Toll-like receptor 2 -196 to 174del polymorphism influences the susceptibility of Japanese people to gastric cancer

Toll like receptors (TLR) play important roles in the signaling of many pathogen-related molecules and endogenous proteins associated with immune activation. The –196 to –174del polymorphism affects the TLR2 gene and alters its promoter activity. We investigated the influence of the TLR2 –196 to –174del polymorphism on the occurrence of non-cardiac gastric cancer (NCGC) in a Japanese population. The study was carried out with 289 patients with NCGC, 309 non-cancer patients with abdominal discomfort and 146 healthy controls. The –196 to –174del TLR2 polymorphism was investigated using the allele-specific polymerase chain reaction method in all of the subjects. The –196 to –174del/del genotype of TLR2 showed a significantly higher frequency in NCGC patients than in healthy controls (adjusted odds ratio [OR] = 6.06; 95% confidence interval [CI] = 1.86–19.72). Similarly, the frequency of the –196 to –174del/del genotype was significantly higher among NCGC patients than in non-cancer patients (adjusted OR = 2.02; 95% CI = 1.22–3.34). The same genotype was associated with an increased risk of both intestinal (OR = 2.00, 95% CI = 1.12–3.60) and diffuse-type (OR = 2.05; 95% CI = 1.11–3.79) histopathology. There were no significant associations between TLR2 genotypes and tumor stage and anatomical location. Our data suggest that the –196 to –174del/del genotype of TLR2 may increase the risk of gastric cancer in the Japanese population. ( Cancer Sci 2007; 98: 1790–1794)     

No association between AICDA 7888 C/T polymorphism, Helicobacter pylori seropositivity, and the risk of atrophic gastritis and gastric cancer in Japanese

Background  

The aberrant expression of activation-induced cytidine deaminase (AICDA) was reportedly induced in gastric epithelial cells infected with cytotoxin-associated gene A (cagA)-positive Helicobacter pylori, resulting in the accumulation of alterations in the TP53 tumor suppressor gene in gastric cells. We investigated the association of the AICDA 7888 C/T polymorphism with H. pylori infection and the risk of gastric cancer and atrophic gastritis in Japanese subjects.     

The toll-like receptor 2 (TLR2) -196 to -174 del/ins polymorphism affects viral loads and susceptibility to hepatocellular carcinoma in chronic hepatitis C

Chronic hepatitis C virus (HCV) infection is a major risk factor for hepatocellular carcinoma (HCC). HCV proteins core and NS3 can bind to toll-like receptor 2 (TLR2) and trigger inflammatory responses. Polymorphisms in the TLR2 gene predispose to various forms of malignancy but have not been studied in HCV-associated HCC. Here, we investigated whether single nucleotide polymorphisms (SNPs), rs4696480, rs5743708, rs5743704 and the -196 to -174 del/ins polymorphism of the TLR2 gene affect the risk for HCC in chronic hepatitis C. The study involved 189 and 192 HCV genotype 1 infected patients with and without HCC, respectively, as well as 347 healthy controls. TLR2 alleles were determined by hybridization probe assays and allele-specific short fragment polymerase chain reaction on a LightCycler system. All TLR2 polymorphisms matched the Hardy-Weinberg equilibrium in each study group. Although TLR2 SNPs showed no effect, the frequency of the TLR2 -196 to -174 del allele was significantly higher in patients with HCV-associated HCC (22.5%) than in HCV-infected patients without HCC (15.6%, p = 0.016) and healthy controls (15.3%, p = 0.003). HCV-infected carriers of a TLR2 -196 to -174 del allele had significantly higher HCV viral loads than TLR2 -196 to -174 ins/ins homozygous patients (p = 0.031). Finally, in carriers of the TLR2 -196 to -174 del allele, stimulation of monocytes resulted in significantly lower TLR2 expression levels and interleukin-8 (IL-8) induction than in individuals with the TLR2 -196 to -174 ins/ins genotype (p < 0.05). Our data suggest the TLR2 -196 to -174 del allele to affect HCV viral loads and to increase the risk for HCC in HCV genotype1-infected patients.     

