Gastric Non-cardia Adenocarcinoma Research Articles

Demographic and lifestyle predictors of survival in patients with esophageal or gastric cancers

Risk factors for subtypes of esophageal and gastric cancer recently have been identified, but their effect on survival is unknown. Incident cases (n = 1142) from a population-based case-control study were followed-up from diagnosis (1993-1995) until 2000. Cox regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for esophageal and gastric cancer in relation to prediagnostic factors. Relative to distant stage, esophageal adenocarcinoma (EA) patients with localized disease had a decreased risk for death (HR, .22; 95% CI, .15-.31), followed by those with regional spread (HR, .32; 95% CI, .23-.45). Similar patterns were seen for the other tumor types. Except for other (non-cardia) gastric adenocarcinomas (OGA), higher household income (> or =15,000 US dollars/y vs. <15,000 US dollars/y) was associated with a 33%-38% decrease in risk for death. Prediagnosis body mass index (BMI) between 25 and 29.9 kg/m 2 was associated with longer survival for EA and OGA patients (EA: HR, .67; 95% CI, .51-.88) vs. BMI <25 kg/m(2). Women with esophageal squamous cell carcinoma (ES) and OGA experienced longer survival compared with men. Age, education, cigarette smoking, alcohol intake, gastroesophageal reflux disease, and nonsteroidal anti-inflammatory drug use did not consistently predict survival. Predictors of lengthened esophageal and gastric cancer survival included higher income (except in OGA), overweight (among EA and OGA patients), and female sex (among ES and OGA patients).

Prevalence ofHelicobacter pyloriinfection and intestinal metaplasia in subjects who had undergone surgery for gastric adenocarcinoma in Northwest Italy

To investigate the seroprevalence of Helicobacter pylori (H pylori) infection and its more virulent strains as well as the correlation with the histologic features among patients who had undergone surgery for gastric cancer (GC). Samples from 317 (184 males, 133 females, mean age 69+/-3.4 years) consecutive patients who had undergone surgery for gastric non-cardia adenocarcinoma were included in the study. Five hundred and fifty-five (294 males, 261 females, mean age 57.3+/-4.1 years) patients consecutively admitted to the Emergency Care Unit served as control. Histological examination of tumor, lymph nodes and other tissues obtained at the time of surgery represented the diagnostic "gold standard". An enzyme immunosorbent assay was used to detect serum anti-H pylori (IgG) antibodies and Western blotting technique was utilized to search for anti-CagA protein (IgG). Two hundred and sixty-one of three hundred and seventeen (82.3%) GC patients and 314/555 (56.5%) controls were seropositive for anti-H pylori (P<0.0001; OR, 3.58; 95%CI, 2.53-5.07). Out of the 317 cases, 267 (84.2%) were seropositive for anti-CagA antibody vs 100 out of 555 (18%) controls (P<0.0001; OR, 24.30; 95%CI, 16.5-35.9). There was no difference between the frequency of H pylori in intestinal type carcinoma (76.2%) and diffuse type cancer (78.8%). Intestinal metaplasia (IM) was more frequent but not significant in the intestinal type cancer (83.4% vs 75.2% in diffuse type and 72.5% in mixed type). Among the patients examined for IM, 39.8% had IM type I, 8.3% type II and 51.9% type III(type III vs others, P = 0.4). This study confirms a high seroprevalence of H pylori infection in patients suffering from gastric adenocarcinoma and provides further evidence that searching for CagA status over H pylori infection might confer additional benefit in identifying populations at greater risk for this tumor.

