Gastric Non-cardia Adenocarcinoma Research Articles

S1386 Diverging Patterns of Cardia and Non-Cardia Gastric Adenocarcinoma Incidence by Race and Age in the United States From 2000-2018

Introduction: Gastric adenocarcinoma is the fifth-leading cause of cancer incidence and fourth-leading cause of cancer mortality worldwide. In the United States (US), racial groups differ in their incidence of cardia (CGA) and non-cardia (NCGA) gastric adenocarcinomas. There have been few studies published observing secular trends in incidence of both CGA and NCGA stratified by race in the US. Methods: Age-adjusted incidence rates and trends of CGA and NCGA in adults aged ≥ 25 years were calculated using data form 18 registries reporting to the Surveillance, Epidemiology, and End Results (SEER) Program from years 2000-2018. Race/ethnicity was classified as non-Hispanic White, non-Hispanic Black, American Indian/Alaskan Native, Asians/Pacific Islanders, and Hispanic. Analysis was also stratified by age (25-49 and ≥50). We used joinpoint regression to assess annual percent change (APC), average annual percent change (AAPC), and corresponding 95% confidence intervals (CIs). Results: The incidence of NCGA decreased in all racial groups, regardless of age, across the study period. The incidence of CGA also decreased in all racial groups among individuals ≥50 (Table 1). However, among individuals 25-49, the incidence of CGA is increasing among non-Hispanic Whites (AAPC = 1.0, 95% CI; 0.3, 1.7), Asian/Pacific Islanders (AAPC = 2.5, 95% CI; -0.3, 5.4), and Hispanics (AAPC = 2.3, 95% CI; 0.9, 3.8) (Figure 1). Conclusion: NCGA incidence is decreasing in all racial and age groups. By contrast, CGA incidence in increasing in the young among certain racial/ethnic groups. Clinicians and policy makers must be cognizant of these recent and worrisome trends. Moreover, appropriate cancer prevention programs are needed to target these at-risk populations.Table 1.: Average annual percent change in cardia and non-cardia gastric cancer incidence rates by race and age: SEER 2000-2018 SEER, Surveillance, Epidemiology and End Results; AAPC, average annual percent change. † Lack of data to analyze AAPC.Figure 1.: Age- and race-specific cardia gastric cancer incidence trends in the SEER data, 2000-2018 A. Non-Hispanic Whites aged 25-49 B. Non-Hispanic Asian/Pacific Islanders aged 25-49 C. Hispanics aged 25-49 D. Non-Hispanic Whites aged ≥50 E. Non-Hispanic Asian/Pacific Islanders aged ≥50 F. Hispanics aged ≥50

S1385 Impact of Race and Ethnicity on Risks of Cardia and Non-Cardia Gastric Adenocarcinomas in the U.S., 2000-2019: A Large Single-Center Retrospective Cohort Study

S1385 Impact of Race and Ethnicity on Risks of Cardia and Non-Cardia Gastric Adenocarcinomas in the U.S., 2000-2019: A Large Single-Center Retrospective Cohort Study

731 RISK OF ESOPHAGEAL AND GASTRIC ADENOCARCINOMA IN MEN RECEIVING ANDROGEN DEPRIVATION THERAPY FOR PROSTATE CANCER

Abstract There is an unexplained male predominance in the incidence of esophageal (EAC) and non-cardia gastric adenocarcinoma (GAC) which cannot be explained by known risk factors. Differences in the exposures to sex hormones may play a part in the observed sex difference. This study aimed to test the hypothesis that androgens increase the risk of EAC, cardia GAC, and non-cardia GAC. We analysed a matched cohort based on a national Swedish database of prostate cancer patients. Methods Prostate cancer patients receiving androgen deprivation therapy (ADT) were the exposed group. Prostate cancer-free men from the general population were randomly selected and matched to the index case by birth year and county of residence, forming the unexposed control group. The participants were followed until a diagnosis of esophageal or gastric cancer, death, emigration, or end of the study period. The risk of esophageal adenocarcinoma, cardia gastric adenocarcinoma, non-cardia gastric adenocarcinoma, and esophageal squamous-cell carcinoma among ADT-exposed compared to unexposed was calculated by multivariable Cox proportional hazard regression. The hazard ratios and 95% confidence intervals were adjusted for confounders. Results There was a risk reduction of non-cardia gastric adenocarcinoma among ADT-users compared to non-users (HR 0.49 [95% CI 0.24–0.98]). No such decreased risk was found for esophageal adenocarcinoma (HR 1.17 [95% CI 0.60–2.32]), cardia gastric adenocarcinoma (HR 0.99 [95% CI 0.40–2.46]), or esophageal squamous cell carcinoma (HR 0.99 [95% CI 0.31–3.13]). Conclusion This study indicates that androgen deprivation therapy decreases the risk of non-cardia gastric adenocarcinoma, while no decreased risk was found for esophageal adenocarcinoma, cardia gastric adenocarcinoma, or esophageal squamous-cell carcinoma.

