Risk Of Gastric Cardia Adenocarcinoma Research Articles

Cereal fiber intake may reduce risk of gastric adenocarcinomas: The EPIC‐EURGAST study

Numerous case-control studies suggest dietary fiber may reduce risk of gastric cancer, but this has not been confirmed prospectively. A previous case-control study reported reduced risk of gastric cardia adenocarcinomas associated with cereal fiber, but not with fruit or vegetable fiber. To date, different food sources of fiber have not been examined with respect to noncardia tumors or diverse histologic sub-types. This study prospectively examines associations between fiber from different food sources and incident gastric adenocarcinomas (GC) among more than 435,000 subjects from 10 countries participating in the European Prospective Investigation into Cancer and Nutrition study. Subjects aged 25-70 years completed dietary questionnaires in 1992-98, and were followed up for a median of 6.7 years. About 312 incident GCs were observed. The relative risk of GC was estimated based on cohort-wide sex-specific fiber intake quartiles using proportional hazards models to estimate hazards ratios (HRs) and 95% confidence intervals (CIs). Intakes of cereal fiber, but not total, fruit or vegetable fiber, were associated with reduced GC risk [adjusted HR for the highest vs. lowest quartile of cereal fiber 0.69, 0.48-0.99]. There was a strong inverse association for diffuse [HR 0.43, 0.22-0.86], but not intestinal type [HR 0.98, 0.54-1.80] tumors. Associations for cardia vs. noncardia tumors were similar to those for overall GC, although cardia associations did not reach significance. Cereal fiber consumption may help to reduce risk of GC, particularly diffuse type tumors. Further study on different food sources of fiber in relation to GC risk is warranted to confirm these relationships.

Association of MTHFR C677T and SHMT1 C1420T with susceptibility to ESCC and GCA in a high incident region of Northern China

To assess the association between the C to T transition in the methylenetetrahydro folate reductase gene (MTHFR C677T) and the C to T transition in the serine hydroxymethyltransferase ( 1 )gene (SHMT ( 1 ) C1420T) and the increased risk of carcinogenesis of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in a population of high incident region of Northern China. The polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism and PCR-confronting two-pair primers analysis respectively among 1051 cancer patients (584 ESCC and 467 GCA) and 540 healthy controls. The MTHFR 677T/T genotype significantly increased susceptibility to both ESCC and GCA compared with the C/C genotype, the adjusted OR was 2.13 (95% CI = 1.50-3.02) and 1.28 (95% CI = 1.07-1.53, respectively. For the SHMT ( 1 ) C1420T polymorphism, the C/C genotype was significantly associated with the increased risk of ESCC and GCA, compared with the C/T genotype (the adjusted OR = 1.43 and 1.35, 95% CI = 1.02-2.00 and 1.11-1.63, respectively). The interactive influence of the MTHFR and SHMT ( 1 ) polymorphisms in the risk of ESCC and GCA was also observed. The association between the MTHFR C677T and SHMT ( 1 ) C1420T polymorphisms and the risk of ESCC and GCA was demonstrated.

Dietary Patterns and Risk of Squamous-Cell Carcinoma and Adenocarcinoma of the Esophagus and Adenocarcinoma of the Gastric Cardia: A Population-Based Case-Control Study in Sweden

: We conducted a large population-based case-control study in Sweden to examine the association of dietary patterns and the development of cancers from the esophagus or gastroesophageal junction. In total 185 patients with esophageal adenocarcinoma, 165 with esophageal squamous-cell carcinoma, 258 with gastric cardia adenocarcinoma, and 815 randomly selected population controls underwent face-to-face interviews. Exploratory factor analysis was used to identify possible dietary patterns. Multivariate logistic regression with adjustments for age, sex, years of education, body mass index, physical activity, symptomatic gastroesophageal reflux, smoking, and total energy intake was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs). We identified three major dietary patterns in this population, for example, "healthy diet" (high in vegetables, tomato, fruits, fish, and poultry), "Western diet" (high in processed meat, red meat, sweets, high-fat dairy, and high-fat gravy), and "alcohol drinker" (high in intakes of beer, liquor, and French fries). We found that a healthy diet tended to moderately decrease the risk of all three cancers under study, although none of the associations was statistically significant. A high score of Western diet was associated with increased risks of gastric cardia adenocarcinoma (high 3rd tertile vs. low 1st quartile, OR = 1.8, 95% CI = 1.1-2.9, P for trend = 0.04) and esophageal adenocarcinoma (high 3rd tertile vs. low 1st tertile, OR = 1.6, 95% CI = 0.9-3.1, P for trend = 0.13), whereas a dietary pattern characterized by high beer and liquor intake (alcohol drinker) significantly increased the risk of squamous-cell carcinoma of the esophagus (3rd tertile vs. low 1st tertile, OR = 3.5, 95% CI = 1.9-6.3, P for trend < 0.0001). Our study confirms the important role of diet in the carcinogenesis of esophageal and cardia cancer.