UNIQUE GLOBAL POPULATION

Purpose: Gastric cancer is the second leading cause of cancer with significant geographic variability. Cytokine polymorphisms (IL-IB, IL-1RA, IL-10, TNF-a) are associated with noncardia gastric adenocarcinoma in H. pylori infected patients. Multiple genotype carriage increases cancer risk. The background prevalence of polymorphisms in Europe and Asia is about 50% (IL-IB-511T: CT, <50%; TT, 4-21% and IL-10-1082A: GA, <50%; AA,28%). No previous studies have systematically evaluated host genetic, bacterial and dietary factors in a population-based study, nor polymorphisms in Latin America. Methods: We conducted aprospective, population-based, case-control study in Honduras, Central America. The western region (95% Mestizo) has a high incidence of gastric cancer, with standardized annual incidence rates of 39 and 21(M,F), often in younger patients (25%,12% under ages 50,35). Cases were enrolled at the Western Regional Hospital. Controls were selected from houses at random using mapping from the Honduran government thru UNESCO. Unique image-based software established dietary and micronutrient intake. Results: We have enrolled 258 subjects, with genetic data available for 110 controls and 65 cases(IL-1B,IL-10). The rates of high risk polymorphisms are the highest reported, defining a significant genetic risk in the Honduran population. In the controls, the IL-1B-511T+ prevalence was 84% (95% CI, 81–88%) with CT 57%, TT 27%. The IL-10-1082A+ prevalence was 93% (95% CI, 91–95%) with GA 33%, AA 60%. Endemic H. pylori infection was confirmed (88%). Nutrient data suggests antioxidant deficiencies (alphacarotene, selenium). Haplotype Analysis shows that 89% of the general population is at increased risk for gastric adenocarcinoma. Nearly 20% of the population was homozygotic for both polymorphisms (TT/AA), while less than 1% carried the wild type (CC/GG). Haplotype prevalence was increased in the cancer group, shy of statistical significance (p = 0.11), due to sample size given the high backround genotype prevalence. Conclusions: This is the first study of gastric cancer cytokine polymorphisms in Latin America and the Latino population. We have identified a unique population with endemic genetic susceptibility, defined by the highest reported prevalence of haplotypes of cytokine polymorphisms in the setting of endemic H. pylori infection. Host genetics, H. pylori, and diet explain the high incidence and provide an opportunity to design intervention studies.

Nonsteroidal anti-inflammatory drug use associated with reduced incidence of adenocarcinomas of the esophagus and gastric cardia that overexpress cyclin D1: a population-based study.

This study was undertaken to determine whether selected risk factors for esophageal and gastric cancer are associated with tumors that overexpress cyclin D1. Archived tumor tissue was available for 630 esophageal and gastric cancer patients who participated in a population-based case-control study. Patients were categorized into case groups based on whether protein overexpression of the cyclin D1 gene, as assessed by immunohistochemistry, was present (cyclin D1+, n = 285) or not (cyclin D1-, n = 345) in the tumor. The distribution of risk factors in each of these case groups was then compared with the distribution among the 695 controls. Multivariate-adjusted odds ratios (OR) for esophageal adenocarcinoma were reduced in relation to use of aspirin and other nonsteroidal anti-inflammatory drug (NSAID) use but only among patients with cyclin D1+ tumors (0.45, 95% confidence interval [CI] = 0.26, 0.79) and not among those with cyclin D1- tumors (1.12, 95% CI = 0.67, 1.86). A similar pattern was observed for gastric cardia adenocarcinomas. In contrast, ORs for esophageal squamous cell carcinoma and noncardia gastric adenocarcinomas in relation to NSAID use were reduced, regardless of cyclin D1 status. ORs did not vary with cyclin D1 status in relation to alcohol, body size, or cigarette smoking, with the following exception; for noncardia gastric adenocarcinomas the cyclin D1- tumors showed a 2-fold elevation in the OR with ever smoking. These data suggest that the reduction in risk associated with NSAID use may be restricted to those esophageal and gastric cardia adenocarcinomas that overexpress cyclin D1.

Population attributable risks of esophageal and gastric cancers.