Population Attributable Risks of Subtypes of Esophageal and Gastric Cancers in the United States.

To help target preventive strategies, we estimated US population attributable risks (PARs) of demographic and potentially modifiable risk factors for esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric noncardia adenocarcinoma (GNCA). We prospectively examined the associations for risk factors and these cancers in 490,605 people in the National Institutes of Health-the American Association of Retired Persons Diet and Health cohort Diet and Health Study cohort from 1995 to 2011. Exposures were obtained from the baseline questionnaire. Diagnoses of gastroesophageal reflux disease were extracted for a subset of eligible National Institutes of Health-the American Association of Retired Persons Diet and Health cohort subjects through linkage to Medicare and then multiply imputed for non-Medicare-eligible subjects. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazards regression. Adjusted population attributable risks were calculated for the US population aged 50-71 years by combining the hazard ratios with the estimated joint distribution of risk factor prevalence from the 2015 National Health Interview Survey. Smoking remained the most important risk factor for ESCC and was estimated to cause more than 1/3 of EAC and GCA and 1/10 of GNCA. Obesity and gastroesophageal reflux disease were associated with more than 1/2 of EAC and 1/3 of GCA. Compared with each lowest-risk level category, common risk factors were estimated to be associated with 73.7% of ESCC (95% confidence interval [CI]: 62.1%-85.4%), 70.3% of EAC (95% CI: 64.4%-76.2%), 69.3% of GCA (95% CI: 61.0%-77.7%), and 33.6% of GNCA (95% CI: 21.7%-45.5%). These factors accounted for a large proportion of esophageal and gastric cancers in the United States, highlighting opportunities for education and intervention to reduce the burden of these highly fatal cancers.

Risk of esophageal and gastric adenocarcinoma in men receiving androgen deprivation therapy for prostate cancer

The aim of this study was to explore the male predominance in esophageal and gastric adenocarcinoma by evaluating the preventive potential of androgen deprivation therapy (ADT). This matched cohort study was based on a national Swedish database of prostate cancer patients in 2006–2013. Prostate cancer patients receiving ADT were the exposed group. Prostate cancer-free men from the general population were randomly selected and matched to the index case by birth year and county of residence, forming the unexposed control group. The participants were followed until a diagnosis of esophageal or gastric cancer, death, emigration, or end of the study period. The risk of esophageal adenocarcinoma, cardia gastric adenocarcinoma, non-cardia gastric adenocarcinoma, and esophageal squamous-cell carcinoma among ADT-exposed compared to unexposed was calculated by multivariable Cox proportional hazard regression. The hazard ratios (HRs) and 95% confidence intervals (CIs) were adjusted for confounders. There was a risk reduction of non-cardia gastric adenocarcinoma among ADT-users compared to non-users (HR 0.49 [95% CI 0.24–0.98]). No such decreased risk was found for esophageal adenocarcinoma (HR 1.17 [95% CI 0.60–2.32]), cardia gastric adenocarcinoma (HR 0.99 [95% CI 0.40–2.46]), or esophageal squamous cell carcinoma (HR 0.99 [95% CI 0.31–3.13]). This study indicates that androgen deprivation therapy decreases the risk of non-cardia gastric adenocarcinoma, while no decreased risk was found for esophageal adenocarcinoma, cardia gastric adenocarcinoma, or esophageal squamous-cell carcinoma.