Significant increase in risk of gastroesophageal cancer is associated with interaction between promoter polymorphisms in thymidylate synthase and serum folate status

Thymidylate synthase (TS) catalyzes the 5,10-methylene-tetrahydrofolate-mediated conversion of deoxyuridine monophosphate to deoxythymydine monophosphate, a nucleotide required for DNA synthesis and repair. The impaired TS expression has been shown to be related to 28 bp tandem repeats and a G-->C SNP in the 5'-UTR of TS. Folate deficiency has been demonstrated to play a role in gastroesophageal carcinogenesis. This case-control study was to examine the hypothesis that the TS polymorphisms, alone or in combination with serum folate status, may confer susceptibility of the hosts to gastroesophageal cancer. We analyzed TS genotype and serum folate concentration in 324 patients with esophageal squamous cell carcinoma (ESCC), 231 patients with gastric cardia adenocarcinoma (GCA) and 492 controls. It was found that compared with the normal expression TS genotype, the low expression TS genotype alone was significantly associated with increased risk of ESCC [adjusted odds ratio (OR) 1.47; 95% confidence interval (CI) 1.03-2.10] but not GCA (OR=0.98, 95% CI=0.68-1.40). More importantly, a significant interaction between the TS polymorphisms and serum folate status in risk of ESCC and GCA was observed. Among subjects with low serum folate concentration (<3 ng/ml), the ORs of ESCC and GCA for the low expression genotype were 22.63 (95% CI=10.44-49.05) and 4.08 (95% CI=1.94-8.59), which were greater than respective 9.97 (95% CI=5.67-17.53) and 1.88 (95% CI=1.18-3.24) for the normal expression genotype (P=0.002 and 0.029). These results suggest an important role for folate deficiency and impaired TS activity in the etiology of ESCC and GCA.

Methylenetetrahydrofolate reductase polymorphisms/haplotypes and risk of gastric cancer: a case-control analysis in China.

Studies have suggested that low dietary folate intake is associated with an increased risk of gastric cancer. Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and influences DNA methylation and nucleotide synthesis. MTHFR is highly polymorphic and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level. We hypothesized that three MTHFR common variants (i.e. C677T, A1298C and G1793A) and their haplotypes are associated with the risk of gastric cancer. To test this hypothesis, we genotyped these polymorphisms in a population-based case-control study of 320 incident gastric adenocarcinoma cases and 313 cancer-free controls in a Chinese population. Consistent with our previous observations, the 677TT genotype was associated with a significantly increased risk for gastric cancer (adjusted OR =1.79, 95% CI =1.02-3.15) compared with the 677CC genotype; the association was more evident for gastric cardia adenocarcinoma (adjusted OR =2.60, 95% CI =1.30-5.21). When we used the haplotype analyses and assumed MTHFR 677T, 1298C and 1793A as risk alleles, individuals with 6 variant alleles had a significantly (4.64-fold) increased risk for gastric cardia adenocarcinoma (OR =4.64, 95% CI =1.34-16.01) compared with those having 0-2 variants. These findings suggest that the MTHFR common variants and their haplotypes may play a role in the etiology of gastric cancer, particularly gastric cardia adenocarcinoma. Future studies using large sample sizes and incorporating detailed data on dietary folate intake and related serological measurements are warranted to confirm our findings.

Variants of the IL8 and IL8RB Genes and Risk for Gastric Cardia Adenocarcinoma and Esophageal Squamous Cell Carcinoma

Abstract The population of Linxian in north central China is at high risk for gastric cardia adenocarcinoma (GCC) and esophageal squamous cell carcinoma (ESCC), and chronic inflammation may contribute to this risk. Interleukin-8 (IL8), a potent chemoattractant, has three well-characterized single nucleotide polymorphisms (SNP), one (−251) of which alters transcriptional activity. Four well-described SNPs in the two IL8 receptors, IL8RA and IL8RB, have been associated with inflammation. We conducted a case-cohort study in the Nutrition Intervention Trials (Linxian, China) to assess the association between these SNPs and incident GCC (n = 90) and ESCC (n = 131). IL8, IL8RA, and IL8RB SNPs were analyzed using a multiplex assay system, haplotypes were constructed, and risks were estimated using Cox proportional hazards models. The homozygous variants of IL8 −251 and +396 were associated with 2-fold increased relative risks for GCC, but the highest risk observed was for the AGT/AGC haplotype of IL8 −251/+396/+781 (relative risk, 4.14; 95% confidence interval, 1.31-13.1). Variation within IL8 was not associated with ESCC. Few subjects had variation at the IL8RA SNP and no significant associations were observed for IL8RB SNPs or haplotypes with either GCC or ESCC. We conclude that variation in IL8 seems to increase the risk for GCC but not ESCC in this high-risk population. These variants could confer an altered IL8 expression pattern or interact with environmental factors to increase the risk for inflammation and GCC.