Associations of TNF-A-1031TT and -857TT genotypes with Helicobacter pylori seropositivity and gastric atrophy among Japanese Brazilians

Background Our previous study in a Japanese population showed elevated Helicobacter pylori seropositivity in those with tumor necrosis factor (TNF) A -1031TT and -857TT genotypes. This study examined the associations of this seropositivity and serum pepsinogen (PG) levels with these genotypes in Japanese Brazilians. Methods The subjects were 963 individuals (399 males and 564 females), aged 33 to 69 years, from four regions (Sao Paulo, Curitiba, Mogi das Cruzes, and Mirandopolis) in Brazil. Gastric atrophy was evaluated with serum pepsinogens (PGI < 70 ng/dl and PGI/II < 3), and TNF T-1031C and C-857T were genotyped by polymerase chain reaction with confronting two-pair primers (PCR-CTPP). Results The frequency of TNF-A T-1031C was 68.4% TT, 28.4% TC, and 3.3% CC, and that of C-857T was 64.5% CC, 31.7% CT, and 3.8% TT, whose distributions were in Hardy-Weinberg equilibrium. No significant associations of the genotypes with H. pylori seropositivity or gastric atrophy were found. However, male participants with TNF-A -1031CC and -857CC showed the lowest seropositivity (43.8% out of 16), and males with TNF-A -1031TT and -857TT showed the highest (61.5% out of 13). Conclusion This study demonstrated that the associations between H. pylori seropositivity and TNF-A genotypes were not marked for Japanese Brazilians. The genotypes were not associated with gastric atrophy among the seropositive individuals.     

Role of angiotensinogen gene polymorphism on Helicobacter pylori infection-related gastric cancer risk in Japanese

BACKGROUNDS AND AIMS: The renin-angiotensin (RA) system including angiotensinogen (AGT), angiotensin I and angiotensin II influences the regulation of cell proliferation, angiogenesis and inflammation. AGT-20 A/C polymorphism is associated with the plasma AGT and angiotensin II levels. The aim of this study was to clarify the association of AGT-20 A/C polymorphism with susceptibility to gastric cancer and peptic ulcer in Japanese. METHODS: We assessed the AGT-20 A/C polymorphism in Helicobacter pylori-positive patients with gastric cancer (n = 135), gastric ulcer (n = 148) and duodenal ulcer (n = 113) and controls (n = 292) consisting of H.pylori-positive gastritis alone (n = 160) and H.pylori-negative subjects (n = 132). RESULTS: The age- and sex-adjusted odds ratios (ORs) of AGT-20 A/C and C/C genotypes relative to A/A genotype for gastric cancer risk were 1.695 [95% confidence interval (CI): 1.035-2.777] and 2.259 (95% CI: 0.351-14.533), respectively. The AGT-20 C allele increased the gastric cancer risk (OR: 1.685, 95% CI: 1.037-2.736), especially the intestinal type of gastric cancer (OR: 1.792, 95% CI: 1.040-3.089). However, there was no association between the AGT-20 polymorphism and susceptibility to peptic ulcer. CONCLUSIONS: The carriage of AGT-20 C allele was associated with an increased risk for H.pylori-related gastric cancer development in Japanese, indicating that the RA system plays an important role in the pathogenesis of gastric cancer.     

Trends in the incidence of gastric cancer in Japan and their associations with Helicobacter pylori infection and gastric mucosal atrophy

Background Although age-adjusted mortality from gastric cancer has been decreasing in Japan, the crude incidence of gastric cancer shows a slight increase.Methods We have observed trends in the incidence of gastric cancer by sex and 20-year age groups over the past two decades (1976–1996). Source data were obtained from the cancer statistics materials provided by the Research Group for Population-Based Cancer Registration in Japan. Simultaneously, we observed changes in the prevalence of Helicobacter pylori infection and in serological atrophy of the gastric mucosa, and compared the results with those involving changes in the incidence of gastric cancer.Results A slight decline was observed in all age groups over 40 years old, in both men and women, between 1986 and 1996. However, a marked decline in incidence was observed for those aged 20–39 years. The prevalence of H. pylori infection declined in both sexes between 1989 and 1998. The frequency of serological atrophy of the gastric mucosa significantly declined in all age groups between 1989 and 1996, with young age groups experiencing a more marked decrease.Conclusion The marked decline in gastric cancer incidence observed in the young population will also begin to occur in the elderly population in the future.     

