Non-cardia Adenocarcinoma Research Articles

Adherence to the Mediterranean Diet and Risk of Gastric Cancer: A Systematic Review and Meta-Analysis.

Available results on the association between the Mediterranean diet (MD) and gastric cancer (GC) incidence are controversial. The present study aimed to determine the correlation between different subtypes of GC and MD adherence. This meta-analysis was registered on PROSPERO (CRD42021284432). We searched Embase, PubMed, Cochrane Library, and Web of Science from inception through 22 April 2023 to retrieve relevant studies. A random-effects model was used to pool odds ratios (ORs) with 95% confidence intervals (CIs). Eleven studies were included in the meta-analysis. Pooled analyses revealed that adherence to the MD was inversely associated with GC risk (ORcc, 0.43; 95% CI, 0.29 to 0.63; ORcoh, 0.84; 95% CI, 0.77 to 0.92). Higher MD adherence was significantly associated with a reduced GC risk in male (ORcc, 0.78; 95% CI, 0.65 to 0.93; ORcoh, 0.81; 95% CI, 0.65 to 1.01), but not in female (ORcc, 0.83; 95% CI, 0.68 to 1.01; ORcoh, 1.04; 95% CI, 0.82 to 1.31). Furthermore, adherence to the MD possibly decreased the risk of gastric cardia adenocarcinoma (GCA) (ORcc, 0.64; 95% CI, 0.49 to 0.83; ORcoh, 0.88; 95% CI, 0.76 to 1.02) and gastric non-cardia adenocarcinoma (GNCA) (ORcc, 0.68; 95% CI, 0.59 to 0.79; ORcoh, 0.85; 95% CI, 0.78 to 0.94). Our results indicate that adherence to the MD reduces the risk of GC and its subtypes.

Recent incidence trends of oesophago-gastric cancer in Sweden

Background Oesophago-gastric cancers have had sharply different and changing incidence patterns depending on subsite and histology, but incidence data for the last few years are missing. We aimed to provide updated incidence trends of oesophago-gastric tumours by subsite and histology in Sweden. Material and Methods The Swedish Cancer Registry provided data for 74,303 patients with oesophago-gastric cancer aged ≥50 years in 1970–2020. The focus was on the last available 6-year period, i.e., from 2015 until 2020 inclusive. We calculated yearly age-standardized and sex-specific incidence rates per 100,000 person-years, with the age distribution (in 5-year age groups) of the Swedish population in year 2000 as reference. Results For oesophageal squamous cell carcinoma, the incidence continued to decrease between 2015 and 2020 (from 6.46 to 5.53/100,000 person-years in men, and from 4.26 to 3.78/100,000 person-years in women). For oesophageal adenocarcinoma, the earlier increasing incidence rates rather slightly decreased in men between 2015 and 2020 (from 12.39 to 11.70/100,000 person-years) and increased marginally in women (from 2.49 to 2.85/100,000 person-years). The incidence rates of cardia adenocarcinoma were stable between 2015 and 2020 (from 9.83 to 10.13/100,000 person-years in men, and from 2.21 to 2.41/100,000 person-years in women). For gastric non-cardia adenocarcinoma, the incidence rates continued to decrease between 2015 and 2020 (from 14.67 to 13.29/100,000 person-years in men, and from 9.37 to 8.14/100,000 person-years in women). There were no major age-group differences in recent incidence trends. Conclusion The 6-year period from 2015 to 2020 inclusive has witnessed stabilising incidence rates of oesophageal and cardia adenocarcinoma in Sweden, whereas the incidence rates of oesophageal squamous cell carcinoma and non-cardia gastric adenocarcinoma have continued to decrease.

