A prospective study of dietary salt intake and gastric cancer incidence in a defined Japanese population: the Hisayama study

The results of prospective studies of the association between dietary salt intake and gastric cancer occurrence remain controversial. To examine this issue in a cohort study of a general population, 2,476 subjects aged 40 years or older were stratified into 4 groups according to the amount of daily salt intake: namely, <10.0, 10.0-12.9, 13.0-15.9, and > or = 16.0 per day and were followed up prospectively for 14 years. During the follow-up period, 93 subjects developed gastric cancer. The age- and sex-adjusted incidence was significantly higher in the second to fourth groups than in the first group (age- and sex-adjusted hazard ratio [95% confidence interval], 2.42 [1.24-4.71] for the second group; 2.10 [1.03-4.30] for the third group; 2.98 [1.53-5.82] for the fourth group). This association remained substantially unchanged even after adjusting for other confounding factors such as age, sex, Helicobacter pylori infection, atrophic gastritis, medical history of peptic ulcer, family history of cancer, body mass index, diabetes, total cholesterol, physical activity, alcohol intake, smoking habit and other dietary factors. In the stratified analysis, a significant salt-cancer association was observed only in subjects who had both Helicobacter pylori infection and atrophic gastritis (age- and sex-adjusted hazard ratio, 2.87 [1.14-7.24]). Our findings suggest that high dietary salt intake is a significant risk factor for gastric cancer; moreover, this association was found to be strong in the presence of Helicobacter pylori infection with atrophic gastritis.     

NFKBIA基因多态性、饮食习惯及其交互作用与胃癌易感性的关系

目的：分析NFKBIA基因多态性、饮食习惯及其交互作用与胃癌易感性的关系。方法：采用1∶1配对病例对照研究设计，收集2013年4月—2017年6月福建仙游县医院587例胃癌新发病例和按性别、年龄匹配的587例健康人群为研究对象，采用自制调查表收集一般情况、饮食习惯等资料，利用Sequenom MassARRAY SNP方法检测外周血NFKBIA基因rs696位点的基因型。应用条件logistic回归模型分析饮食习惯、基因型对胃癌发病风险的影响，利用叉生分析结合logistic回归模型和Andersson等编制的Excel表进行基因与环境的交互作用分析。结果：快速饮食、不规律进餐、高盐饮食和经常摄入腌菜是胃癌发生的危险因素，OR（95% CI）分别为1.53（1.20，1.95）、1.55（1.16，2.08）、1.51（1.17，1.94）、2.78（2.01，3.85）；NFKBIA基因rs696位点携带AG基因型、AA基因型、显性模型（AG+AA）增加胃贲门癌发病风险。此外，rs696位点AA基因型与高盐饮食、经常摄入腌菜存在联合作用，rs696位点显性模型（AG+AA）与快速饮食、高盐饮食、经常摄入腌菜存在联合作用，均增加胃贲门癌发病风险。结论：不良饮食习惯是胃癌发生的危险因素，NFKBIA基因rs696位点AA基因型、显性模型（AG+AA）增加胃贲门癌发病风险，且与饮食习惯存在联合作用。     

Helicobacter pylori,gastric microbiota and gastric cancer relationship: Unrolling the tangle

Helicobacter pylori infection (Hp-I) represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related factors, leading to inflammatory changes, dysbiosis and eventually gastric cancer. The normal gastric microbiota shows diversity, with Proteobacteria [Helicobacter pylori (H. pylori) belongs to this family], Firmicutes, Actinobacteria, Bacteroides and Fusobacteria being the most abundant phyla. Most studies indicate that H. pylori has inhibitory effects on the colonization of other bacteria, harboring a lower diversity of them in the stomach. When comparing the healthy with the diseased stomach, there is a change in the composition of the gastric microbiome with increasing abundance of H. pylori (where present) in the gastritis stage, while as the gastric carcinogenesis cascade progresses to gastric cancer, the oral and intestinal-type pathogenic microbial strains predominate. Hp-I creates a premalignant environment of atrophy and intestinal metaplasia and the subsequent alteration in gastric microbiota seems to play a crucial role in gastric tumorigenesis itself. Successful H. pylori eradication is suggested to restore gastric microbiota, at least in primary stages. It is more than clear that Hp-I, gastric microbiota and gastric cancer constitute a challenging tangle and the strong interaction between them makes it difficult to unroll. Future studies are considered of crucial importance to test the complex interaction on the modulation of the gastric microbiota by H. pylori as well as on the relationships between the gastric microbiota and gastric carcinogenesis.     

