Risk Of Gastric 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.

Esophageal abnormalities and the risk for gastroesophageal cancers—a histopathology-register-based study in Sweden

BackgroundThe poor survival of patients with gastroesophageal cancers may improve if additional esophageal precursor lesions to Barrett’s esophagus and squamous dysplasia are identified. We estimated the risk for gastroesophageal cancers among patients with various histopathological abnormalities in the esophagus, including Barrett’s esophagus, subdivided by histopathological types.MethodsHistopathology data from esophageal biopsies obtained 1979–2014 were linked with several national population-based registers in Sweden. Patients were followed from 2 years after the first biopsy date until cancer, death, emigration, esophagectomy/gastrectomy or end of follow-up, 31st of December 2016, whichever came first. We estimated standardized incidence ratios (SIRs) as measures of relative risk with the Swedish general population as reference.ResultsIn total 367 esophageal adenocarcinoma (EAC) cases were ascertained during 831,394 person-years of follow-up. The incidence rate (IR) for EAC was 0.1 per 1000 person-years for normal morphology, 0.2–0.5 for inflammatory changes, and 0.8–2.9 for metaplasia. The IR was 1.0 per 1000 person-years (95% confidence interval 0.7–1.3) among patients with non-dysplastic intestinal metaplasia, 0.9 (0.8–1.1) in non-dysplastic gastric/glandular metaplasia and 2.9 (2.0–4.2) among columnar metaplasia patients with low-grade dysplasia. The SIRs were 11.7 (95% confidence interval 8.6–15.5), 12.0 (10.0–14.2) and 30.2 (20.5–42.8), respectively. The SIRs for gastric cardia adenocarcinoma (GCA) were moderately elevated.ConclusionsFor the first time, we demonstrate that patients with esophageal inflammatory and other metaplastic abnormalities than Barrett’s esophagus have an increased risk of EAC and GCA compared to the general population. Moreover, patients with different histopathologic subtypes of Barrett’s esophagus have a comparable risk for EAC.

Surveillance of premalignant gastric cardia lesions: A population-based prospective cohort study in China.

In our study, we aimed to assess the long-term risk of gastric cardia adenocarcinoma (GCA) for patients with different histological cardia lesions to inform future guidelines for GCA screening in China. We conducted a population-based prospective study among 9740 subjects who underwent upper endoscopy screening during 2005 to 2009 and followed until December 2017. Cumulative incidence and mortality rates of GCA were calculated by the baseline histological diagnoses, and the hazard ratios (HRs), overall and by age and sex, were analyzed by Cox proportional hazards models. During a median follow-up of 10 years, we identified 123 new GCA cases (1.26%) and 31 GCA deaths (0.32%). The age-standardized incidence and mortality rates of GCA were 128.71/100 000 and 35.69/100 000 person-years, and cumulative incidence rate in patients with cardia high-grade dysplasia (CHGD), cardia low-grade dysplasia (CLGD) and atrophic carditis (AC)/cardia intestinal metaplasia (CIM) was 25%, 3.05% and 1.58%, respectively. The progression rate and cancer risk of GCA increased monotonically with each step in Correa's cascade. Individuals aged 50 to 69 years had 4.4 times higher GCA incidence than those aged 40 to 49 years. Patients with CLGD had a significantly higher 3-year GCA incidence than the normal group, while patients with AC/CIM had a comparable GCA risk during 3-year follow-up but a higher risk at 5-year intervals. Our results suggested a postponed starting age of 50 years for GCA screening, immediate treatment for patients with CHGD, a 3-year surveillance interval for patients with CLGD, and a lengthened surveillance interval of 5 years for patients with AC/CIM.

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.

Interaction of 22 risk SNPs with Helicobacter pylori infection and risk of gastric cardia adenocarcinoma.

Aim: To determine the prevalence of Helicobacter pylori infection and correlation between H. pylori infection and single nucleotide polymorphism (SNPs) identified in gastric cardia adenocarcinoma (GCA) patients. Methods: A case control study was performed. 22 risks of GCA-related SNPs were identified by genotyping assay and the relationship between susceptibility loci for GCA and H. pylori infection was further analyzed. Results: Helicobacter pylori infection was associated with GCA significantly (odds ratio: 1.40; 95% CI: 1.29-1.53 p<0.01). Five GCA risk SNPs had their genotypes significantly different between H. pylori positive patients and H. pylori negative patients. Conclusion: The interaction between SNPs susceptibility loci and H. pylori infection is associated with an increased risk of GCA.