The impact of a healthy lifestyle on the risk of esophageal and gastric cancer subtypes

Few prospective studies have been conducted on a combined healthy lifestyle and risk of esophageal and gastric cancer, and even less on subtypes: esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA). The relationship of a healthy lifestyle score (HLS) with risk of these cancers was investigated in the Netherlands Cohort Study. In 1986, 120,852 men and women aged 55–69 years provided information on dietary and lifestyle habits. The HLS was derived from information on smoking, body mass index, physical activity, Mediterranean diet adherence, and alcohol intake. After 20.3 years of follow-up, multivariable case-cohort analyses were based on 333 incident esophageal and 777 gastric cancer cases, and 3720 subcohort members with complete data on lifestyles and confounders. The impact of changing to healthy lifestyles was estimated with the rate advancement period (RAP). The HLS was significantly inversely associated with risk of esophageal and gastric cancer, and subtypes (except EAC), in a linear fashion. The observed HR decrease per 1-point increase in HLS was 31% for esophageal, and 19% for gastric cancer, 49% for ESCC, 23% for GCA, and 18% for GNCA. The RAP per 1-point increase in HLS ranged from − 11.75 years for ESCC to − 2.85 years for GNCA. Also after excluding smoking, inverse associations between the HLS and esophageal and gastric cancer risk were still apparent. These results suggest that adhering to a combination of healthy modifiable lifestyle factors may substantially reduce the risk of esophageal and gastric cancer.

Survival trends in gastric cancer patients between 1987 and 2016: a population-based cohort study in Finland

BackgroundGastric cancer is the fourth leading cause of cancer-related deaths globally. There is a paucity of national studies examining gastric cancer mortality in relation to treatment status. This study evaluated the survival trends in gastric adenocarcinoma and all gastric cancers stratified by treatment in Finland during 1987–2016.MethodsThis population-based, nationwide, retrospective cohort study included all gastric cancer patients registered in the Finnish Cancer Registry and Patient Registry. The survival rates were calculated for 1, 3, and 5 years, stratified by treatment. Prognostic factors were determined using Cox regression.ResultsA total of 18,713 non-cardia gastric adenocarcinoma, and 3617 cardia adenocarcinoma patients were included. Surgical treatment decreased for non-cardia adenocarcinoma and remained constant for cardia adenocarcinoma. In non-cardia adenocarcinoma, the 5-year survival declined from 17% to 16% from 1987–1991 to 2012–2016. In surgically treated patients, survival increased from 29% to 38%, while an increase from 4% to 7% in those undergoing chemotherapy and decrease from 6% to 3% in those not receiving any treatment were observed. In cardia adenocarcinoma, the 5-year survival increased from 10% to 18% in all patients, 16% to 40% in surgical patients, 0% to 5% in patients receiving chemotherapy, and from 5% to 9% in patients receiving no treatment. Earlier calendar periods, older age, male sex, and higher comorbidity were risk factors for poor prognosis.ConclusionsGastric non-cardia adenocarcinoma survival declined, limited to advanced stage patients not receiving any treatment. Gastric cardia cancer survival seems to have improved over time in Finland.Mini abstractThis study evaluated survival trends of gastric cancer in Finland during 1987–2016 and established that the 5-year survival is declining in non-cardia adenocarcinoma but improving in all gastric cancers.

Use of anti-androgenic 5α-reductase inhibitors and risk of oesophageal and gastric cancer by histological type and anatomical sub-site

BackgroundTo investigate if anti-androgenic medications 5α-reductase inhibitors (5-ARIs) decrease the risk of developing oesophageal and gastric tumours, analysed by histological type and anatomical sub-site.MethodsA Swedish population-based cohort study between 2005 and 2018 where men using 5-ARIs were considered exposed. For each exposed participant, ten male age-matched non-users of 5-ARIs (non-exposed) were included. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, smoking, non-steroidal anti-inflammatory drugs/aspirin use, and statins use. Further adjustments were made depending on the tumour analysed.ResultsThe cohort included 191,156 users of 5-ARIs and 1,911,560 non-users. Overall, the use of 5-ARIs was not associated with any statistically significantly reduced risk of oesophageal or cardia adenocarcinoma (adjusted HR 0.92, 95% CI 0.82–1.02) or gastric non-cardia adenocarcinoma (adjusted HR 0.90, 95% CI 0.80–1.02). However, the use of 5-ARIs indicated a decreased risk of oesophageal or cardia adenocarcinoma among obese or diabetic participants (adjusted HR 0.55, 95% CI 0.39–0.80) and a reduced risk of oesophageal squamous cell carcinoma (adjusted HR 0.49, 95% CI 0.37–0.65).ConclusionUsers of 5-ARIs may have a decreased risk of developing oesophageal or cardia adenocarcinoma among those obese or diabetic, and a decreased risk of oesophageal squamous cell carcinoma.