Several risk factors have been identified for esophageal adenocarcinoma, gastric cardia adenocarcinoma, esophageal squamous cell carcinoma, and noncardia gastric adenocarcinoma, but no study has comprehensively examined their contributions to the cancer burden in the general population. Herein, we estimate the population attributable risks (PARs) for various risk factors observed in a multicenter population-based case-control study. We calculated PARs by using 293 patients with esophageal adenocarcinoma, 261 with gastric cardia adenocarcinoma, 221 with esophageal squamous cell carcinoma, 368 with noncardia gastric adenocarcinoma, and 695 control subjects. We included smoking for all four tumor types and Helicobacter pylori infection for noncardia gastric adenocarcinoma as established causal risk factors as well as several other factors for which causality is under evaluation. Ever smoking, body mass index above the lowest quartile, history of gastroesophageal reflux, and low fruit and vegetable consumption accounted for 39.7% (95% confidence interval [CI] = 25.6% to 55.8%), 41.1% (95% CI = 23.8% to 60.9%), 29.7% (95% CI = 19.5% to 42.3%), and 15.3% (95% CI = 5.8% to 34.6%) of esophageal adenocarcinomas, respectively, with a combined PAR of 78.7% (95% CI = 66.5% to 87.3%). Ever smoking and body mass index above the lowest quartile were responsible for 45.2% (95% CI = 31.3% to 59.9%) and 19.2% (95% CI = 4.9% to 52.0%) of gastric cardia adenocarcinomas, respectively, with a combined PAR of 56.2% (95% CI = 38.1% to 72.8%). Ever smoking, alcohol consumption, and low fruit and vegetable consumption accounted for 56.9% (95% CI = 36.6% to 75.1%), 72.4% (95% CI = 53.3% to 85.8%), and 28.7% (95% CI = 11.1% to 56.5%) of esophageal squamous cell carcinomas, respectively, with a combined PAR of 89.4% (95% CI = 79.1% to 95.0%). Ever smoking, history of gastric ulcers, nitrite intake above the lowest quartile, and H. pylori infection were responsible for 18.3% (95% CI = 6.5% to 41.8%), 9.7% (95% CI = 5.4% to 16.8%), 40.7% (95% CI = 23.4% to 60.7%), and 10.4% (95% CI = 0.3% to 79.6%) of noncardia gastric adenocarcinomas, respectively, with a combined PAR of 59.0% (95% CI = 16.2% to 91.4%). In this population, a few known risk factors account for a majority of esophageal and gastric cancers. These results suggest that the incidence of these cancers may be decreased by reducing the prevalence of smoking, gastroesophageal reflux, and being overweight and by increasing the consumption of fruits and vegetables.

Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms

Background & Aims: Genetic variations in proinflammatory and anti-inflammatory cytokine genes influence individual response to carcinogenic exposures. Polymorphisms in interleukin (IL)-1β and its endogenous receptor antagonist are associated with risk of Helicobacter pylori-related gastric cancer. The aim of this study was to evaluate the role of proinflammatory cytokine gene polymorphisms in gastric and esophageal cancers defined by anatomic subsite. Methods: We assessed polymorphisms of the IL-1 gene cluster and 4 other cytokine genes in a population-based case-control study of upper gastrointestinal cancers, including gastric cardia (n = 126) and noncardia adenocarcinoma (n = 188), esophageal squamous cell carcinoma (n = 53), and adenocarcinoma (n = 108), and frequency-matched controls (n = 212). ORs for the different cancers were computed from logistic regression models adjusted for potential confounding factors. Results: Proinflammatory genotypes of tumor necrosis factor α and IL-10 were each associated with more than doubling of the risk of noncardia gastric cancer. Carriage of multiple proinflammatory polymorphisms of IL-1B o IL-1 receptor antagonist, tumor necrosis factor A, and IL-10 conferred greater risk, with ORs (and 95% confidence intervals) of 2.8 (1.6–5.1) for one, 5.4 (2.7–10.6) for 2, and 27.3 (7.4–99.8) for 3 or 4 high-risk genotypes. In contrast, these polymorphisms were not consistently related to the risks of esophageal or gastric cardia cancers. Polymorphisms in IL-4 and IL-6 were not associated with any of the cancers studied. Conclusions: A proinflammatory cytokine genetic profile increases the risk of noncardia gastric adenocarcinoma but not other upper gastrointestinal cancers, possibly by inducing a hypochlorhydric and atrophic response to gastric H. pylori infection.