Lack of consistency in the associations of Helicobacter pylori seropositivity with Se and Le polymorphisms among Japanese

Background: In our previous study, a marked association between Helicobacter pylori seropositivity and functional polymorphisms of the secretor and Lewis genes (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.14–0.70 for se/se genotype relative to Se/Se genotype; and OR, 10.3; 95% CI, 3.16–33.8 for high-risk group defined by the combination of Se and Le relative to low-risk group) had been observed for 239 non-cancer Japanese outpatients of the gastroenterology clinic (OGC) undergoing gastroscopy at Aichi Cancer Center Hospital. Methods: The present study was a confirmatory study to examine the association for 679 first-visit outpatients (FVO) of all clinics at the same cancer hospital and for 465 health checkup examinees (HCE) in the same city. Results: The associations between H. pylori seropositivity and the Se and Le genotypes were nonsignificant or even in the opposite direction among the FVO (OR, 1.52; 95% CI, 1.00–2.32 for se/se genotype relative to Se/Se genotype; and OR, 0.77; 95% CI, 0.43–1.40 for the high-risk group defined similarly to the previous study), and among the HCE (OR, 1.25; 95% CI, 0.75–2.07; and OR, 1.07; 95% CI, 0.50–2.26, respectively). The discrepancy between the previous and present results was not explained by the difference in the distributions of age, sex, smoking, and H. pylori seroprevalence. Conclusion: Even in the same ethnic group, different sources of subjects may demonstrate inconsistent findings due to an unidentified effect modification. Inconsistent findings have rarely been reported by the same research group, but they are very important to understand the whole picture of the association under study. Received: May 9, 2002 / Accepted: July 2, 2002 Acknowledgments This work was supported in part by a Grant-in-Aid for the Second Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare of Japan. The authors are grateful to Ms. Naomi Takeuchi for genotyping. Offprint requests to: N. Hamajima     

Lack of consistency in the associations of Helicobacter pylori seropositivity with Se and Le polymorphisms among Japanese.

BACKGROUND: In our previous study, a marked association between Helicobacter pylori seropositivity and functional polymorphisms of the secretor and Lewis genes (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.14-0.70 for se/se genotype relative to Se/Se genotype; and OR, 10.3; 95% CI, 3.16-33.8 for high-risk group defined by the combination of Se and Le relative to low-risk group) had been observed for 239 non-cancer Japanese outpatients of the gastroenterology clinic (OGC) undergoing gastroscopy at Aichi Cancer Center Hospital. METHODS: The present study was a confirmatory study to examine the association for 679 first-visit outpatients (FVO) of all clinics at the same cancer hospital and for 465 health checkup examinees (HCE) in the same city. RESULTS: The associations between H. pylori seropositivity and the Se and Le genotypes were nonsignificant or even in the opposite direction among the FVO (OR, 1.52; 95% CI, 1.00-2.32 for se/se genotype relative to Se/Se genotype; and OR, 0.77; 95% CI, 0.43-1.40 for the high-risk group defined similarly to the previous study), and among the HCE (OR, 1.25; 95% CI, 0.75-2.07; and OR, 1.07; 95% CI, 0.50-2.26, respectively). The discrepancy between the previous and present results was not explained by the difference in the distributions of age, sex, smoking, and H. pylori seroprevalence. CONCLUSION: Even in the same ethnic group, different sources of subjects may demonstrate inconsistent findings due to an unidentified effect modification. Inconsistent findings have rarely been reported by the same research group, but they are very important to understand the whole picture of the association under study.     

Association between Toll-like receptor gene cluster (TLR6, TLR1, and TLR10) and prostate cancer.

BACKGROUND: Chronic inflammation may be a risk factor for prostate cancer. Previously, we found significant associations between single nucleotide polymorphisms (SNPs) and haplotypes in Toll-like receptor (TLR) 4 and the risk of prostate cancer. TLR6, TLR1, and TLR10 are also involved in the pathogen-mediated inflammation pathway. A Swedish study observed associations between sequence variants in the TLR6-TLR1-TLR10 gene cluster and the risk of prostate cancer. We assessed if genetic polymorphisms of this gene cluster were associated with the risk of prostate cancer in a U.S. population. METHODS: In a nested case-control design within the Health Professionals Follow-Up Study, we identified 700 participants with prostate cancer who were diagnosed after they had provided a blood specimen in 1993 and by January 31, 2000. Controls were 700 age-matched men without prostate cancer who had had a prostate-specific antigen test. We genotyped 19 common (>5%) haplotype-tagging SNPs chosen from the SNPs discovered in a resequencing study spanning TLR6, TLR1, and TLR10 to test for the association between sequence variants cluster and prostate cancer. RESULTS: Neither individual SNPs nor common haplotypes in the three gene regions were associated with altered risk of prostate cancer or subgroups of aggressive prostate cancer. No effect modification was observed for age, body mass index, or family history of prostate cancer, except that TLR6_3649 showed nominally significant interaction with family history at the P < 0.05 level. CONCLUSION: Inherited sequence variants of the innate immune gene cluster TLR6-TLR1-TLR10 were not appreciably associated with the risk of prostate cancer in this cohort.     