ABO genotypes and the risk of esophageal and gastric cancers

BackgroundBlood type has been associated with the risk of gastric cancer, but few studies have examined the association with esophageal squamous cell carcinoma (ESCC).MethodsWe conducted a case-control study using genotyping data of Chinese individuals, including cases of 2022 ESCC, 1189 gastric cardia adenocarcinoma, 1161 gastric noncardia adenocarcinoma, and 2696 controls. Genetic blood type was imputed using three single nucleotide polymorphisms. We used logistic regression to examine the association between blood type and the risk of each cancer.ResultsCompared to blood type O, the risk of ESCC was significantly elevated for blood type B and AB, with the highest risk for type AB (OR, 95%CI: 1.34, 1.07–1.67). Analysis of genotype suggested that the association of ESCC was from carrying the B allele. Similarly, blood type was significantly associated with gastric noncardia adenocarcinoma (P < 0.001) with risk significantly elevated in type A (1.37, 1.14–1.65) and AB (1.44, 1.10–1.89) compared to type O. Blood type was not associated with gastric cardia adenocarcinoma (P = 0.13).ConclusionsThis study provides novel insights into the association between blood type and the risk of ESCC and restricted previously observed association to only gastric noncardia cancer, providing important evidence to clarify the pattern of association and suggesting mechanisms of action.

Disentangling the obesity paradox in upper gastrointestinal cancers: Weight loss matters more than body mass index

ObjectivesThe obesity paradox, whereby obesity appears to confer protection against cancer-related mortality, remains controversial. This has not yet been evaluated in upper gastrointestinal cancers. DesignsWe identified esophageal, cardia, and non-cardia gastric adenocarcinomas in the Veterans Health Administration between 2006–2016. Multivariable Cox proportional hazard models evaluate the impact of BMI at- and prior to- cancer diagnosis on mortality, adjusting for demographics, clinical characteristics, weight loss, and clinical stage (early: T1B/2N0; locally advanced: ≥T2N+). ResultsWe identify 1308 patients: 99 % male, median 66 years. In early disease, relative to BMI 30, BMI 18 and 20 at diagnosis had increased risk of death (HR 1.83, 95 %CI: 1.38–2.44 and HR 1.50, 95 %CI: 1.20–1.87, respectively, p < 0.0001). Patients with BMI > 30 did not. In locally advanced disease, at diagnosis BMI 18 (HR 1.58, 95 %CI: 1.0001–1.48, p = 0.05), BMI 20 (HR 1.46, 95 %CI: 1.01–2.09, p = 0.04), and BMI 25 (HR 1.20, 95 %CI: 1.04–1.38, p = 0.01) had increased risk of death, but BMI > 30 did not.In models assessing premorbid BMI and weight loss, increasing amounts of weight loss were associated with mortality independent of BMI in early cancers. For locally advanced cancers, without weight loss, there was no association with death, regardless of BMI. ConclusionThe predominant driver of mortality across clinical stages is weight loss. The obesity paradox appears to exist in early stage disease only. Future studies should investigate mechanisms for the obesity paradox, accompanying physiologic changes with weight loss preceding diagnosis, and if patients with low BMI and weight loss benefit from early nutritional support.

Eastern European and Asian-born populations are prone to gastric cancer: an epidemiologic analysis of foreign-born populations and gastric cancer.

BackgroundThe highest incidence of gastric cancer is in East Asia, corresponding to a high prevalence of Helicobacter pylori (H. pylori), yet other regions with a similarly high prevalence of H. pylori have lower cancer rates. Foreign-born persons who immigrate to the United States are thought to remain at high-risk for gastric cancer, but this has not been confirmed by large population-based studies.MethodsWe evaluated total and foreign-born populations in metropolitan statistical areas (MSAs). Cardia and non-cardia gastric adenocarcinomas diagnosed between 2006 and 2016 were identified using the Surveillance, Epidemiology, and End Results Program. Generalized linear regression models determined whether the incidence of gastric cancer in each MSA was associated with specific foreign-born populations.ResultsAmong 32 MSAs, we identified 55,937 patients with gastric adenocarcinoma. A greater percentage of Eastern European-born individuals in an MSA was associated with a higher incidence of cardia cancers (coefficient 1.32, P=0.02). Evaluating Asian-born populations alone, a greater percentage of Japanese-born individuals was associated with a higher incidence of non-cardia cancers (coefficient 2.48, P=0.03), whereas Korean or Chinese origin was not associated with a significantly higher risk.ConclusionsOn a population level, a greater percentage of Eastern European-born individuals is associated with a higher incidence of cardia gastric adenocarcinomas. Among Asian-born individuals, Korean or Chinese origin was not associated with a significantly higher risk, but a greater percent of persons born in other Asian countries, including Japan, was associated with a higher incidence of non-cardia gastric adenocarcinomas in an MSA.