Abstract 737: Diet quality and risk of gastric adenocarcinoma: The Multiethnic Cohort

Abstract Background: Certain diet components (i.e. low intake of fruit/vegetables and high intake of salt and processed meats) have been associated with risk of gastric cancer. However, it is unclear whether overall diet quality assessed by pre-defined indices, that take into account the complexity of dietary intake, is associated with gastric cardia and distal adenocarcinoma particularly in a racially and ethnically diverse population. Our objectives are to 1) examine the association of a variety of diet quality indices with risk of gastric cardia and distal adenocarcinoma and 2) assess if there are any subgroups that may benefit from better diets to reduce risk of gastric adenocarcinoma. Methods: The analysis included 176,752 men and women aged 45-75 from the Multiethnic Cohort (MEC), who were African American, Japanese American, Latino, Native Hawaiian, or White, and completed a quantitative food frequency questionnaire (QFFQ) at cohort entry. Incident cases of gastric cancer (cardia ICD-O-3 C16.0 and non-cardia adenocarcinoma C16.1-C16.6) were identified by linkages with the Surveillance, Epidemiology, and End Results (SEER) cancer registries. Dietary indices, Alternative Healthy Index-2010 (AHEI-2010), Healthy Eating Index-2015 (HEI-2015), Dietary Approach to Stop Hypertension (DASH) score, alternate Mediterranean Diet (aMED) score, and Dietary Inflammatory Index (DII®), were calculated from the QFFQ and categorized into quintiles. Multivariable Cox models were used to estimate the association between dietary indices and gastric cancer risk by anatomic site. Effect modification was assessed for distal cancer by sex, smoking status, and aspirin use. Results: A total of 207 incident cases of gastric cardia and 836 incident cases of gastric non-cardia were identified during an average follow up of 19.2 years. We did not observe any significant associations between any of the dietary indices and gastric cancer for both cardia and non-cardia tumors. However, we observed effect modification by aspirin use for aMED (P for heterogeneity = 0.01) as well as for DII (P for heterogeneity = 0.02). Among ever aspirin users, we observed an inverse association between aMED (HRQ5 vs Q1: 0.82, 95% CI: 0.53-1.26, Ptrend = 0.03) with non-cardia cancer, and the association with DII® was borderline statistically significant for the trend test (HRQ5 vs Q1: 0.86, 95% CI: 0.57-1.29, Ptrend = 0.07). Conclusion: In a multiethnic population, we did not observe overall significant associations between these dietary quality indices and risk of gastric cancer. However, among ever aspirin users there could be a reduction of gastric non-cardia adenocarcinoma risk with a higher adherence to a Mediterranean diet. Citation Format: Nicholas Acuna, Song-Yi Park, Anna H. Wu, Lynne R. Wilkens, V. Wendy Setiawan. Diet quality and risk of gastric adenocarcinoma: The Multiethnic Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 737.

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.

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.

Trefoil factor 1 and gastrokine 2 inhibit Helicobacter pylori-induced proliferation and inflammation in gastric cardia and distal carcinogenesis.

Helicobacter pylori (H. pylori) infection has been associated with non-cardia adenocarcinoma in the stomach, while its role in gastric cardia adenocarcinoma (GCA) remains controversial. In addition, the association between H. pylori and the protective factors trefoil factor 1 (TFF1) and gastrokine 2 (GKN2) in gastroesophageal adenocarcinomas has not been fully investigated. Therefore, the mRNA and protein expression levels of TFF1 and GKN2 in GCA and distal gastric adenocarcinoma (DGA) were analyzed using quantitative PCR (qPCR) and immunohistochemistry, and the association with H. pylori infection was investigated. In addition, the effects of TFF1 and GKN2 overexpression on H. pylori-induced cells were investigated using western blot and reverse transcription-qPCR analysis. The comparative analysis of 16S rRNA-positive mRNA expression between GCA and DGA showed no statistically significant difference. However, the rate of the H. pylori vacuolating toxin A (VacA) genotype was significantly higher in GCA (49.2%) compared with that in DGA (26.9%; P<0.05). H. pylori infection downregulated the mRNA and protein expression levels of TFF1 and GKN2 in gastric tumor tissues, and the mRNA expression level of TFF1 and GKN2 was also markedly decreased in vitro. Furthermore, the cell proliferation varied in H. pylori total protein treatment group with the different doses. Notably, treatment with 20 µg/ml H. pylori total protein for 24 h resulted in the highest cellular proliferation rate. In addition, TFF1 and GKN2 overexpression inversely inhibited H. pylori-induced cell proliferation and upregulated NF-κB, tumor necrosis factor-α, IL-1β, IL-2, IL-4 and IL-6. The results of the present study indicate that H. pylori, particularly the VacA+ strain, plays an important role in GCA pathogenesis in high-risk areas of China, while TFF1/GKN2 inhibits H. pylori-induced cell proliferation and inflammation in GCA and DGA.