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.

Overweight Patterns Between Childhood and Early Adulthood and Esophageal and Gastric Cardia Adenocarcinoma Risk.

Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are among the most rapidly increasing cancers in Western countries. Elevated BMI in adulthood is a known risk factor, but associations in early life are unclear. This study assessed weight change between childhood and early adulthood in relation to EA/GCA. Measured weights and heights during childhood (7-13 years) and early adulthood (17-26 years) were available for 64,695 young men from the Copenhagen School Health Records Register and the Danish Conscription Database. Individuals were categorized as having normal weight or overweight. Linkage with the Danish Cancer Registry identified 275 EA/GCA cases. Hazard ratios (HR) and 95% CI were estimated using Cox proportional hazards regression. The risk of EA/GCA was 2.5 times higher in men who were first classified as having overweight at age 7 (HR = 2.49; 95% CI: 1.50-4.14) compared with men who were never classified as having overweight. Men who had persistent overweight at ages 7 and 13 and in early adulthood had an EA/GCA risk that was 3.2 times higher (HR = 3.18; 95% CI: 1.57-6.44). However, there was little evidence of increased EA/GCA risk for men with overweight during childhood and subsequent remittance by early adulthood. Persistent overweight in early life is associated with increased EA/GCA risk, which declines if body weight is reduced.

Clinical implication of telomere length-related polymorphisms in gastric cardia adenocarcinoma.

e15502 Background: Aberrant telomere lengthening is a critical feature of malignant cells. Short leukocyte telomere length (LTL) confers elevated risk of gastric cardia adenocarcinoma (GCA). Multiple genome-wide association studies (GWAS) identified various single nucleotide polymorphisms (SNPs) associated with LTL in different ethnic populations. However, it remains largely unexplored how these genetic variants are involved in GCA susceptibility. Methods: We systematically screened GWAS-identified candidate SNPs and tested the impact of thirty polymorphisms in genes associated with interindividual LTL variation on GCA using two-stage case-control comparisons consisting of 1,024 GCA patients and 1,118 controls. Results: We observed that CXCR4 rs6430612, TERT rs10069690 and rs2853676 as well as VPS34 rs2162440 are significantly associated with GCA development. A 0.64-fold decreased risk of GCA is associated with the CXCR4 rs6430612 CT genotype compared with the CC genotype ( P= 0.002). On the contrary, the TERT rs10069690 TT genotype carriers had a 1.83-fold increased risk to develop GCA compared to the CC genotype carriers ( P= 5.8×10-6). We also detected a 2.17-fold increased OR for GCA that was associated with the TERT rs2853676 TT genotype ( P= 2.6×10-6). In addition, the odds of having the VPS34 rs2162440 GA genotype in GCA patients was 1.35 compared with the GG genotype ( P= 0.002). In stratified analyses, the association between TERT rs10069690 polymorphism and GCA was more pronounced in nonsmokers ( Pinteraction=9.7×10-5) and nondrinkers ( Pinteraction= 4.6×10-5). Conclusions: Our results highlight the importance of both LTL and LTL-related genetic variants to GCA predisposition.

Genetic variations associated with telomere length confer risk of gastric cardia adenocarcinoma.