Population-Based Analysis of Differences in Gastric Cancer Incidence Among Races and Ethnicities in Individuals Age 50 Years and Older

There are racial and ethnic differences in the incidence of gastric adenocarcinoma worldwide and in the US. Based on a decision analysis, screening for noncardia gastric adenocarcinoma might be cost-effective for non-White individuals 50 years or older. However, a lack of precise, contemporary information on gastric adenocarcinoma incidence in specific anatomic sites for this age group has impeded prevention and early detection programs in the US. We aimed to estimate the differences in gastric adenocarcinoma incidence in specific anatomic sites among races and ethnicities in individuals 50 years or older. We analyzed California Cancer Registry data from 2011 through 2015 to estimate incidences of gastric adenocarcinoma in specific anatomic sites for non-Hispanic White (NHW), non-Hispanic Black, Hispanic, and the 7 largest Asian American populations. We calculated the differential incidence between non-White groups and NHW using incidence rate ratios and 95% confidence intervals (CIs). Compared with NHW subjects, all non-White groups had significantly higher incidences of noncardia gastric adenocarcinoma; the incidence was highest among Korean American men 50 years and older (70 cases per 100,000). Compared with NHW subjects 50 years and older, the risk of noncardia gastric adenocarcinoma was 1.8-fold (95% CI, 1.37-2.31) to 7.3-fold (95% CI, 5.73-9.19) higher in most non-White groups and 12.0-fold (95% CI, 9.96-14.6) to 14.5-fold (95% CI, 12.5-16.9) higher among Korean American men and women 50 years and older, respectively. Compared with NHW men 50 years and older, all non-White men, except Japanese and Korean American men, had a significantly lower risk of cardia gastric adenocarcinoma. We identified several-fold differences in incidences of gastric adenocarcinoma in specific anatomic sites among racial and ethnic groups, with significant age and sex differences. These findings can be used to develop targeted risk reduction programs for gastric adenocarcinoma.

Abstract PR03: Disaggregation of gastric cancer risk Between Asian American subgroups

Abstract Introduction: Within the United States (US), Asian/Pacific Islanders (APIs) are at increased risk for non-cardia gastric adenocarcinoma (NCGA) compared to non-Hispanic whites (NHWs). Previous epidemiologic research has treated APIs as an aggregated group for analysis; however, substantial genetic and environmental differences may exist within subgroups. Very limited data exist regarding gastric cancer epidemiology as stratified by API subgroup. Methods: All incident cases of NCGA diagnosed in the years 2000-2014 were identified from the Surveillance, Epidemiology, and End Results Program registries incorporating California, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Atlanta, and New Jersey. API subgroup of patients was identified: Korean, Japanese, Chinese, Vietnamese, Filipino, and Indian. API subgroup population estimates were obtained from the American Community Survey. The age-adjusted incidence rates per 100,000 population and 95% confidence intervals (CIs) were generated for each subgroup, and among non-Hispanic whites (NHWs) for reference. The stages of diagnosis (as defined by National Cancer Institute summary stage) were compared between subgroups. Differences between subgroups in all-cause mortality following diagnosis were evaluated utilizing proportional hazards (PH) regression, adjusting for differences in tumor stage, age, and gender. Results: There exist substantial differences in age-adjusted incidences of NCGA between subgroups: Koreans (34.8 per 100K), Japanese (17.0 per 100K), Vietnamese (14.6 per 100K), Chinese (11.2 per 100K), Indian (5.4 per 100K), and Filipino (5.3 per 100K). The incidence among NHWs was 3.8 per 100K. All API subgroups as well as NHWs demonstrated a decrease in age-standardized incidence over the study period. There exist differences in the proportion of cancers diagnosed at local stage: Koreans (37.8%), Japanese (28.1%), Chinese (25.7%), Vietnamese (24.4%), Indian (21.6%), Filipino (18.9%), and NHWs (23.7%). API subgroups had better overall survival from NCGA compared to NHWs (reference) in PH regression: Korean (HR 0.50, CI 0.47-0.54, p&amp;lt;0.001), Japanese (HR 0.79, CI 0.74-0.85, p&amp;lt;0.001), Vietnamese (HR 0.79, CI 0.72-0.87, p&amp;lt;0.001), Chinese (HR 0.70, CI 0.65-0.74, p&amp;lt;0.001), and Indian (HR 0.69, CI 0.58-0.81, p&amp;lt;0.001). These differences remained significant even after adjustment for stage of diagnosis, age, and gender. Discussion: Substantial heterogeneity in risk for NCGA exist between API subgroups. Korean Americans are at highest risk, with incidence nearly seven-fold higher than Filipinos and Indians (whose risk is similar to NHW). This suggests that the higher NCGA-risk in APIs in aggregate are driven by certain subgroups. Interestingly, Koreans, Japanese, Vietnamese, Chinese, and Indians all had better survival following NCGA diagnosis than NHWs, even after adjustment for stage of diagnosis. These epidemiologic data may hold important implications for gastric cancer screening or surveillance programs. This abstract is also being presented as Poster B104. Citation Format: Robert J. Huang, Joo Ha Hwang, Ann Hsing, Latha Palaniappan. Disaggregation of gastric cancer risk Between Asian American subgroups [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr PR03.