Changing Disparity of Gastric Cancer Incidence by Histological Types in US Race-Specific Populations.

Background:The incidence pattern of gastric cancer by histological types across major race/ethnic groups is unknown.Methods:Age-standardized rates from 1992-2016 by race/ethnicity were calculated using data from Surveillance, Epidemiology, and End Results Program (SEER). Annual percent changes (APCs) in rates and corresponding 95% confidence intervals (CIs) were calculated and pairwise comparison of rates between race/ethnic groups was performed using the Joinpoint Regression Program. Calendar periods of incidence rates of gastric cardia and non-cardia cancer by histological types across race/ethnicity groups were shown by figures.Results:The White population has the highest incidence of gastric cardia adenocarcinoma and the incidence is keeping constant from 1992 through 2016 except the decreasing in the Asian population (AAPC = −1.4, 95%CI (−2.1, −0.8)). Although the incidence of non-cardia adenocarcinoma is decreasing in each group, the descending trend in the Asian population is the quickest (AAPC = −3.8, 95%CI (−4.0, −3.5)). Gastric carcinoids were observed to have statistically significant increasing trends in all race/ethnicity groups, especially in Hispanic women from 0.4 per 100,000 to 1.6 per 100,000 persons. The incidence of gastrointestinal stromal tumors (GISTs) is rising, with Non-Hispanic blacks having the highest incidence.Conclusion:This study demonstrated disparities in the incidence of gastric cancer by histological types among different race/ethnic groups. Further investigations are warranted to understand the changing incidence patterns by race/ethnicity.

Causes of death in patients diagnosed with gastric adenocarcinoma in Sweden, 1970-2014: A population-based study.

The causes of death in patients with gastric adenocarcinoma have not been well characterized. This nationwide population‐based cohort study included 56 240 patients diagnosed with gastric adenocarcinoma in 1970‐2014 in Sweden. We used competing‐risks regression to compare cause‐specific risks of death in patients with different characteristics and a multiple‐cause approach to assess proportions of deaths attributable to each cause. Among 53 049 deaths, gastric cancer was the main (77.7% of all deaths) underlying cause. Other major underlying causes were nongastric malignancies (8.0%), ischemic heart disease or cerebrovascular disease (6.5%), and respiratory diseases (1.4%). Risk of death from gastric cancer steadily decreased in patients with cardia adenocarcinoma over the study period, but remained relatively stable in patients with noncardia adenocarcinoma since the 1980s. Risk of death from other malignancies increased during later calendar periods (subhazard ratio [SHR] = 2.16, 95% confidence interval [CI] 1.97‐2.38, comparing 2001‐2014 with 1970‐1980). Compared with men, the risk of death in women with cardia adenocarcinoma was higher from gastric cancer (SHR = 1.18, 95% CI 1.10‐1.27), but lower from other malignancies (SHR = 0.80, 95% CI 0.71‐0.91). In multiple‐cause models, 60.4%‐71.2% of all deaths were attributable to gastric cancer and 9.5%‐12.1% to other malignancies. The temporal trends of cause‐specific risks from multiple‐cause models were similar to those of underlying causes. Our findings suggest that although most deaths in patients with gastric adenocarcinoma are due to gastric cancer, other causes of death are common. Patients with cardia adenocarcinoma face considerable increasing risk of death from other causes over time, particularly from other malignancies.

