI=0.22-0.89). Our findingssuggested that XPG polymorphisms might contribute to risk of gastric cancer among Chinese populations, butthe effect needs to be further validated by larger sample size studies.     

Helicobacter pylori strain types and risk of gastric cancer: a case-control study.

The aim of this novel endoscopy clinic-based case-control study was to explore the influence of different Helicobacter pylori strain types on the risk of gastric adenocarcinoma using isolated bacterial strains, tissue samples, and sera. We included 72 cases with gastric adenocarcinoma and 324 age- and sex-matched controls. Histological characterization, culture, molecular typing of H. pylori genes by PCR (cagA/vacA), conventional IgG ELISA, and immunoblotting (Western blot) for the CagA and VacA proteins were performed. With four tests combined, H. pylori infection was detected in 57 (79%) cases and 213 (66%) controls. A positive association between H. pylori infection and gastric cancer risk was found [odds ratio (OR), 2.1; 95% confidence interval, 1.1-3.9]. Type I (OR, 1.8), intermediate (OR, 2.0), and type H (OR, 0.2) strains of H. pylori presented different serum antibody levels and different levels of association with gastric cancer. Our case-control study, based on molecular characterization and serology, provides further evidence that infection by more virulent strains of H. pylori and the presence of antibodies toward the CagA protein can be used as markers for an increased risk of gastric adenocarcinoma and that the strain types of H. pylori could be used in the future to determine disease outcome.     

Low serum pepsinogen I and pepsinogen I/II ratio and Helicobacter pylori infection are associated with increased risk of gastric cancer: 14-year follow up result in a rural Chinese community

The correlation between low serum PG level and H. pylori infection with the development of gastric cancer has caused considerable concerns all over the world. Some authors exclaimed that gastric cancer developed only in patients infected with H. pylori, whereas the other had different findings. In this study, 1,501 adult local residents with determined serum PG levels and anti H. pylori IgG status were followed for 14 years for the development of gastric cancer in a rural community with high risk of gastric cancer in Hebei Province, China. The results showed the accumulated gastric cancer incidence in the subjects with abnormal PG level and those with H. pylori infection were all significantly higher than that in the corresponding normal controls (53.9‰ vs. 12.7‰, p < 0.05 and 23.1‰ vs. 5.93‰, p < 0.05). The highest gastric cancer incidence was seen in the subjects with both abnormal serum PG and positive H. pylori (56.0‰), and followed by the subjects with abnormal PG and negative H. pylori (47.6‰) and those with normal serum PG and positive H. pylori (18.4‰). The abnormal serum PG level (OR 3.029) and H. pylori infection (OR 4.345) were all risk factors for the development of gastric cancer. The results suggested that the subjects with abnormal serum PG level and/or positive H. pylori infection in the rural area of China were all high risk population for gastric carcinoma and the subjects with both abnormal serum PG and positive H. pylori infection were at especially high risk for the development of gastric carcinoma.     

No Association of an SDHC Gene Polymorphism with Gastric Cancer

It is widely reported that reactive oxygen species (ROS) cause apotosis and carcinogenesis. Marked infiltration ofactivated leukocyte and enhanced production of ROS appear to occur in the gastric mucosa infected with Helicobacterpylori (H. pylori). The previous studies reported that the mutation of the succinate dehydrogenase subunit C (SDHC)gene caused the increase in superoxide anion (O2-) and oxidative stress. To extend these findings, we epidemiologicallyinvestigated the association of a SDHC polymorphism at 3’-untranslated region of exon 6 (JST173800) with H. pyloriinfection, gastric atrophy and gastric cancer risk in Japan. The subjects consisted of 454 health checkup examineeswithout a history of cancer and 202 gastric cancer patients. The SDHC polymorphism was not associated with H.pylori infection seropositivity, gastric atrophy, and cancer risk in this study. Although the polymorphism at the 3’-untranslated region could be hypothesized to be functional, this study did not demonstrate any significant associationof the SDHC gene polymorphism with gastric atrophy and cancer.     