Helicobacter pylori Is Associated With Precancerous and Cancerous Lesions of the Gastric Cardia Mucosa: Results of a Large Population-Based Study in China.

Background: Helicobacter pylori (H. pylori) is widely accepted to be the most important cause of gastric non-cardia adenocarcinoma (GNCA), while its role in the development of gastric cardia adenocarcinoma (GCA) is not well-defined. We aimed to investigate current H. pylori infection in relation to the severity of both precancerous and cancerous lesions of the gastric cardia in an Asian population at high risk of GCA.Methods: A population-based cross-sectional study was conducted in Linzhou County, Henan Province, China. Two thousand three (2,003) randomly selected participants with data on current H. pylori infection, assayed by 13C-urea breath test (13C-UBT), and a sequence of histological diagnoses of the gastric cardia mucosa were analyzed.Results: Of 2,003 subjects, 828 (41.33%) were currently infected with H. pylori. The prevalence of current H. pylori infection increased with increasing severity of histological lesions, from 34.12% in subjects with normal gastric cardia mucosa to 52.17% in subjects with gastric cardia high-grade intraepithelial neoplasia (CHIN)/ gastric cardia adenocarcinoma (GCA) (P for trend <0.001). With H. pylori-negative subjects as the reference category, H. pylori-positive subjects had statistically significant elevated adjusted prevalence odds ratios (PORs) for each of the histological lesions. The PORs (95% CI) were 2.15 (1.74–2.64), 3.46 (2.08–5.75), 2.78 (1.90–4.07), and 3.05 (1.30–7.17) for subjects with carditis, cardia intestinal metaplasia (CIM), cardia low-grade intraepithelial neoplasia (CLIN), and CHIN/GCA), respectively. The associations remained when subjects with abnormal stomach non-cardia mucosa were excluded.Conclusions: This large epidemiologic study demonstrates a positive association between current H. pylori infection and the severity of both precancerous and cancerous lesions of the gastric cardia in an Asian population at high risk of GCA. These findings suggest that H. pylori infection may play a role throughout both early- and late-stage development of GCA.

Presence of cagPAI genes and characterization of vacA s, i and m regions in Helicobacter pylori isolated from Alaskans and their association with clinical pathologies.

Introduction. Gastric cancer is a health disparity in the Alaska Native people. The incidence of Helicobacter pylori infection, a risk factor for non-cardia gastric adenocarcinoma, is also high. Gastric cancer is partially associated with the virulence of the infecting strain.Aim. To genotype the vacA s, m and i and cag pathogenicity island (cagPAI) genes in H. pylori from Alaskans and investigate associations with gastropathy.Methodology. We enrolled patients with gastritis, peptic ulcer disease (PUD) and intestinal metaplasia (IM) in 1998-2005 and patients with gastric cancer in 2011-2013. Gastric biopsies were collected and cultured and PCR was performed to detect the presence of the right and left ends of the cagPAI, the cagA, cagE, cagT and virD4 genes and to genotype the vacA s, m and i regions.Results. We recruited 263 people; 22 (8 %) had no/mild gastritis, 121 (46 %) had moderate gastritis, 40 (15%) had severe gastritis, 38 (14 %) had PUD, 30 (11 %) had IM and 12 (5 %) had gastric cancer. H. pylori isolates from 150 (57%) people had an intact cagPAI; those were associated with a more severe gastropathy (P≤0.02 for all comparisons). H. pylori isolates from 77 % of people had either the vacA s1/i1/m1 (40 %; 94/234) or s2/i2/m2 (37 %; 86/234) genotype. vacA s1/i1/m1 was associated with a more severe gastropathy (P≤0.03 for all comparisons).Conclusions. In this population with high rates of gastric cancer, we found that just over half of the H. pylori contained an intact cagPAI and 40 % had the vacA s1/i1/m1 genotype. Infection with these strains was associated with a more severe gastropathy.