NFKBIA基因多态性、饮食习惯及其交互作用与胃癌易感性的关系

目的:分析NFKBIA基因多态性、饮食习惯及其交互作用与胃癌易感性的关系。方法:采用1∶1配对病例对照研究设计,收集2013年4月-2017年6月福建仙游县医院587例胃癌新发病例和按性别、年龄匹配的587例健康人群为研究对象,采用自制调查表收集一般情况、饮食习惯等资料,利用Sequenom Mass ARRAY SNP方法检测外周血NFKBIA基因rs696位点的基因型。应用条件logistic回归模型分析饮食习惯、基因型对胃癌发病风险的影响,利用叉生分析结合logistic回归模型和Andersson等编制的Excel表进行基因与环境的交互作用分析。结果:快速饮食、不规律进餐、高盐饮食和经常摄入腌菜是胃癌发生的危险因素,OR(95%CI)分别为1.53(1.20,1.95)、1.55(1.16,2.08)、1.51(1.17,1.94)、2.78(2.01,3.85);NFKBIA基因rs696位点携带AG基因型、AA基因型、显性模型(AG+AA)增加胃贲门癌发病风险。此外,rs696位点AA基因型与高盐饮食、经常摄入腌菜存在联合作用,rs696位点显性模型(AG+AA)与快速饮食、高盐饮食、经常摄入腌菜存在联合作用,均增加胃贲门癌发病风险。结论:不良饮食习惯是胃癌发生的危险因素,NFKBIA基因rs696位点AA基因型、显性模型(AG+AA)增加胃贲门癌发病风险,且与饮食习惯存在联合作用。     

Evaluation of polygenic risk score for risk prediction of gastric cancer

Genetic variations are associated with individual susceptibility to gastric cancer.Recently, polygenic risk score(PRS) models have been established based on genetic variants to predict the risk of gastric cancer. To assess the accuracy of current PRS models in the risk prediction, a systematic review was conducted. A total of eight eligible studies consisted of 544842 participants were included for evaluation of the performance of PRS models. The overall accuracy was moderate with Area under the...     

幽门螺杆菌感染与胃癌及癌前病变中P21蛋白的表达

 用LSAB免疫组化法，对20例谓癌、22例异型增生、30例肠化生及13例正常组织进行了P21蛋白表达的检测。结果发现，胃癌、异型增生和肠化生的P21阳性者分别为13例（65.0%）,12例（60.0%）,11例（36.6%）,正常组织全部阴性；三种组织中，HP阳性病人的P21阳性率为41.6%（30/72）,明显高于HP阴性病人的8.3%（6/72）,有显着差别（P<0.01）.说明HP感染与P21过度表达存在着明显的相关性。提示HP感染可能通过ras癌基因的突变而参予致癌作用。     

Methylenetetrahydrofolate Reductase Genotypes, Dietary Habits and Susceptibility to Stomach Cancer

OBJECTIVE To study the relation among methylenetetrahydrofolate reductase (MTHFR) C677T genotypes, dietary habits and the risk of stomach cancer (SC).METHODS A case-control study was conducted with 107 cases of SC and 200 population-based controls in Chuzhou district, Huaian, Jiangsu province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects..MTHFR genotypes were detected by PCR-RFLP. RESULTS (1) The prevalence of the MTHFR C/T or T/T genotypes was found to be significantly different between controls (68.5%) and SC cases (79.4%,P=0.0416), the increased risk had an adjusted OR of 1.79 (95?:1.01-3.19). (2) Among subjects who had a low intake of garlic or Chinese onion, MTHFR C/T or T/T genotypes significantly increased the risk of developing SC. Among non-tea drinkers or among subjects who had a frequent intakeof meat, the carriers of the MTHFR C/T or T/T genotypes had a higher risk of SC than individuals with the C/C type MTHFR. CONCLUSION The polymorphism of MTHFR C677T was associated with increased risk of developing SC, and that individuals with differing genotypes may have different susceptibilities to SC, based on their exposure level to environmental factors.     