Aberrant telomere lengthening is a critical feature of malignant cells. Short leukocyte telomere length (LTL) confers elevated risk of gastric cardia adenocarcinoma (GCA). Multiple genome-wide association studies (GWAS) identified various single-nucleotide polymorphisms (SNPs) associated with LTL in different ethnic populations. However, it remains largely unexplored how these genetic variants are involved in GCA susceptibility. We systematically screened GWAS-identified candidate SNPs and tested the impact of 30 polymorphisms in genes associated with interindividual LTL variation on GCA using two-stage case-control comparisons consisting of 1024 GCA patients and 1118 controls. We observed that CXCR4 rs6430612, TERT rs10069690, and rs2853676 as well as VPS34 rs2162440 are significantly associated with GCA development. A 0.64-fold decreased risk of GCA is associated with the CXCR4 rs6430612 CT genotype compared with the CC genotype (P = 0.002). On the contrary, the TERT rs10069690 TT genotype carriers had a 1.83-fold increased risk to develop GCA compared to the CC genotype carriers (P = 5.8×10-6). We also detected a 2.17-fold increased OR for GCA that was associated with the TERT rs2853676 TT genotype (P = 2.6×10-6). In addition, the odds of having the VPS34 rs2162440 GA genotype in GCA patients were 1.35 compared with the GG genotype (P = 0.002). In stratified analyses, the association between TERT rs10069690 polymorphism and GCA was more pronounced in nonsmokers (Pinteraction=9.7 × 10-5) and nondrinkers (Pinteraction=4.6 × 10-5). Our results highlight the importance of both LTL and LTL-related genetic variants to GCA predisposition.

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.

Leukocyte telomere length and risk of gastric cardia adenocarcinoma

As a chromosome stabilizer, telomeres play an essential part in maintaining the stability and integrity of human genome. Shortened telomeres have been associated with the development of cancers but it is still largely unclear whether leukocyte telomere length contributes to predisposition of gastric cardia adenocarcinoma (GCA). We conducted a case-control study consisting of 524 GCA cases and 510 controls to assess the association between telomere length in peripheral blood leukocytes and GCA risk in a Chinese Han population. The GCA patients had significantly overall shorter relative leukocyte telomere length (RTL) (median ± SD: 1.10 ± 0.54) when compared with the controls (1.24 ± 0.58). Individuals with the shortest quartile of RTL performed a doubled GCA risk (OR = 2.18; 95% CI = 1.47–3.22, P = 9.90 × 10−5) when compared with those with the highest quartile. We also found that telomere shortening and smoking have a significantly synergistic effect in intensifying risk of GCA (OR = 7.03, 95% CI = 4.55–10.86, P = 1.43 × 10−18). These findings indicate that short RTL contributes to increased susceptibility of gastric cardia adenocarcinoma and might be a promising marker to identify high-risk individuals combined with lifestyle risk factors.

Abstract 5260: Alcohol consumption and risk of gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma: A prospective analysis from the NIH-AARP Diet and Health cohort

Abstract Objective: The 2016 WCRF Continuous Update Project reported that consumption of alcoholic drinks probably causes gastric cancer, but the magnitude of the association was small, there was moderate heterogeneity among the studies included in the meta-analysis, and most studies were from Asian populations, with only 401 cases from North American studies. Therefore, we re-evaluated the association between alcohol intake and gastric cancer in a large US cohort that has accrued more than 1300 gastric cancer cases. Methods: We prospectively investigated the associations of alcohol consumption with gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA) in 490,605 members aged 50-71 years at baseline in the NIH-AARP Diet and Health Study cohort. Alcohol consumption was assessed during the baseline questionnaire in 1995/1996 and evaluated as grams of ethanol intake and as a categorical variable: never, up to or including one drink/day, one to three drinks/day, and greater than three drinks/day. We used Cox proportional hazard regression to calculate the hazard ratios and 95% confidence intervals for associations between alcohol intake and risk of gastric adenocarcinomas with adjustment for several potential confounders. Results: Through 2011, 662 incident cases of GCA and 713 of GNCA occurred in the cohort. We found no association between higher alcohol consumption and GCA or GNCA, regardless of whether analyzed as total alcoholic beverage intake or the individual beverage types of beer, wine and liquor and no evidence for a dose-response. Furthermore, we observed no association by stratum of sex, ethnic group, educational level, or smoking status. Although there were no overall associations, we found some evidence for lower risk of GNCA among people who drank up to one drink per day (HR=0.81, 95%CIs:0.67-0.97) compared to nondrinkers. Conclusion: Alcohol consumption was not associated with increased risk of gastric cardia adenocarcinoma or gastric non-cardia adenocarcinoma in this large US prospective cohort. Citation Format: ShaoMing Wang, Neal D. Freedman, Erikka Loftfield, Xing Hua, Christian C. Abnet. Alcohol consumption and risk of gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma: A prospective analysis from the NIH-AARP Diet and Health cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5260.