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.

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.

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.

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.

PLCE1 Polymorphisms and Risk of Esophageal and Gastric Cancer in a Northwestern Chinese Population.

The reported risk susceptibility between phospholipase C epsilon 1 (PLCE1) polymorphisms and esophageal cancer (EC) and gastric cancer (GC) remained inconsistent and controversial, especially on variants other than rs2274223. The relationship between PLCE1 polymorphisms and gene expression is also unclear. Here we conducted a case-control study from northwest China, genotyped seven tag single nucleotide polymorphisms (SNPs) in PLCE1 with multiplexed SNP MassARRAY assay. Stratified analysis was carried out and PLCE1 expression was evaluated in specified groups with the method of qRT-PCR and immunohistochemistry. Results showed that the minor alleles of rs3765524, rs2274223, and rs10509670 were associated with increased risk of EC and GC. Linkage disequilibrium analysis revealed protective haplotypes of CCAAGTC and CCAA. By stratification, a more significant association was found in subgroups of male, age ≥ 54, tumor stages of I-II and tumor size ≤ 5 cm, EC and cardia cancer (CC) of stomach, and moderate to well differentiated squamous carcinoma. In addition, a significant association for rs3765524 with noncardia cancer (NCC) and adenocarcinoma which is predominant in China was also observed. Further expression analysis identified that PLCE1 was downregulated in NCC tissues comparing to their adjacent noncancerous tissues, and its protein expression was higher in genotype rs3765524 CT/TT than in rs3765524 CC. In summary, our study suggests that PLCE1 polymorphisms may affect its gene expression and are associated with not only EC and CC, but also, to some extent, NCC risk in this study population.

Mediterranean diet adherence and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study

BackgroundMediterranean diet (MD) adherence has been associated with reduced risks of esophageal and gastric cancer (subtypes) in a limited number of studies. We prospectively investigated associations between MD adherence and risks of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA) in a Dutch cohort.MethodsAnalyses were conducted using data from the 120852 participants of the Netherlands Cohort Study (NLCS), who were aged between 55 and 69 years at enrollment. Various MD scores, with and without alcohol, were calculated to estimate MD adherence. Using 20.3 years of follow-up, 133 ESCC, 200 EAC, 191 GCA, and 586 GNCA cases could be included in multivariable Cox regression analyses.ResultsOf the investigated scores, the alternate Mediterranean diet score without alcohol (aMEDr) performed best. aMEDr was inversely associated with risks of GCA and GNCA in men and women. However, statistical significance was only reached in men [ptrend: 0.019 (GCA), 0.016 (GNCA)]. Furthermore, higher aMEDr values were significantly associated with a reduced ESCC risk in men [HRper two−point increment (95% CI) = 0.57 (0.41–0.80), ptrend = 0.013], but not in women (pheterogeneity = 0.008). There was no evidence of an association between aMEDr and EAC risk. Educational level was a significant effect modifier for the association between aMEDr and GNCA risk (pheterogeneity = 0.0073).ConclusionsHigher MD adherence was associated with reduced risks of ESCC, GCA, and GNCA in the NLCS. However, the decreased ESCC risk might be limited to men.

Alcohol consumption and risk of gastric cardia adenocarcinoma and gastric noncardia adenocarcinoma: A 16‐year prospective analysis from the NIH‐AARP diet and health cohort

The role of alcoholic beverages in the etiology of gastric cancer is unclear. Recent summaries showed a positive association between higher alcohol intake and gastric cancer risk, but the magnitude of association is small, there is moderate heterogeneity among studies, and most cases were from Asian populations. We prospectively investigated the associations of alcohol consumption with gastric cardia adenocarcinoma (GCA) and gastric noncardia adenocarcinoma (GNCA) in 490,605 adults, aged 50-71 years at baseline who participated in the NIH-AARP diet and health study. Alcohol consumption in the past year was assessed at baseline by questionnaire and defined as total grams of ethanol intake per day or as a categorical variable: nondrinker, up to or including one drink per day, one to three drinks per day and greater than three drinks per day. We used multivariable-adjusted Cox proportional hazards regression to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for associations between alcohol intake and risk of gastric adenocarcinomas. Through 2011, 662 incident cases of GCA and 713 of GNCA occurred. We found no association between higher alcohol consumption and GCA or GNCA, when examined as total alcoholic beverage intake or individual beverage types of beer, wine and liquor. Furthermore, we observed no association by stratum of sex, ethnic group, educational level or smoking status. We did, however, observe lower risk of GNCA among participants who drank up to one drink per day (HR = 0.81, 95% CI: 0.67-0.97) compared to nondrinkers. In conclusion, alcohol consumption was not associated with increased risk of GCA or GNCA in this large U.S. cohort.