Methylenetetrahydrofolate reductase genotypes, dietary habits and susceptibility to stomach cancer

Objective To study the relation among methylenetetrahydrofolate reductase (MTHFR) C677T genotypes, dietary habits and the risk of stomach cancer (SC). Methods A case-control study was conducted with 107 cases of SC and 200 population -based controls in Chuzhou district, Huaian. Jiangsu province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects, MTHFR genotypes were detected by PCR-RFLP. Results (1) The prevalence of the MTHFR C/T or T/T genotypes was found to be significantly different between controls (68.5%) and SC cases (79.4%. P =0.0416), the increased risk had an adjusted OR of 1.79 (95%CI: 1.01 -3.19). (2) Among subjects who had a low intake of garlic or Chinese onion, MTHFR C/T or T/T genotypes significantly increased the risk of developing SC. Among non-tea drinkers or among subjects who had a frequent intake of meat, the carriers of the MTHFR C/T or T/T genotypes had a higher risk of SC than individuals with the C/C type MTHFR. Conclusion The polymorphism of MTHFR C677T was associated with increased risk of developing SC, and that individuals with differing genotypes may have different susceptibilities to SC, based on their exposure level to environmental factors. This work was supported in part by a Grant-in Aid for International Scientific Research, Special Cancer Research (No.08042015, 11137311) from the Ministry of Education, Science, Sports, Culture and Technology, Japan.     

Early-onset gastric cancer: Learning lessons from the young

There is by no means a clear-cut pattern of mutations contributing to gastric cancers, and gastric cancer research can be hampered by the diversity of factors that can induce gastric cancer, such as Helicobacter pylori infection, diet, ageing and other environmental factors. Tumours are unquestionably riddled with genetic changes yet we are faced with an unsolvable puzzle with respect to a temporal relationship. It is postulated that inherited genetic factors may be more important in early-onset gastric cancer (EOGC) than in gastric cancers found in older patients as they have less exposure to environmental carcinogens. EOGC, therefore, could provide a key to unravelling the genetic changes in gastric carcinogenesis. Gastric cancers occurring in young patients provide an ideal background on which to try and uncover the initiating stages of gastric carcinogenesis. This review summarizes the literature regarding EOGC and also presents evidence that these cancers have a unique molecular-genetic phenotype, distinct from conventional gastric cancer.     

Dietary habits and mammographic patterns in patients with breast cancer

Summary Between 1983 and 1986, dietary history interviews were conducted with 238 women aged 50–65 years who had surgery for stage I–II breast cancer. Diagnostic mammograms were coded in line with Wolfe's criteria in N1, P1, P2, and Dy patterns. Women with Dy pattern reported significantly higher intake of total fat, monounsaturated fatty acids (FA), polyunsaturated FA, n-3 FA, n-6 FA in per cent of energy (E%), and -tocopherol in mg/10 MJ. Fat intake was lowest in women with N1 pattern and highest in those having Dy pattern. Patients having ER-rich cancers and Dy pattern reported significantly higher intake of total fat, monounsaturated FA, polyunsaturated FA, n-6 FA (E%), and -tocopherol (mg/10 MJ), as well as significantly lower intake of carbohydrate (E%) and calcium (g/10 MJ). In the stepwise multivariate analysis, the multivariate-odds ratio (OR) for having P2 + Dy patterns was 1.06 (95% confidence interval (CI), 1.02–1.12) for each increment in E% of total fat. In women with ER-rich tumors this OR was 1.09 (95% CI, 1.02–1.16). The highest self-reported body mass index (BMI) was observed in women with N1 + P1 patterns. OR for having P2 + Dy patterns was 0.91 (95% CI, 0.83–0.98) for each increment in 1 kg/m² of BMI. The results suggest that dietary habits affect the mammographic parenchymal pattern in women with breast cancer and that a high fat intake is associated with a higher proportion of mammograms with Dy pattern in such patients.     

胃癌与肿瘤微环境的研究进展

胃癌（Gastriccarcinoma,GC）的发病率居全世界恶性肿瘤的第四位,死亡率居第二位。尽管胃癌的发病率在过去的几十年里有所下降,但它仍然是一个严重危害健康的问题。肿瘤微环境在肿瘤的发生和进展中有重要作用,主要包括肿瘤相关的巨噬细胞、淋巴细胞、癌相关成纤维细胞、血管生成因子、细胞因子、肿瘤微环境以及它们作用机制的信号趋化因子等。本文就肿瘤微环境与胃癌相关性的研究进展综述如下。     

Prevalence of Helicobacter pylori infection in gastric remnant after distal gastrectomy for primary gastric cancer