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.

Tree nut, peanut, and peanut butter consumption and the risk of gastric and esophageal cancer subtypes: the Netherlands Cohort Study

BackgroundNut consumption has been associated with reduced cancer-related mortality. However, it is unclear whether nut consumption also reduces the risk of esophageal and gastric cancer subtypes. We prospectively investigated the relationship of tree nut, peanut, and peanut butter intake with risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA) in the Netherlands Cohort Study.MethodsIn 1986, 120,852 males and females, aged 55–69 years, completed a baseline questionnaire on diet and cancer risk factors. After 20.3 years of follow-up, 133 ESCC, 200 EAC, 191 GCA, and 586 GNCA cases, and 3,720 subcohort members were available for multivariable Cox regression analyses, using a case–cohort approach.ResultsIncreased total nut consumption was significantly associated with a decreased risk of ESCC and GNCA [HRs (95% CIs) for 10 + g/day vs. nonconsumers = 0.54 (0.30–0.96) and 0.73 (0.55–0.97), respectively], but not with EAC and GCA risk. Similar trends were observed for tree nut and peanut intake, which were mostly nonsignificant. For peanut butter intake, no significant associations were found. When excluding the first four years of follow-up to reduce the possible influence of reversed causation, the relation between nut consumption and ESCC risk attenuated, but remained inverse.ConclusionsOur findings suggest that increased tree nut and peanut consumption is inversely associated with GNCA risk and possibly with ESCC risk, but not with the risk of the other esophageal and gastric cancer subtypes.

Nut and peanut butter consumption and the risk of esophageal and gastric cancer subtypes

Background: Nut consumption has been associated with decreased risk of colorectal, endometrial, lung, and pancreatic cancers. Polyphenols, fiber, vitamins, and minerals in nuts may confer this observed protective effect. To our knowledge, no prospective study has evaluated the effect of nut consumption on esophageal and gastric cancers.Objective: The objective was to evaluate the associations between nut and peanut butter consumption and the risk of esophageal and gastric cancers and their different subtypes.Design: In this study we used data from the NIH-AARP Diet and Health Study, which enrolled 566,407 persons who were 50-71 y old at baseline (1995-1996). The median follow-up time was 15.5 y. Intakes of nuts and peanut butter were assessed through the use of a validated food-frequency questionnaire. We used Cox proportional hazard models to estimate HRs and 95% CIs for esophageal and gastric cancers and their subtypes.Results: We identified 966 incident cases of esophageal adenocarcinomas, 323 cases of esophageal squamous cell carcinoma, 698 cases of gastric cardia adenocarcinoma, and 732 cases of gastric noncardia adenocarcinoma. Compared with those who did not consume nuts or peanut butter [lowest category of consumption (C0)], participants in the highest category of nut consumption (C3) had a lower risk of developing gastric noncardia adenocarcinoma [C3 compared with C0, HR: 0.73 (95% CI: 0.57, 0.94)]. This inverse association was also seen for peanut butter consumption [C3 compared with C0, HR: 0.75 (95% CI: 0.60, 0.94)]. We observed no significant associations between the highest and lowest intakes of nuts or peanut butter and the risk of gastric cardia adenocarcinoma, esophageal adenocarcinoma, or esophageal squamous cell carcinoma.Conclusions: Among older American adults, both nut and peanut butter consumption were inversely associated with the risk of gastric noncardia adenocarcinoma. This trial was registered at clinicaltrials.gov as NCT00340015.