Prospective study of serum retinol, beta-carotene, beta-cryptoxanthin, and lutein/zeaxanthin and esophageal and gastric cancers in China.

This study examined the relationship between pretrial serum concentrations of retinol, beta-carotene, beta-cryptoxanthin, and lutein/zeaxanthin and the subsequent risk of developing esophageal squamous cell carcinoma and gastric cardia or non-cardia adenocarcinoma in subjects selected from a randomized nutritional intervention trial in Linxian, China, a region with epidemic rates of esophageal and gastric cardia cancer. We used a stratified case-cohort design to select cohort members for inclusion in this study. In all we measured serum concentrations of the above vitamins in 590 esophageal, 395 gastric cardia, and 87 gastric non-cardia case subjects as well as in 1053 control subjects. Relative risks (RRs) were estimated using Cox proportional hazards models. Median values in our cohort were low for serum retinol (33.6 microg/dl), beta-carotene (4.3 microg/dl), and beta-cryptoxanthin (3.5 microg/dl), but were high for lutein/zeaxanthin (40.0 microg/dl). Gastric cardia cancer incidence fell 10% for each quartile increase in serum retinol (RR = 0.90, 95% CI = 0.83-0.99). For esophageal cancer, an inverse association with retinol levels was found only in male non-smokers (RR = 0.79 per quartile increase, 95% CI = 0.63-0.99). For gastric non-cardia cancer, an inverse association was limited to subjects 50 years old or younger (RR = 0.58 per quartile, 95% CI = 0.31-0.96). For beta-cryptoxanthin there was a borderline significant protective association for gastric non-cardia cancer (RR = 0.88 per quartile, 95% CI = 0.76-1.0). In contrast, we found the incidence of gastric non-cardia cancer increased (RR = 1.2 per quartile, 95% CI = 1.0-1.3) with increasing concentration of serum lutein/zeaxanthin. In this population, we found that low retinol and high lutein/zeaxanthin concentrations increased the risks of gastric cardia and gastric non-cardia cancer respectively. We found that there were no strong associations between any of the other analytes and any of the cancer sites.

#8 Esophageal and gastric cancer in the united states

PURPOSE: Historically, esophageal and gastric cancers have been considered as two cancers. Esophageal cancers were predominantly squamous cell carcinomas, stomach cancers were adenocarcinomas, tumors arose throughout each of the two organs, and rates for each were higher among blacks than whites. Recent observations suggest that there may be at least three, if not four, distinct epidemiologic and potentially etiologic entities: squamous cell carcinoma of the esophagus (SCE), adenocarcinoma of the esophagus (ACE) (arising in the distal region), proximal stomach or gastric cardia adenocarcinoma (GCA), and noncardia gastric adenocarcinoma (NGA). METHODS: We analyzed SEER incidence data for 1974–78 to 1994–98 by anatomic site and histologic type to describe these potentially different tumors, review known or suspected risk factors, and describe the trends in prevalence of these factors. RESULTS: SCE rates decreased after 1988 for all race-gender groups. In contrast, the incidence of ACE increased more than 400% among white males, and ACE rates surpassed those of SCE after 1988. ACE rates increased more than 300% among white females, rose 100% among black males, and also showed an upward trend among black women. NGA trends were generally downward. However, similar to ACE, GCA rates increased from 1974–78 to 1984–88, although to a lesser extent, and appear to have stabilized since then. With the decrease in NGA rates and the increase then stabilization in GCA rates, rates of GCA and NGA among white men were similar in 1994–98. CONCLUSIONS: Declines in the prevalence of smoking and drinking and increases in consumption of fresh fruits and vegetables may contribute to the downward trends in SCE. Increases in gastroesophageal reflux disease and obesity, and declines in Helicobactor pylori ( H. pylori ) infection may contribute to the upward trends in ACE. Reductions in NGA may be related to improved diet and reductions in smoking and H. pylori prevalence. Factors contributing to the rising incidence of GCA of the cardia during the 1970s and 1980s, but not the 1990s, are less clear.