Effect of Xeroderma Pigmentosum Complementation Group FPolymorphisms on Gastric Cancer Risk and Associations withH.pylori Infection

We conducted a hospital case-control study by genotyping four potential functional single nucleotidepolymorphisms (SNPs) to assess the association of Xeroderma pigmentosum complementation group F (XPF)with gastric cancer susceptibility, and role of XPF polymorphisms in combination with H.pylori infection in riskdefinition. A total of 331 patients with gastric cancer and 355 controls were collected. Four SNPs of XPF, rs180067,rs1799801, rs2276466 and rs744154, were genotyped by Taqman real-time PCR method with a 7900 HT sequencedetector system. The gastric cancer patients were more likely to have smoking habit, a family history of cancerand H.pylori infection. We did not find any significant difference in the genotype distributions of XPF rs180067,rs1799801, rs2276466 and rs744154 between cases and controls. However, multivariate logistic analysis showeda non-significant decreased risk in patients carrying rs180067 G allele, rs1799801 T allele or rs2276466 T allelegenotypes. A non-significant increased risk of gastric cancer was found in individuals carrying the rs744154 GGgenotype. Stratification by H.pylori infection and smoking was not significantly different in polymorphisms ofXPF rs180067, rs1799801, rs2276466 and rs744154. The four XPF SNPs did not show significant interaction withH.pylori infection and smoking status (P for interaction was 0.35 and 0.18, respectively). Our study indicatedthat polymorphisms in rs180067, rs1799801, rs2276466 and rs744154 may affect the risk of gastric cancer butfurther large sample size studies are needed to validate any association.     

Helicobacter pylori Infection, Serum Pepsinogen Level and Gastric Cancer: A Case-Control Study in Japan

We conducted a case-control study to evaluate the effect of Helicobacter pylori (HP) infection on the risk of gastric cancer in Tokyo, Japan. The sera at the time of diagnosis from 282 gastric cancer cases and 767 sex- and age-matched cancer-free controls were tested for the presence of anti-HP IgG antibody (HM-CAP ELISA kit) and serum pepsinogen (PG) level (PG I and PG II Riabead). No significant association was observed in all sets [matched odds ratio (OR)=1.04, 95% confidence interval: 0.73–1.49]. In subgroup analyses, however, an association was suggested in females [OR=1.57], a younger population (<50 years) [OR=1.86], early cancer [OR=1.53] and small cancer (<40 mm) [OR=1.55]. Furthermore, we observed a tendency for odds ratios to decrease with an increase in age or cancer growth (depth of tumor invasion and tumor size). Considering that the spontaneous disappearance of HP due to extended mucosal atrophy may lead to these decreasing odds ratios, we applied the conditional logistic model adjusted for the PG I/II ratio as a measure of atrophic gastritis. This analysis showed a positive association with HP infection in all sets [OR=1.69; 1.01–2.81], distal cancer [OR=1.88; 1.07–3.31] and intestinal-type cancer [OR=3.76; 1.39–10.18]. We concluded that the risk of cancer associated with HP infection may be underestimated in studies with cross-sectional exposure because of spontaneous disappearance of HP due to extended mucosal atrophy.     

Outcome of Intestinal Metaplasia in Gastric Biopsy of Patients with Dyspepsia in Guilan Province,North Iran

Background: It is generally accepted that gastric carcinomas are preceded by a sequential multistage processthat includes chronic gastritis, gastric atrophy, usually with intestinal metaplasia (IM), and dysplasia. This seriesof changes in gastric carcinogenesis is often initiated by Helicobacter pylori (H pylori) infection. The aim of thepresent study was determination of gastric histopathologic changes in IM patients after at least one year in Guilanprovince, Iran. Materials and Methods: This case-series study was conducted in Guilan Gastrointestinal and LiverDisease Research Center (GLDRC) during 2010 to 2011. Gastric biopsy was performed for all 71 known cases ofIM and precanceric lesions including gastric atrophy, IM, dysplasia and H pylori infection were determined afterat least one year. Results: Of the total of 71 patients with established IM who were enrolled, 50 had complete-typeIM and 21 had incomplete-type IM. Fifty two people had H pylori infection. H pylori eradication was achievedin 39 patients (75%). Secondary pathology findings of patients with IM were complete metaplasia (39.4%),incomplete metaplasia (32.4%), dysplasia (23.9%) and other precanceric lesions (4.2%). Dysplasia (20%vs 33%)occurred in patients who had complete and incomplete IM at baseline respectively (p>0.05). Age, gender, familyhistory of gastric cancer(GC); smoking habits and NSAIDs use were not associated with gastric premalignantlesions in initial and secondary pathologies (p>0.05). The difference became statistically significant between Hpylori infection in patients with more than 3 years diagnostic intervals (p<0.05). Statistical difference betweeneradicators and non-eradicators was not significant. Conclusions: We found that incomplete IM increased therisk of subsequent dysplasia in this study.