Polymorphisms in Interleukin -2, -6, and -10 Are Not Associated with Gastric Cardia or Esophageal Cancer in a High-Risk Chinese Population

Polymorphisms in Interleukin -2, -6, and -10 Are Not Associated with Gastric Cardia or Esophageal Cancer in a High-Risk Chinese Population

Helicobacter pylori infection and gastric atrophy: risk of adenocarcinoma and squamous-cell carcinoma of the esophagus and adenocarcinoma of the gastric cardia.

An inverse association between Helicobacter pylori infection and esophageal adenocarcinoma has been reported that may be attributed to reduced acidity from inducing atrophic gastritis and from producing ammonia. We examined associations between H. pylori infection, gastric atrophy, and the risk of esophageal adenocarcinoma, esophageal squamous-cell carcinoma, and gastric cardia adenocarcinoma in a large population-based case-control study in Sweden. Self-reported data were obtained during interviews, and serum was collected from 97 patients with incident esophageal adenocarcinoma, 85 patients with incident esophageal squamous-cell carcinoma, 133 patients with incident gastric cardia adenocarcinoma, and 499 randomly selected control subjects. Serum antibodies against whole H. pylori cell-surface antigens (HP-CSAs) and cytotoxin-associated gene A (CagA) antigens were assessed by an IgG enzyme-linked immunosorbent assay and immunoblotting, respectively. Gastric atrophy was assessed by serum levels of pepsinogen I. Multivariable logistic regression with adjustment for potential confounding factors was used to evaluate associations. H. pylori infection, assayed by HP-CSA or CagA antibodies, was statistically significantly associated with a reduced risk for esophageal adenocarcinoma (for HP-CSA antibodies, odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.2 to 0.6; for CagA antibodies, OR = 0.5, 95% CI = 0.3 to 0.8; for both, OR = 0.2, 95% CI = 0.1 to 0.5). Gastric atrophy was not associated with the risk for esophageal adenocarcinoma (OR = 1.1, 95% CI = 0.5 to 2.5). Serum CagA antibodies and gastric atrophy were associated with an increased risk for esophageal squamous-cell carcinoma (OR = 2.1, 95% CI = 1.1 to 4.0, and OR = 4.3, 95% CI = 1.9 to 9.6, respectively). The risk of gastric cardia adenocarcinoma was not associated with H. pylori infection. However, gastric atrophy was associated with an increased risk for gastric cardia adenocarcinoma (OR = 4.5, 95% CI = 2.5 to 7.8). Infection with H. pylori may reduce the risk of esophageal adenocarcinoma, but it is unlikely to do so by atrophy-reduced acidity. Gastric atrophy and infection with CagA-positive strains of H. pylori may increase the risk for esophageal squamous-cell carcinoma.

Effect of body mass index on adenocarcinoma of gastric cardia.

Obesity has been proved as one of the main risk factors for gastric cardia adenocarcinoma (GCA) in the West. The objective of our research was to evaluate the relationship between obesity and the risk of GCA in people from North China. A total of 300 patients who had been diagnosed as GCA and had accepted surgical operation at Beijing Cancer Hospital from 1995 to 2002 were enrolled. Data were collected from pathology materials and hospital records. Two hundred and fifty-eight healthy people who had accepted health examination at the same hospital during the same period were enrolled as controls. Height, weight and gender of them at the time of examination were also collected. Obesity was estimated by body mass index (BMI), computed as weight in kilograms per square surface area (Kg/m2). The degree of obesity was determined by using BMI< or =18.5, 24-27.9 and > or =28 (Kg/m2) as the cut-off points for underweight/normal, overweight and obesity, respectively. Associations with obesity were estimated by odds ratios (ORs) and 95 % confidence intervals (CIs). All ORs were adjusted for age and sex. The mean level of BMI was significantly lower in the patient group than that in the control group. The ORs for obesity in age groups 30-59 and 60-79 were 1.15 (95% CI=0.37-3.65) and 0.16 (95% CI=0.05-0.44) for males and 0.78 (95% CI=0.26-2.36) and 0.28 (95% CI=0.04-2.05) for females, respectively. The ORs for underweight were 2.42 (95% CI=0.56-10.53) and 4.68 (95% CI=1.13-19.40) for males in age subgroups 30-59 and 60-79 and 40.7 (95% CI=9.32-177.92) for females older than 60 yrs. BMI was significantly associated with GCA (P<0.01). Underweight people were at high risk for GCA. BMI is an independent risk factor for GCA. Underweight is positively associated with GCA.