Intracellular bacteria in Hodgkin's disease and sclerosing mediastinal B-cell lymphoma: sign of a bacterial etiology?

The aetiology of Hodgkin's disease is still unknown more than 160 years after its original description. In recent years a viral aetiology was the preferred hypothesis. Epidemiological, clinical, laboratory, and histological findings, however, point rather to a bacterial aetiology. In the histological work-up of tissues from patients suffering from malignant lymphoma periodic acid-Schiff (PAS) stains are routinely done. In several bacterial infections intracellular PAS-positive material can be observed. We examined PAS-stained slides at magnifications of 1000x of six Hodgkin and twelve Non-Hodgkin patients. We found PAS-positive diastase resistant intracellular rods and spheres in all Hodgkin patients and in all of the six patients suffering from sclerosing mediastinal B-cell lymphomas, but not the other Non-Hodgkin lymphomas. The diastase resistant PAS-positive structures are compatible with intracellular bacteria. After gastric MALT-lymphoma and gastric non-cardia adenocarcinoma it appears that Hodgkin's disease and sclerosing mediastinal B-cell lymphomas may also be human tumors related bacteria.

Intracellular bacteria in Hodgkin's disease and sclerosing mediastinal B-cell lymphoma: sign of a bacterial etiology?

The aetiology of Hodgkin's disease is still unknown more than 160 years after its original description. In recent years a viral aetiology was the preferred hypothesis. Epidemiological, clinical, laboratory, and histological findings, however, point rather to a bacterial aetiology. In the histological work-up of tissues from patients suffering from malignant lymphoma periodic acid-Schiff (PAS) stains are routinely done. In several bacterial infections intracellular PAS-positive material can be observed. We examined PAS-stained slides at magnifications of 1000x of six Hodgkin and twelve Non-Hodgkin patients. We found PAS-positive diastase resistant intracellular rods and spheres in all Hodgkin patients and in all of the six patients suffering from sclerosing mediastinal B-cell lymphomas, but not the other Non-Hodgkin lymphomas. The diastase resistant PAS-positive structures are compatible with intracellular bacteria. After gastric MALT-lymphoma and gastric non-cardia adenocarcinoma it appears that Hodgkin's disease and sclerosing mediastinal B-cell lymphomas may also be human tumors related bacteria.

Unchanging trend of adenocarcinoma of the esophagus and gastric cardia in Taiwan: a 15-year experience in a single center.

Chronic gastroesophageal reflux disease is closely associated with esophageal adenocarcinoma and gastric cardia carcinoma, and esophageal adenocarcinoma and gastric cardia carcinoma have both been increasing in Western countries recently. Gastroesophageal reflux disease is not rare in Taiwan, but the frequency of occurrence of esophageal adenocarcinoma or gastric cardia carcinoma has not been studied here to date. Patients diagnosed with esophageal and gastric cancers at this hospital between 1981 and 1995 were recruited using the hospital tumor registry database. There were 45, 1546, 970, and 4167 patients diagnosed with esophageal adenocarcinoma, esophageal squamous cell carcinoma, gastric cardia carcinoma, and gastric noncardia adenocarcinoma, respectively. The ratios of esophageal adenocarcinoma versus esophageal squamous cell carcinoma among the three cohorts were 0.030, 0.016, and 0.041, respectively (trend, P = 0.086). The corresponding values for gastric cardia carcinoma versus gastric noncardia adenocarcinoma were 0.252, 0.232, and 0.218, respectively (trend, P = 0.256). The ratios of esophageal adenocarcinoma versus esophageal squamous cell carcinoma and of gastric cardia carcinoma versus gastric noncardia adenocarcinoma have not risen in the three cohorts. Unlike the situation in Western countries, the incidence of esophageal adenocarcinoma and gastric cardia carcinoma versus esophageal squamous cell carcinoma and gastric noncardia adenocarcinoma have not increased over the past 15 years among the Chinese in Taiwan. Although gastroesophageal reflux disease is common here, its definite pathogenesis leading to esophageal adenocarcinoma or gastric cardia carcinoma remains unresolved.