Interaction of cyclooxygenase-2 promoter polymorphisms with Helicobacter pylori infection and risk of gastric cancer

Overexpression of cyclooxygenase (COX)-2 has been implicated in the development of cancer. This study aimed to evaluate the relationship between genetic variants in COX-2 promoter interacting with Helicobacter pylori and the susceptibility to gastric cancer (GC). Three COX-2 polymorphisms -1290A>G (rs689465), -1195G>A (rs689466), and -765G>C (rs20417) were genotyped in 323 GC patients and 944 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression model. In GC patients, the ORs were 2.33 (95% CI = 1.50-3.63) and 2.70 (95% CI = 1.68-4.33) for -1195AA and -765CG genotype carriers, respectively. Haplotype analysis showed all -1195A allele-containing haplotypes, except G(-1290)-A(-1195)-G(-765), were associated with increased risk for GC, compared with the A(-1290)-G(-1195)-G(-765) haplotype. Moreover, significant multiplicative and additive interactions were observed between H. pylori infection and all these three polymorphisms, and H. pylori-infected subjects carrying the variant allele of -1290A>G, -1195G>A, or -765G>C had increased risk of GC compared with non-H. pylori-infected subjects with wild-type allele (OR = 4.10, 95% CI = 1.90-8.83; OR = 3.46, 95% CI = 1.31-9.11; and OR = 3.32, 95% = 1.27-8.73, respectively). Our results suggested that the COX-2 promoter polymorphisms were associated with increased risk of GC, especially interacting with H. pylori infection.     

Toll-like receptor 9 (TLR9) agonists in the treatment of cancer

Although still early in clinical development, agonists of Toll-like receptor 9 (TLR9) have demonstrated potential for the treatment of cancer. TLR9 agonists directly induce activation and maturation of plasmacytoid dendritic cells and enhance differentiation of B cells into antibody-secreting plasma cells. Preclinical and early clinical data support the use of TLR9 agonists in patients with solid tumors and hematologic malignancies. In preclinical studies, TLR9 agonists have shown activity not only as monotherapy, but also in combination with multiple other therapies, including vaccines, antibodies, cellular therapies, other immunotherapies, antiangiogenic agents, radiotherapy, cryotherapy and some chemotherapies. Phase I and II clinical trials have indicated that these agents have antitumor activity as single agents and enhance the development of antitumor T-cell responses when used as therapeutic vaccine adjuvants. The activity and safety of these novel anticancer agents are being explored in a wide range of tumor types as part of a variety of therapeutic strategies with the goal of harnessing the immune response to fight cancer.     

Helicobacter pylori,dietary factors,and atrophic gastritis in five Japanese populations with different gastric cancer mortality

In a cross-sectional study of 634 men aged 40 to 49 years, randomly selected from five areas of Japan with different rates of gastric cancer mortality, 121 men of 624 evaluated were diagnosed as having atrophic gastritis through serum pepsinogen I<70 ng/ml and the pepsinogen I (PGI)/pepsinogen II (PGII) ratio <3.0. We examined the relation of Helicobacter pylori (H. pylori) antibodies and dietary factors, including plasma level of antioxidant micronutrients, to the presence of atrophic gastritis. Presence of H. pylori IgG antibodies was associated with increased risk of atrophic gastritis (odds ratio [OR]=1.9, 95 percent confidence interval [CI]=1.1–3.3). As the level of plasma -carotene increased, we found a steady decrease in the risk of atrophic gastritis (OR for second quartile = 0.7, third quartile = 0.6, fourth quartile = 0.4, with CI=0.2–0.8). Frequent intake of yellow vegetables also was associated with lower risk, while frequent intake of soybean products was related to increased risk. Although H. pylori antibodies, -carotene level, and intake of soybean products were all significant in the multivariate analysis, these factors did not explain the differences in atrophic gastritis prevalence among the five regions. The analysis of these risk factors in relation to each pepsinogen marker showed that although both H. pylori infection and low plasma -carotene were associated with the decreased level of serum PGI/II ratio, the former was derived from the increase of PGII, which is common in early stage of atrophic gastritis, and the latter from the decrease of PGI, which is specific to severe atrophic gastritis. This finding suggests that H. pylori infection is associated with the formation of atrophic gastritis, while -carotene protects its advancement as well as formation.This study was supported in part by grants-in-aid for Cancer Research from the Ministry of Health and Welfare and for Scientific Research from the Ministry of Education, Science and Culture of Japan.     