How to Manage a Patient With Gastric Intestinal Metaplasia: An International Perspective

How to Manage a Patient With Gastric Intestinal Metaplasia: An International Perspective

Contrasting Prognostic Effects of Tumor-Infiltrating Lymphocyte Density in Cardia and Non-cardia Gastric Adenocarcinomas.

PurposeThis study sought to investigate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in relation to tumor location within the stomach.Materials and MethodsThe densities and prognostic significance of TIL subsets were evaluated in 542 gastric cancer patients who underwent gastrectomy. Immunohistochemical staining for CD3, CD4, CD8, forkhead/winged helix transcription factor (Foxp3), and granzyme B was performed.ResultsCardia cancer was associated with significantly lower densities of CD8 T-cells and higher densities of Foxp3 and granzyme B T-cells than non-cardia tumors. Multivariate analysis showed that advanced age (hazard ratio [HR], 1.023; 95% confidence interval [CI], 1.006–1.040), advanced T classification (HR, 2.029; 95% CI, 1.106–3.721), lymph node metastasis (HR, 3.319; 95% CI, 1.947–5.658), low CD3 expression (HR, 0.997; 95% CI, 0.994–0.999), and a high Foxp3/CD4 ratio (HR, 1.007; 95% CI, 1.001–1.012) were independent predictors of poor overall survival in cardia cancer patients. In non-cardia cancer patients, total gastrectomy (HR, 2.147; 95% CI, 1.507–3.059), advanced T classification (HR, 2.158; 95% CI, 1.425–3.266), lymph node metastasis (HR, 1.854; 95% CI, 1.250–2.750), and a low Foxp3/CD4 ratio (HR, 0.978; 95% CI, 0.959–0.997) were poor prognostic factors for survival.ConclusionsThe densities and prognostic effects of TILs differed in relation to the location of tumors within the stomach. The contrasting prognostic effects of Foxp3/CD4 ratio in cardia and non-cardia gastric cancer patients suggests that clinicians ought to consider tumor location when determining treatment strategies.

Serologic Profile of Antiparietal Cell Antibodies, Pepsinogens, and H. pylori and Risk of Upper Gastrointestinal Cancer: A Nested Case-Control Study in China.

Autoimmune gastritis is understudied and possibly associated with gastric noncardia adenocarcinoma (GNCA) and esophageal squamous cell carcinoma (ESCC) in Western populations when it presents as pernicious anemia. A nested case-control study within a Chinese cohort included 100 ESCC, 200 gastric cardia adenocarcinoma (GCA), and 200 GNCA cases diagnosed between 1986 and 2001 and 400 controls. Serostatus of antiparietal cell antibodies (APCA), Helicobacter pylori antibodies, and pepsinogens were measured using commercial kits and serum collected at baseline. We used logistic regression to calculate odds ratios (OR) and 95% confidence interval (CI) for associations between serologic biomarkers and cancer risk adjusted for numerous potential confounders. There was an average interval of 8 years between baseline blood draw and cancer diagnosis. The baseline prevalence of APCA seropositivity was 10.0% and 14.5% in subjects who developed GCA and GNCA, respectively. APCA seropositivity was inversely associated with later development of GCA (OR = 0.42; 95% CI, 0.24-0.75), but not significantly associated with later development of GNCA (OR = 0.82; 95% CI, 0.50-1.36) or ESCC (OR = 1.05; 95% CI, 0.58-1.88). APCA seropositivity was significantly associated with low pepsinogen I/II ratios (OR = 3.69; 95% CI, 1.66-8.21), and individuals with low pepsinogen I/II ratios who were seronegative for APCA had the highest risk of both GCA and GNCA. APCA seropositivity measured years prior to diagnosis was associated with prevalent atrophic gastritis but inversely associated with incident GCA in this Chinese population. APCA may contribute to a growing list of serologic markers that can improve risk stratification for gastric cancer.

Prevalence of Helicobacter pylori Positive Non-cardia Gastric Adenocarcinoma Is Low and Decreasing in a US Population.