Body weight trajectories and risk of oesophageal and gastric cardia adenocarcinomas: a pooled analysis of NIH-AARP and PLCO Studies

Background:Elevated body mass index (BMI, kg m−2) has been consistently associated with oesophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) incidence. However, effects of adiposity over the life course in relation to EA/GCA have not been thoroughly explored.Methods:We pooled two prospective cohort studies: NIH-AARP Diet and Health Study and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, with data on 409 796 individuals (633 EA, 415 GCA). At baseline, participants reported their height and weight at ages 20 and 50 years, and current. Body mass index trajectories were determined using latent class analysis. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression.Results:Compared with individuals with a BMI<25 kg m−2 at all time points, exceeding a BMI of 25 kg m−2 at age 20 was associated with increased risks of EA (HR=1.76, 95% CI: 1.35–2.29) and GCA (HR=1.62, 95% CI: 1.16–2.25). Similarly, a BMI trajectory of overweight (⩾25–<30 kg m−2) at age 20 progressing to obesity (⩾30 kg m−2) by age 50 was associated with increased risks of EA (HR=2.90, 95% CI: 1.67–5.04) and GCA (HR=4.07, 95% CI: 2.32–7.15), compared with individuals with a normal weight (⩾18.5–<25 kg m−2) trajectory. Weight gain of ⩾20 kg between age 20 and baseline was also associated with a two times increased risk of EA (HR=1.97, 95% CI: 1.43–2.73) and more modestly with GCA (HR=1.40, 95% CI: 0.96–2.05).Conclusions:Being overweight in early adulthood and weight gain later in life were each associated with increased risks of EA and GCA. This underscores the potential of weight control programs for reducing EA and GCA risk.

Association of genotypes of rs671 withinALDH2 with risk for gastric cardia adenocarcinoma in the Chinese Han population in high- and low-incidence areas.

Objective: This study aimed to determine if gastric cardia adenocarcinoma (GCA) risk was associated with the lys (A or *2) allele at the rs671 (glu504lys) polymorphism within the aldehyde dehydrogenase 2 (ALDH2) gene in a Chinese Han population. We also aimed to investigateALDH2 genotypic distributions between subjects from high- and low-incidence areas for both GCA and esophageal squamous cell carcinoma (ESCC). Methods: We designed a case-control study including 2,686 patients with GCA and 3,675 control subjects from high- and low-incidence areas for both GCA and ESCC in China. TaqMan allele discrimination assay was used to genotype the rs671 polymorphism.χ2 test and binary logistic regression analysis were used to estimate the odds ratios for the development of GCA, and multivariate ordinal logistic regression was used to analyzeALDH2 genotypic distributions among different groups. Results: Compared withALDH2*1/*1 homozygotes,ALDH2*1/*2 andALDH2*2/*2 carriers did not increase the risk for GCA in the Chinese Han population (P>0.05). Interestingly, the ratio of homozygous or heterozygousALDH2 *2 carriers in high-incidence areas for both GCA and ESCC was lower than that in low-incidence areas (P<0.001). Conclusions: Genotypes of rs671 atALDH2 may not increase GCA susceptibility in Chinese Han populations. In addition, theALDH2 genotypic distribution differs between Chinese Han populations from high- and low-incidence areas for both GCA and ESCC. Our findings may shed light on the possible genetic mechanism for the dramatic geographic differences of GCA occurrence in China.

Prospective study of serum B vitamins levels and oesophageal and gastric cancers in China.

B vitamins play an essential role in DNA synthesis and methylation, and may protect against oesophageal and gastric cancers. In this case-cohort study, subjects were enrolled from the General Population Nutrition Intervention Trial in Linxian, China. Subjects included 498 oesophageal squamous cell carcinomas (OSCCs), 255 gastric cardia adenocarcinomas (GCAs), and an age- and sex-matched sub-cohort of 947 individuals. Baseline serum riboflavin, pyridoxal phosphate (PLP), folate, vitamin B12, and flavin mononucleotide (FMN) were measured for all subjects. We estimated the associations with Cox proportional hazard models, with adjustment for potential confounders. Compared to those in the lowest quartile of serum riboflavin, those in the highest had a 44% lower risk of OSCC (HR: 0.56, 95% CI: 0.41 to 0.75). Serum vitamin B12 as a continuous variable was observed to be significantly inversely associated with OSCC (HR: 0.95, 95% CI: 0.89 to 1.01, P for score test = 0.041). Higher serum FMN levels were significantly associated with increased risk of OSCC (HR: 1.08, 95% CI: 1.01 to 1.16) and GCA (HR: 1.09, 95% CI: 1.00 to 1.20). Our study prompted that B vitamins have the potential role as chemopreventive agents for upper gastrointestinal cancers.