miRNA-196a2 rs116149131基因多态性与胃癌患病风险的Meta分析

目的 探讨microRNA（miRNA）-196a2 rs116149131基因多态性与胃癌易感性的关系。方法 计算机检索PubMed、EMBASE、Cochrane library、中国知网、维普、万方及中国生物医学文献（CBD）等数据库中2016年3月1日之前关于miRNA-196a2 rs116149131基因多态性与胃癌易感性的相关研究。按纳入与排除标准筛选文献、提取资料并评价纳入研究的质量后,采用Stata 12.0软件进行Meta分析,计算合并OR值及其95％CI,并进行发表偏倚评估及敏感性分析。结果 共纳入9篇文献,包括3992例患者和5699例对照。Meta分析结果显示,miRNA-196a2 rs116149131基因多态性与胃癌易感性无明显相关性。按种族进行亚组分析结果显示,rs116149131基因多态性在杂合子模型中显著增加高加索人种胃癌患病风险（CT vs. TT：OR=1.93,95％CI：1.35～2.75,P＜0.05）;而在亚洲人种中未发现该位点多态性与胃癌易感性有关。根据对照组人群的来源进行亚组分析结果显示,在以医院和以人群为基础的研究中均未发现有与胃癌易感性相关的等位基因或者基因型。在T＜C亚组中,显性基因模型（CT+CC vs. TT：OR=1.40,95％CI：1.10～1.77,P=0.005）、纯合子模型（CC vs. TT：OR=1.59,95％CI：1.22～2.06,P=0.001）和杂合子模型（CT vs. TT：OR=1.33,95％CI：1.04～1.70,P=0.025）中发现rs116149131基因多态性与胃癌患病风险存在关联性;在等位基因模型和隐性基因模型中并未发现关联性。在T＞C组未发现rs116149131多态性与胃癌患病风险存在关联性。结论 miRNA-196a2 rs116149131基因多态性与胃癌患病风险无关联性,但存在种族差异。     

Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer

We conducted a longitudinal cohort study to determine the association of Helicobacter pylori infection and the progression of chronic atrophic gastritis (CAG) with gastric cancer. A cohort of 4655 healthy asymptomatic subjects was followed for a mean period of 7.7 years. H. pylori infection was established by serum specific antibodies and the presence of CAG was confirmed by serum pepsinogen. During the follow-up period, 45 gastric cancer cases were detected (incidence rate, 126/100000 person-years). A univariate analysis after adjustment for age showed that both H. pylori and CAG were significantly associated with gastric cancer. To clarify the interaction between H. pylori and CAG, an analysis stratified by H. pylori- and CAG-status was performed. No cancer developed in the H. pylori(-)/CAG(-) group during the study period. This supports the theory that it is quite rare for any type of gastric cancer to develop in an H. pylori-free healthy stomach. With the progression of H. pylori-induced gastritis, the risk of gastric cancer increased in a stepwise fashion from CAG-free gastritis [H. pylori(+)/CAG(-) group] (HR=7.13, 95%CI=0.95-53.33) to CAG [H. pylori(+)/CAG(+) group] (HR=14.85, 95%CI=1.96-107.7) and finally to severe CAG with extensive intestinal metaplasia [H. pylori(-)/CAG(+) group] (HR=61.85, 95%CI=5.6-682.64) in which loss of H. pylori from the stomach is observed. Therefore, it is probable that H. pylori alone is not directly associated with stomach carcinogenesis. Instead, H. pylori appears to influence stomach carcinogenesis through the development of CAG. The observed positive correlation between the extent of H. pylori-induced gastritis and the development of cancer was strong, especially for the intestinal type. These results are compelling evidence that severe gastritis with extensive intestinal metaplasia is a major risk factor for gastric cancer, and they confirm the previously described model of stomach carcinogenesis: the gastritis-metaplasia-carcinoma sequence.     

Salt intake and gastric cancer risk according to Helicobacter pylori infection, smoking, tumour site and histological type

Background:

Although salt intake is considered a probable risk factor for gastric cancer, relevant studies have provided heterogeneous results, and the magnitude of the association has not been accurately quantified.