Helicobacter pylori infection is an established causal factor for non-cardia gastric cancer. H. pylori negative gastric cancer prevalence among US patients is unclear. This retrospective cohort study examined H. pylori prevalence among consecutive patients with incident non-cardia gastric adenocarcinoma at the Houston VA Hospital (11/2007-10/2018). H. pylori positivity was defined by H. pylori on histopathology, positive antibody serology, stool antigen, or urea breath testing. We examined for trends in H. pylori negative gastric cancer based on year of diagnosis. Associations between histopathologic and cancer-related outcomes with H. pylori positivity were determined using regression models. Of 91 patients with gastric adenocarcinoma, most were men (N = 87, 95.6%), black (N = 47, 51.6%), with mean age at diagnosis of 68.0years (SD 10.8). In addition to gastric cancer biopsy histopathology, 74 patients (81.3%) had ≥ 1 testing for H. pylori, including antibody serology (n = 34), non-cancer gastric biopsy histopathology (n = 63), or stool antigen (n = 1). The overall prevalence of H. pylori infection was 38.5% and 45.9% among patients with ≥ 2 H. pylori tests. The proportions of H. pylori positive gastric cancer decreased from 50.0% (2007-2010) to 43.4% (2011-2014) and 29.3% (2015-2018) (p = 0.096). Active/acute gastritis (adjOR 3.74), atrophic gastritis (adjOR 15.30), and gastric intestinal metaplasia (adjOR 3.65) were associated with H. pylori positive gastric cancer. The prevalence of H. pylori infection among patients with non-cardia gastric adenocarcinoma is relatively low (38.5-45.9%) and decreasing over time. This finding suggests there may be other important causal factors apart from H. pylori for gastric adenocarcinoma.

Associations between calcium and magnesium intake and the risk of incident gastric cancer: A prospective cohort analysis of the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study.

Gastric cancer remains a leading cause of cancer-related mortality. Identifying dietary and other modifiable disease determinants has important implications for risk attenuation in susceptible individuals. Our primary aim was to estimate the association between dietary and supplemental intakes of calcium and magnesium and the risk of incident gastric cancer. We conducted a prospective cohort analysis of the National Institutes of Health-American Association of Retired Persons Diet and Health Study. We used Cox proportional hazard modeling to estimate the association between calcium and magnesium intakes with risk of incident gastric adenocarcinoma (GA) overall and by anatomic location, noncardia GA (NCGA) and cardia GA (CGA). A total of 536,403 respondents (59% males, 41% females) were included for analysis, among whom 1,518 incident GAs (797 NCGA and 721 CGA) occurred. Increasing calcium intake was associated with lower risk of GA overall (p-trend = 0.05), driven primarily by the association with NCGA, where the above median calcium intakes were associated with a 23% reduction in risk compared to the lowest quartile (p-trend = 0.05). This magnitude of NCGA risk reduction was greater among nonwhite ethnic group and Hispanics (hazard ratio [HR] 0.51, 95% confidence interval [CI]: 0.24-1.07, p-trend = 0.04), current/former smokers (HR 0.58, 95% CI: 0.41-0.81), obese individuals (HR 0.54, 95% CI: 0.31-0.96) and those with high NCGA risk scores (HR 0.50, 95% CI: 0.31-0.80). Among men only, increasing magnesium intake was associated with 22-27% reduced risk of NCGA (p-trend = 0.05), while for the cohort, dietary magnesium intake in the highest vs. lowest quartile was associated with a 34% reduced risk of NCGA (HR 0.66, 95% CI: 0.48-0.90). These findings have important implications for risk factor modification. Future investigations are needed not only to confirm our results, but to define mechanisms underlying these associations.

Metformin use and risk of gastric adenocarcinoma in a Swedish population-based cohort study

BackgroundWhether or not the use of metformin decreases the risk of gastric adenocarcinoma is unclear.MethodsThis was a population-based cohort study in 2005–2015. Associations between metformin use and gastric non-cardia and cardia adenocarcinomas were examined within two cohorts; a diabetes cohort of participants using anti-diabetes medications, and a matched cohort of common-medication users, where metformin non-users were frequency matched (10:1) with metformin users for sex and age. Multivariable Cox proportional hazard regression analyses provided hazard ratios (HR) and 95% confidence intervals (CI), adjusting for sex, age, calendar year, comorbidity, Helicobacter pylori eradication treatment, use of non-steroidal anti-inflammatory drugs or aspirin and use of statins.ResultsDuring the follow-up for a median of 5.8 years, 892 (0.1%) participants in the diabetes cohort and 6395 (0.1%) participants in the matched cohort of common-medication users developed gastric adenocarcinoma. Metformin users had no significantly decreased risk of gastric non-cardia adenocarcinoma (diabetes cohort: HR 0.93, 95% CI 0.78–1.12; matched cohort: HR 1.30, 95% CI 1.18–1.42) or cardia adenocarcinoma (diabetes cohort: HR 1.49, 95% CI 1.09–2.02; matched cohort: HR 1.58, 95% CI 1.38–1.81) compared with non-users in both cohorts.ConclusionsThis cohort study with <10 years of follow-up suggests metformin use may not prevent gastric adenocarcinoma.