Family history of cancer and risk of esophageal and gastric cancers in the United States.

The worldwide rates for histology- and subsite-specific types of esophageal and gastric cancer reveal strikingly divergent patterns. The contribution of environmental and genetic factors has been explored in several high-incidence areas, but data on genetic influences are scarce for Western countries. Using data from a multicenter, population-based, case-control study on 1,143 cases and 695 controls in the United States, we evaluated whether a family history of digestive or other cancers was associated with an increased risk of esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261) or non-cardia gastric adenocarcinoma (n = 368). After adjusting for other risk factors, individuals reporting a family history of digestive cancers experienced no increased risk of either type of esophageal cancer but they were prone to adenocarcinomas of the gastric cardia [odds ratio (OR) = 1.34, 95% confidence interval (CI) 0.91-1.97] and non-cardia segments (OR =1.46, 95% CI 1.03-2.08). This familial tendency, particularly for non-cardia gastric tumors, was largely explained by an association with family history of stomach cancer (OR = 2.52, 95% CI 1.50-4.23). In addition, family history of breast cancer was associated with increased risks of esophageal adenocarcinoma (OR = 1.74, 95% CI 1.07-2.83) and non-cardia gastric adenocarcinoma (OR = 1.76, 95% CI 1.09-2.82). Also seen were non-significant familial associations of esophageal squamous-cell cancer with prostate cancer as well as non-cardia gastric cancer with leukemia and brain tumors, though these relationships must be interpreted with caution. Our data point to the role of familial susceptibility to gastric cancer, but not to any form of esophageal cancer, in the United States.

Prospective study of tooth loss and incident esophageal and gastric cancers in China.

To determine the association between tooth loss and the risk of developing esophageal squamous cell carcinoma, gastric cardia adenocarcinoma, or gastric non-cardia adenocarcinoma in a prospective study. Cox proportional hazards regression was used to examine these associations in a 28,868-person cohort followed prospectively for 5.25 years. The baseline questionnaire included questions regarding tooth loss, and individuals reporting lost teeth had their teeth counted by study personnel. The analytic cohort included 620 esophagus, 431 gastric cardia, and 102 gastric non-cardia cancer cases. Tooth loss was associated with a significantly elevated risk of developing all three cancers. When examined as median splits, tooth loss was associated with a relative risk (RR) (95% confidence interval, CI) of 1.3 (1.1-1.6) in the esophagus, 1.3 (1.0-1.6) in the gastric cardia, and 1.8 (1.1-3.0) in the gastric non-cardia. Further analysis demonstrated that this increased risk was most strongly associated with the loss of the first few teeth and was primarily confined to the younger members of our cohort. In this cohort tooth loss increased the risk of developing upper gastrointestinal cancer. We hypothesize that this may be related to alterations in oral bacterial flora and subsequent increases in the in-vivo production of carcinogens such as nitrosamines.

Gastroesophageal reflux disease, use of H2 receptor antagonists, and risk of esophageal and gastric cancer.

The incidence of esophageal adenocarcinoma has risen rapidly in the past two decades, for unknown reasons. The goal of this analysis was to determine whether gastroesophageal reflux disease (GERD) or the medications used to treat it are associated with an increased risk of esophageal or gastric cancer, using data from a large population-based case-control study. Cases were aged 30-79 years, newly diagnosed with esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261), or non-cardia gastric adenocarcinoma (n = 368) in three areas with population-based tumor registries. Controls (n = 695) were chosen by random digit dialing and from Health Care Financing Administration rosters. Data were collected using an in-person structured interview. History of gastric ulcer was associated with an increased risk of non-cardia gastric adenocarcinoma (OR 2.1, 95% CI 1.4-3.2). Risk of esophageal adenocarcinoma increased with frequency of GERD symptoms; the odds ratio in those reporting daily symptoms was 5.5 (95% CI 3.2-9.3). Ever having used H2 blockers was unassociated with esophageal adenocarcinoma risk (OR 0.9, 95% CI 0.5-1.5). The odds ratio was 1.3 (95% CI 0.6-2.8) in long-term (4 or more years) users, but increased to 2.1 (95% CI 0.8-5.6) when use in the 5 years prior to the interview was disregarded. Risk was also modestly increased among users of antacids. Neither GERD symptoms nor use of H2 blockers or antacids was associated with risk of the other three tumor types. Individuals with long-standing GERD are at increased risk of esophageal adenocarcinoma, whether or not the symptoms are treated with H2 blockers or antacids.