Occupation and risk of esophageal and gastric cardia adenocarcinoma.

Adenocarcinomas of the esophagus and gastric cardia have risen dramatically in incidence over the past few decades, however, little research has been conducted on the occupational risk factors for these cancers. In this population-based case-control study, lifetime job histories were compared between cases of esophageal adenocarcinoma (n = 283), gastric cardia adenocarcinoma (n = 259), and population controls (n = 689). Odds ratios (OR) and 95% confidence intervals (CI) for ever employment and by duration in various occupational and industrial categories were calculated using unconditional logistic regression. The risk of esophageal adenocarcinoma was elevated for persons ever employed in administrative support (OR = 1.5; 95%CI = 1.0-2.1); financial, insurance, and real estate (OR = 1.6; 95%CI = 1.0-2.4); and health services (OR = 2.2; 95%CI = 1.2-3.9). The risk of gastric cardia adenocarcinoma was increased among transportation workers (OR = 1.7; 95%CI = 1.1-2.6), as well as among carpenters (OR = 1.8; 95%CI = 0.9-3.9) and workers in the furniture manufacturing industry (OR = 2.4; 95%CI = 0.9-6.3). However, we observed few duration-response relations between length of employment in any category and cancer risk. This study revealed associations of esophageal adenocarcinoma with employment in administrative support, health services, and a category of financial, insurance, and real estate industries, and of gastric cardia adenocarcinoma with transportation and certain woodworking occupations. Some of these findings may be due to the play of chance associated with the multiple comparisons made in this study. Our results suggest that, overall, workplace exposures play a minor role in the etiology and upward trend of esophageal and gastric cardia adenocarcinomas.

Inverse association between intake of cereal fiber and risk of gastric cardia cancer

Background & Aims: Recent data show that salivary nitrites form carcinogenic nitrosamines, especially at the gastric cardia. Wheat fiber has been shown to neutralize such mutagen formation. Our aim was to evaluate the association between dietary fiber and cancers of the esophageal and gastric cardia. Methods: We examined data from a large-scale population-based case-control study of risk factors for adenocarcinoma of the gastric cardia and esophagus and squamous cell carcinoma of the esophagus. Results: We found a strong dose-dependent inverse association between total dietary fiber intake and risk of gastric cardia adenocarcinoma, which was driven mainly by intake of cereal fiber. The odds ratio among individuals in the highest quartile of cereal fiber intake compared with the lowest was 0.3 (95% confidence interval, 0.2–0.5; P trend < 0.0001). High intake of cereal fiber was also associated with a moderately decreased risk of esophageal adenocarcinoma, but no linear dose-risk trend was observed. There was no association between dietary fiber and esophageal squamous cell carcinoma. Conclusions: High intake of cereal fiber may significantly lower the risk of gastric cardia cancer.GASTROENTEROLOGY 2001;120:387-391

Antioxidants and cancers of the esophagus and gastric cardia

Antioxidant vitamins have attracted considerable attention in previous studies of esophageal squamous-cell carcinoma, but dietary studies of adenocarcinoma of the esophagus and gastric cardia remain sparse. Treating these tumors as distinct diseases, we studied intakes of vitamin C, beta-carotene and alpha-tocopherol in a nationwide population-based case-control study in Sweden, with 185, 165, and 258 cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma, and gastric cardia adenocarcinoma, respectively, and 815 controls. Subjects with a high parallel intake of vitamin C, beta-carotene, and alpha-tocopherol showed a 40-50% decreased risk of both histological types of esophageal cancer compared with subjects with a low parallel intake. Antioxidant intake was not associated with the risk of gastric cardia adenocarcinoma. Separately, vitamin C and beta-carotene reduced the risk of esophageal cancers more than alpha-tocopherol. We found that antioxidant intake is associated with similar risk reductions for both main histological types of esophageal cancer. Our findings indicate that antioxidants do not explain the diverging incidence rates of the 2 histological types of esophageal cancer. Moreover, our data suggest that inverse associations with esophageal squamous-cell carcinoma and adenocarcinoma may be stronger among subjects under presumed higher oxidative stress due to smoking or gastroesophageal reflux, respectively. Our results may be relevant for the implementation of focused, cost-effective preventive measures.