Methods:

To quantify gastric cancer risk in relation to dietary salt exposure according to Helicobacter pylori infection status and virulence, smoking, tumour site, and histological type, we evaluated 422 gastric cancer cases and 649 community controls. Salt exposure was estimated in the year before the onset of symptoms through: sodium intake (estimated by a food frequency questionnaire (FFQ)); main food items/groups contributing to dietary sodium intake; visual analogical scale for salt intake preference; use of table salt; and duration of refrigerator ownership.

Results:

Comparing subjects with the highest with those with the lowest salt exposure (3rd vs 1st third), sodium intake (OR=2.01, 95% CI: 1.16–3.46), consumption of food items with high contribution to sodium intake (OR=2.54, 95% CI: 1.56–4.14) and salt intake evaluated by visual analogical scale (OR=1.83, 95% CI: 1.28–2.63) were associated with an increased gastric cancer risk. Subjects owning a refrigerator for >50 years had a lower risk for gastric cancer (OR=0.28, 95% CI: 0.14–0.57). These associations were observed regardless of H. pylori infection status and virulence, smoking, tumour site or histological type.

Conclusion:

Our results support the view that salt intake is an important dietary risk factor for gastric cancer, and confirms the evidence of no differences in risk according to H. pylori infection and virulence, smoking, tumour site and histological type.     

Genetic polymorphism of cytochrome P450 (CYP) 1A1, CYP1A2, and CYP2E1 genes modulate susceptibility to gastric cancer in patients with Helicobacter pylori infection

Background

Activity of cytochrome P450 (CYP), a polymorphic carcinogen-activating enzyme, is exaggerated following Helicobacter pylori infection. We studied the role of CYP2E1, CYP1A2 (rs762551), and CYP1A1 (rs4646903) polymorphisms in association with H. pylori infection in gastric carcinogenesis.

Methods

Genotyping of CYP2E1 (96-bp insertion), CYP1A2 (164A to C), and CYP1A1 (3801C to T) was carried out in 88, 76, 53, and 170 patients with gastric cancer (GC), functional dyspepsia (FD), peptic ulcer (PU), and healthy controls (HC), respectively. Serum IgG antibody (all subjects), rapid urease test, and histology (GC, FD, and PU patients) were used to test for H. pylori.

Results

CYP2E1 gene polymorphism was more common among patients with GC than HC and PU [48/88 (54.5 %) vs. 67/170 (39.4 %); OR 1.9, 95 % CI 1.1–3.2, p = 0.016) and [PU 18/53 (34 %); OR 2.3 (1–4.7), p = 0.02]. CYP1A2 CC or CT genotypes was lower among patients with GC than HC [50/88 (56.8 %) vs. 120/170 (70.6 %); OR 0.54 (0.31–0.92), p = 0.023]. CYP1A1 polymorphism and CYP1A1–CYP1A2 haplotypes were comparable among different groups. CYP2E1 was also more common in patients with GC than HC and PU in the absence of H. pylori [33/60 (55 %) vs. 19/52 (36.5 %); OR 4 (1.5–11.4), p = 0.007 and PU 7/22 (31.8 %); OR 3.4 (1–11.6), p = 0.05]. CYP1A1 (CT + TT) was more common in patients with GC than PU in presence of H. pylori [17/26 (65.4 %) vs. 11/29 (38 %); OR 3.0 (1.03–9.3), p = 0.045].

Conclusions

The presence of CYP2E1 (96-bp insertion) is associated with increased risk of GC even in absence of H. pylori. CYP1A2 CC or CT is associated with reduced risk of GC.     

Morphologic criteria using biopsy specimens to define the risk of gastric cancer in patients with Helicobacter pylori infection

Although Helicobacter pylori (H. pylori) infection is associated with gastric cancer most patients infected with H. pylori do not develop gastric cancer. Gastric biopsy specimens were taken from 49 patients with early intestinal-type gastric cancer and from 49 age- and sex-matched control subjects. Histological features of gastritis were graded according to the updated Sydney System. Mononuclear cell infiltration of the corpus, and intestinal metaplasia of the angle increased the risk of developing gastric cancer. Probability of gastric cancer (PCA) was calculated using these two parameters. The specificities of 70 < PCA for gastric cancer patients, and PCA < 30 for non-cancer subjects were 94 and 95%, respectively. PCA < 20 was observed only in control subjects. Calculation of PCA, which requires only two biopsy specimens, may be useful to define the patients at high or low risk of intestinal-type gastric cancer among patients infected with H. pylori.