Background. The development of a second primary cancer in the gastric remnant after gastrectomy for early gastric carcinoma is a problem, and eradication of Helicobacter pylori after the operation has been recommended. However, to date, practical indications for H. pylori eradication after gastric cancer surgery have not yet been reported. Methods. We examined H. pylori infection in the gastric remnant after distal gastrectomy for primary gastric cancer. One hundred and nine patients who had had a gastrectomy were studied. Endoscopic findings and results from the urease test, bacteriologic assessment, serological test, and histopathological examination were analyzed. Results. Seventy-one patients (65.1%) were judged to be positive for H. pylori infection. The prevalence of H. pylori infection was found to be significantly decreased in older patients, patients in whom the operation had been performed a long time before examination, patients with symptoms, and patients with severe reflux gastritis. On the other hand, histologically, chronic and acute gastritis correlated significantly with H. pylori infection. H. pylori prevalence was highest in mildly atrophic mucosa and decreased with more extensive atrophic changes of the mucosa. Conclusions. The persistence of H. pylori -related active gastritis in the gastric remnant after gastric cancer surgery was suggested in younger patients with mild atrophic gastritis and without reflux gastritis. These patients may be the best candidates for H. pylori eradication therapy. Received: April 13, 2001 / Accepted: June 18, 2001     

Factors affecting survival in operated gastric cancer

In this study, our aim was to determine the possible effects of Helicobacter pylori (HP), chronic atrophic gastritis (CAG), and gastrointestinal metaplasia (GIM) on survival in operated bowel type gastric cancer patients (INT-GC). Among 548 patients, 347(63.3%) were male. The median age was 57 years. Disease-free survival (DFS) and overall survival (OS) were significantly shorter in patients with GIM than those in patients without GIM (log rank, P = 0.003 and log rank P = 0.003, respectively). Multivariate analysis showed that presence of GIM (HR, 2.1) was found to be an independent factor of worse DFS. In our study, stage pIII patients with GIM had significantly shorter DFS and OS than those without GIM (log rank p = 0.008 and log rank p = 0.001, respectively). However, in subgroup analysis of patients with GIM, there was no significant DFS and OS difference between patients with stage pI and pII disease (log rank p = 0.999, log rank p = 0.184 vs. log rank p = 0.409, log rank p = 0.281, respectively).     

Dietary patterns and risk of gastric cancer: a case-control study in Uruguay

Background Gastric cancer is a frequent malignancy in the Uruguayan population. In northern counties, incidence rates reach high figures (age-standardized rates [ASR], 37.3 per 100000 men and 18.3 per 100000 women). Diet is a major determinant in gastric carcinogenesis. Because foods or food groups have the advantage over nutrients in being most directly related to dietary recommendations, we decided to conduct a case-control study on the relationships between food groups and risk of gastric cancer. For this purpose, we included 240 cases and 960 controls.Methods In the present study we employed three analytical approaches: (1) individual food group analysis, (2) factor analysis, and (3) analysis of empirical scores of risk. Individual analysis of food groups was performed by multiple unconditional logistic regression, with food groups being the explanatory variables. Nineteen food groups were created and categorized in tertiles according to the control distribution. Factor analysis aggregated intercorrelated foods in broader eating patterns. In this study we were able to identify three factors or patterns, arbitrarily labeled starchy, healthy, and mixed. Finally, empirical scores of risk were created after examining the risk of each individual food and summing each significant item. This resulted in a risk enhancing score and a protective score. Both scores were categorized in tertiles according to the control distribution.Results The individual analysis of food groups showed increased risks of gastric cancer for rice, salted meat, stewed meat, white bread, potatoes, and tubers. On the other hand, raw vegetables, total fruits, legumes, and black tea were inversely associated with risk of gastric cancer. All three dietary patterns, generated by factor analysis, were significantly associated with gastric carcinoma risk. Whereas the starchy factor was directly associated with gastric cancer, the healthy and mixed patterns were strongly protective. Finally, the risk enhancing empirical score displayed an increased risk of gastric cancer (odds ratio [OR], 4.1, 95% confidence interval [CI], 2.6–6.6), whereas the protective score showed an important reduction in risk, of 0.38.Conclusion This study displayed consistent results from three different approaches. Concerning different food groups, stewed and processed meat are rich in salt; rice, tubers, and winter squash are sources of starch; and vegetables and fruits are rich in ascorbic acid and carotenoids. All these substances have been strongly related to gastric carcinogenesis. Furthermore, this study suggests that diets rich in vegetables and fruits and with low amounts of salty and starchy foods are recommendable for the prevention of gastric cancer.     