Allelic variation in Helicobacter pylori: progress but no panacea

See article on page 499 Helicobacter pylori colonisation in the stomach is associated with increased risk for the development of peptic ulcer disease and non-cardia gastric adenocarcinoma.1 However, the incidences...

Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia.

Incidence rates have risen rapidly for esophageal adenocarcinoma and moderately for gastric cardia adenocarcinoma, while rates have remained stable for esophageal squamous cell carcinoma and have declined steadily for noncardia gastric adenocarcinoma. We examined anthropometric risk factors in a population-based case-control study of esophageal and gastric cancers in Connecticut, New Jersey, and western Washington. Healthy control subjects (n = 695) and case patients with esophageal squamous cell carcinoma or noncardia gastric adenocarcinoma (n = 589) were frequency-matched to case patients with adenocarcinomas of esophagus or gastric cardia (n = 554) by 5-year age groups, sex, and race (New Jersey only). Classification of cases by tumor site of origin and histology was determined by review of pathology materials and hospital records. Data were collected using in-person structured interviews. Associations with obesity, measured by body mass index (BMI), were estimated by odds ratios (ORs). All ORs were adjusted for geographic location, age, sex, race, cigarette smoking, and proxy response status. The ORs for esophageal adenocarcinoma rose with increasing adult BMI. The magnitude of association with BMI was greater among the younger age groups and among nonsmokers. The ORs for gastric cardia adenocarcinoma rose moderately with increasing BMI. Adult BMI was not associated with risk of esophageal squamous cell carcinoma or noncardia gastric adenocarcinoma. Increasing prevalence of obesity in the United States population may have contributed to the upward trends in esophageal and gastric cardia adenocarcinomas.

Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia

Incidence rates for adenocarcinomas of the esophagus and gastric cardia have risen steeply over the last few decades. To determine risk factors for these tumors, we conducted a multicenter, population-based, case-control study. The study included 554 subjects newly diagnosed with esophageal or gastric cardia adenocarcinomas, 589 subjects newly diagnosed with esophageal squamous cell carcinoma or other gastric adenocarcinomas, and 695 control subjects. Estimates of risk (odds ratios [ORs] and corresponding 95% confidence intervals [CIs]) were calculated for the four tumor types separately and for esophageal and gastric cardia adenocarcinomas combined. Risk of esophageal and gastric cardia adenocarcinomas combined was increased among current cigarette smokers (OR = 2.4; 95% = 1.7-3.4), with little reduction observed until 30 years after smoking cessation; this risk rose with increasing intensity and duration of smoking. Risk of these tumors was not related to beer (OR = 0.8; 95% CI = 0.6-1.1) or liquor (OR = 1.1; 95% CI = 0.8-1.4) consumption, but it was reduced for drinking wine (OR = 0.6; 95% CI = 0.5-0.8). Similar ORs were obtained for the development of noncardia gastric adenocarcinomas in relation to tobacco and alcohol use, but higher ORs were obtained for the development of esophageal squamous cell carcinomas. For all four tumor types, risks were higher among those with low income or education. Smoking is a major risk factor for esophageal and gastric cardia adenocarcinomas, accounting for approximately 40% of cases. Because of the long lag time before risk of these tumors is reduced among ex-smokers, smoking may affect early stage carcinogenesis. The increase in smoking prevalence during the first two thirds of this century may be reflected in the rising incidence of these tumors in the past few decades among older individuals. The recent decrease in smoking may not yet have had an impact.

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.