Risk factors predisposing to cardia gastric adenocarcinoma: Insights and new perspectives.

Recent decades have seen an alarming increase in the incidence of cardia gastric adenocarcinoma (CGA) while noncardia gastric adenocarcinoma (NCGA) has decreased. In 2012, 260 000 CGA cases (age‐standardised rate (ASR); 3.3/100 000) and 691 000 NCGA cases (ASR; 8.8/100 000) were reported worldwide. Compared with women, men had greater rates for both the subsites, especially for CGA. Recently, four molecular subtypes of GC have been proposed by the Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG); however, these classifications do not take into account predisposing germline variants and their possible interaction with somatic alterations in carcinogenesis. The etiology of adenocarcinoma of the cardia and the gastroesophageal junction (GEJ) is not known. It is thought that CGA is distinct from adenocarcinomas located in the esophagus or distal stomach, both epidemiologically and biologically. Moreover, CGA is often identified in the advanced stage having a poor prognosis. Therefore, understanding the risk and the role of predisposing factors in etiology of CGA can inform clinical practice and counseling for risk reduction. In this paper, we showed that GC family history, lifestyle, demographics, gastroesophageal reflux disease, Helicobacter pylori infection, and multiple genetic and epigenetic risk factors as well as several predisposing conditions may underlie susceptibility to CGA. However, several genome‐wide association studies (GWASs) should be conducted to identify novel high‐penetrance genes and pathways as well as causal germline variants predisposing to CGA. They must include different ethnic groups, especially from high‐incidence countries for CGA, because some risk loci are ancestry‐specific. In parallel, statistical methods can be developed to identify cancer predisposition genes (CPGs) from tumor sequencing data. It is also necessary to find novel long noncoding RNAs related to the risk of CGA. Taken altogether, new cancer risk prediction models, including all genetic and nongenetic factors influencing risk, should be developed to facilitate risk assessment, disease prevention, and early diagnosis and intervention of CGA in the future.

Serum ghrelin and esophageal and gastric cancer in two cohorts in China.

Ghrelin is a hormone produced in the oxyntic glands of the stomach. Previous work by our group has suggested that serum ghrelin concentrations are inversely associated with gastric and esophageal cancer risk. We measured ghrelin concentrations in the Linxian General Population Nutrition Intervention Trial (NIT), and the Shanghai Women's Health Study (SWHS). In NIT, we analyzed serum samples from 298 esophageal squamous cell carcinoma (ESCC) cases, 518 gastric cardia adenocarcinoma (GCA) cases, 258 gastric noncardia adenocarcinoma (GNCA) cases and 770 subcohort controls (case-cohort). In SWHS, we measured ghrelin in plasma samples from 249 GNCA cases and 498 matched controls (nested case-control). Ghrelin was measured using radioimmunoassay. In NIT and SWHS, low ghrelin concentrations were associated with an increased risk of developing GNCA and GCA. The hazard ratio (HR Q1:Q4 ) for GNCA in NIT was 1.35 (95% CI: 0.89-2.05; p-trend = 0.02); the odds ratio in SWHS was 1.66 (95% CI: 1.02-2.70; p-trend = 0.06). Low ghrelin was associated with a twofold increase of GCA (HR Q1:Q4 = 2.00, 95% CI: 1.45-2.77; p-trend<0.001). In contrast, a lower risk of ESCC (NIT ESCC HR Q1:Q4 = 0.65, 95% CI: 0.45-0.92; p-trend = 0.02) was found in NIT. Low baseline ghrelin concentrations were associated with an increased risk for GNCA and GCA in the NIT and the SWHS. In contrast, low ghrelin concentrations at baseline were associated with a reduced risk of developing ESCC in the NIT. Ghrelin may be an early marker of future cancer risk for developing upper gastrointestinal cancer in regions of high incidence.