Role of interleukin polymorphisms in gastric cancer: "Pros and cons"

Helicobacter pylori (H. pylori) infection is the leading cause of gastric cancer worldwide. Infection with this bacterium causes a chronic active immune response that persists for the life of the host. The combination of bacterial factors, environmental insults, and the host immune response drives the initiation and progression of mucosal atrophy, metaplasia, and dysplasia toward GC. Among the host factors, IL-1 gene cluster polymorphisms (IL-1B encoding IL-1β and IL-1RN encoding IL-1ra, its naturally occurring receptor antagonist) play a decisive role in modulating the risk of developing hypochlorhydria, gastric atrophy and GC in the presence of H. pylori infection. In particular, one single nucleotide polymorphism in the IL-1B promoter (IL-1B-511C⁄T), and the short allele of a 86-bp variable number of tandem repeats polymorphism in the IL-1RN second intron (IL-1RN*2) are associated with an increased risk for GC. However this hypothesis is still to be fully confirmed. This review focuses on the divergent results obtained by several epidemiological and functional in vitro and in vivo studies and show that IL-1 genotyping has still no role in the clinical management of patients with H. pylori infection.     

Screening for gastric cancer in China: Advances,challenges and visions

Gastric cancer (GC) is one of the major cancers in China and all over the world. Most GCs are diagnosed at an advanced stage with unfavorable prognosis. Along with some other countries, China has developed the government-funded national screening programs for GC and other major cancers. GC screening has been shown to effectively decrease the incidence of and mortality from GC in countries adopting nationwide screening programs (Japan and Korea) and in studies based on selected Chinese populations. The screening of GC relies mostly on gastroendoscopy, the accuracy, reliability and safety of which have been indicated by previous studies. However, considering its invasive screening approach, requirements on skilled endoscopists and pathologists, and a high cost, developing noninvasive methods to amend endoscopic screening would be highly needed. Numerous studies have examined biomarkers for GC screening and the combination of biomarkers involving pepsinogen, gastrin, and Helicobacter pylori antibodies has been proposed for risk stratification, seeking to narrow down the high-risk populations for further endoscopy. Despite all the achievements of endoscopic screening, evidence on appropriate screening age, intervals for repeated screening, novel biomarkers promoting precision prevention, and health economics need to be accumulated to inform policymakers on endoscopic screening in China. With the guide of Health China 2030 Planning Outline, we have golden opportunities to promote prevention and control of GC. In this review, we summarize the characteristics of screening programs in China and other East Asian countries and introduce the past and current approaches and strategies for GC screening, aiming for featuring the latest advances and key challenges, and illustrating future visions of GC screening.     

Adult dietary intake and prostate cancer risk in Utah: a case-control study with special emphasis on aggressive tumors

A population-based case-control study in Utah of 358 cases diagnosed with prostate cancer between 1984 and 1985, and 679 controls categorically matched by age and county of residence, were interviewed to investigate the association between dietary intake of energy (kcal), fat, protein, vitamin A, beta-carotene, vitamin C, zinc, cadmium, selenium, and prostate cancer. Dietary data were ascertained using a quantitative food-frequency questionnaire. Data were analyzed separately by age (45-67, 68-74) and by tumor aggressiveness. The most significant associations were seen for older males and aggressive tumors. Dietary fat was the strongest risk factor for these males, with an odds ratio (OR) of 2.9 (95 percent confidence interval [CI] 1.0-8.4) for total fat; OR = 2.2 (CI = 0.7-6.6) for saturated fat; OR = 3.6 (CI = 1.3-9.7) for monounsaturated fat; and OR = 2.7 (CI = 1.1-6.8) for polyunsaturated fat. Protein and carbohydrates had positive but nonsignificant associations. Energy intake had an OR of 2.5 (CI = 1.0-6.5). In these older men, no effects were seen for dietary cholesterol, body mass, or physical activity. There was little association between prostate cancer and dietary intake of zinc, cadmium, selenium, vitamin C, and beta-carotene. Total vitamin A had a slight positive association with all prostate cancer (OR = 1.6, CI = 0.9-2.4), but not with aggressive tumors. No associations were found in younger males, with the exception of physical activity which showed active males to be at an increased but nonsignificant risk for aggressive tumors (OR = 2.0, CI = 0.8-5.2) and beta-carotene which showed a nonsignificant protective effect (OR = 0.6, CI = 0.3-1.6). The findings suggest that dietary intake, especially fats, may increase risk of aggressive prostate tumors in older males.