Survival Trends in Gastric Adenocarcinoma: A Population-Based Study in Sweden

BackgroundGastric adenocarcinoma is the second most common cancer-related death globally. Assessing survival trends can help evaluate changes in detection and treatment. We aimed to determine recent prognosis trends in gastric non-cardia and cardia adenocarcinoma in an unselected cohort with complete follow-up.MethodsPopulation-based nationwide cohort study, including 17,491 patients with gastric non-cardia adenocarcinoma and 4698 with cardia adenocarcinoma recorded in the Swedish Cancer Registry in 1990–2013 with follow-up until 2017. Observed and relative 5-year survival was calculated and stratified by resectional surgery and no such surgery. Prognostic factors were evaluated using multivariable Cox regression.ResultsThe relative overall 5-year survival remained stable at 18% for gastric non-cardia adenocarcinoma throughout the study period and increased from 12 to 18% for cardia adenocarcinoma. Concurrently, the proportion of patients who underwent resectional surgery decreased from 49 to 38% for non-cardia adenocarcinoma and from 48 to 33% for cardia adenocarcinoma. The relative postoperative 5-year survival increased from 33 to 44% for non-cardia adenocarcinoma and from 21 to 43% for cardia adenocarcinoma, whereas in nonoperated patients it decreased from 3 to 2% in non-cardia adenocarcinoma and increased from 3 to 5% in cardia adenocarcinoma. Poor prognostic factors were higher tumor stage, older age, and more comorbidity.ConclusionsDespite decreasing resectional rates, the 5-year overall survival has remained unchanged for gastric non-cardia adenocarcinoma and improved for cardia adenocarcinoma over the last two decades in Sweden and is now similar for these sublocations. The postoperative survival has improved for both sublocations, but particularly for cardia adenocarcinoma.

Intake of nuts and long-term risk of upper gastrointestinal cancer: a 30-year follow-up study in the Linxian general population trial cohort

Introduction Previous studies showed intake of nuts may affect the risk of upper gastrointestinal (UGI) cancers, but most current evidence comes from Western populations and data from Asia are limited. Cancer rates differ between countries as does nutritional status, which may lead to different associations in different populations. Therefore, we evaluated the association between intake of nuts and the risk of esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA) in a Chinese cohort. Methods In 1984, 29,584 study participants aged 40–69 completed a baseline questionnaire that included demographic characteristics, lifestyle factors and some dietary questions, including intake of nuts. The Linxian general population trial cohort was actively followed-up through 2016 to collect death endpoints from all causes of death. Adjusted hazard ratios and confidence intervals for UGI cancers by intake of nut frequency groups were estimated by using multivariate Cox regression models adjusted for age, sex, BMI, education level, tobacco smoking, and alcohol drinking. Result A total of 5470 incident UGI cancers were identified, including 3128 ESCC, 1712 GCA and 630 GNCA. Sixty-three percent of participants did not consume nuts, while 27% had nuts once per month, 8% consumed nuts 1–3 times/week, and 2% had nuts 4+ times/week. Compared to no nut consumption, no effect for any category of nut consumption was observed on risk of UGI cancers. The HRs for the highest nut consumption group (4+ times/week) compared to no nut consumption were 0.93 (95%CI: 0.72–1.21), 1.23 (95%CI: 0.86–1.76), and 1.12 (95%CI: 0.62–2.03) for risk of ESCC, GCA, and GNCA, respectively. Further, no monotonic trends were seen between level of nut consumption and risk of any specific UGI cancers. Conclusion We observed no association between intake of nuts and the risk of ESCC, GCA, or GNCA in a nutrition-deprived rural population in China.