Gastric Noncardia Research Articles

Body mass index and esophageal and gastric cancer: A pooled analysis of 10 population-based cohort studies in Japan.

The effect of body mass index (BMI) on esophageal and gastric carcinogenesis might be heterogeneous, depending on subtype or subsite. However, findings from prospective evaluations of BMI associated with these cancers among Asian populations have been inconsistent and limited, especially for esophageal adenocarcinoma and gastric cardia cancer. We performed a pooled analysis of 10 population-based cohort studies to examine this association in 394,247 Japanese individuals. We used Cox proportional hazards regression to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs), then pooled these estimates to calculate summary HRs with a random effects model. During 5,750,107 person-years of follow-up, 1569 esophageal cancer (1038 squamous cell carcinoma and 86 adenocarcinoma) and 11,095 gastric (728 cardia and 5620 noncardia) cancer incident cases were identified. An inverse association was observed between BMI and esophageal squamous cell carcinoma (HR per 5-kg/m2 increase 0.57, 95% CI 0.50-0.65), whereas a positive association was seen in gastric cardia cancer (HR 1.15, 95% CI 1.00-1.32). A nonsignificant and significant positive association for overweight or obese (BMI ≥25 kg/m2 ) relative to BMI <25 kg/m2 was observed with esophageal adenocarcinoma (HR 1.32, 95% CI 0.80-2.17) and gastric cardia cancer (HR 1.24, 95% CI 1.05-1.46), respectively. No clear association with BMI was found for gastric noncardia cancer. This prospective study-the largest in an Asian country-provides a comprehensive quantitative estimate of the association of BMI with upper gastrointestinal cancer and confirms the subtype- or subsite-specific carcinogenic impact of BMI in a Japanese population.

Incidence of gastrointestinal malignancies increases in persons received eradication therapy for Helicobacter pylori: A cohort study.

Long-term Helicobacter pylori infection increases the risk of gastric malignancies. Since the symptoms for H. pylori gastritis, as well as for several malignancies, may be nonexisting or highly unspecific, even H. pylori-positive subjects with underlying malignancies may receive eradication therapy. The aim was to assess the incidence of gastrointestinal and various other malignancies in individuals after eradication therapy for H. pylori infection. A cohort of 217,554 subjects (120,344 women and 97,210 men), who had purchased specific combinations of drugs for H. pylori eradication therapy in 1994-2004, was identified by the Finnish National Prescription Registry and followed for cancer incidence until the end of 2008 (1.89 million person-years at risk). A total of 22,398 malignancies were identified in the cohort. In both genders, for the first 6 months after drug prescription, the standardized incidence ratios (SIRs) were between 5 and 32 for gastric, colorectal, and pancreatic cancers, and 2 and 3 for several other malignancies. Although later on the SIRs of most malignancies fell rapidly, those of gastric noncardia and lung cancers remained elevated up to 5 years of follow-up. The only SIRs below unity were seen in men for gastric cancers (cardia 0.61, 95% CI: 0.37-0.95; intestinal noncardia 0.74, 95% CI: 0.56-0.97) during the post-therapy period covering years 5-15. Incidence levels significantly above the population rates were detected for many malignancies. Although eradication of H. pylori may have a long-lasting protective effect against gastric cancer, H. pylori therapy may postpone the detection of malignancies possibly underlying unspecific gastrointestinal symptoms. Therefore, it should be emphasized that the diagnostic work-up for malignancies should not be stopped in case of detection and treatment of H. pylori infection.

Combined risk factors and risk of upper gastrointestinal cancer mortality in the Linxian general population.

We aimed to explore the association of combined risk factors with risk of death from upper gastrointestinal (UGI) cancer, including esophageal squamous cell carcinoma (ESCC), gastric cardia carcinoma (GCC) and gastric noncardia carcinoma (GNCC) in the Linxian Nutrition Intervention Trial (NIT) cohort. The NIT cohort included 29 584 healthy adults. A combined risk score (CRS) was calculated using a point system method based on 10 risk factors collected at baseline, including gender, smoking, alcohol drinking, body mass index, family history of UGI cancer, drinking tap water, tooth loss and consumption of fresh fruit, eggs and meat. Possible score ranged from 0 to 31, and higher score indicated as poorer health status. Subjects were divided into three groups by the CRS (<12 points, 12 to 20 points and >20 points). The group of CRS <12 points was considered as the reference. During the 30-year follow-up, we identified 4553 UGI cancer deaths. Compared to subjects with a CRS <12 points, the adjusted HRs for CRS of 12 to 20 points and >20 points were 1.69 (95% CI: 1.56-1.83) and 3.06 (95% CI: 2.82-3.33) for UGI cancer mortality, respectively (Ptrend < .001). Comparable associations were also observed for ESCC, GCC and GNCC mortality. Results remained similar across different age groups (Pinteraction > .05). All HRs observed in the second half follow-up period were stronger than that observed in the first half follow-up period. Our study indicated that higher CRS was associated with increased risk of UGI cancer mortality. Appropriate measures should be taken to reduce unhealthy lifestyles.

Global and national trends in the age-specific sex ratio of esophageal cancer and gastric cancer by subtype.

A male predominance was observed in esophageal and gastric cancers, though present limited data has revealed variations by age. We aim to investigate the global age‐specific sex differences in esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). Data on esophageal and gastric cancers incidence by diagnosis year, sex, histology, subsite and age group were extracted from 171 registries in 54 countries included in the last two volumes (X and XI, 2003‐2012) of Cancer Incidence in Five Continents, which contributing to over 80% of the global burdens of these cancers. Age‐standardized incidence rates (ASIRs) and male‐to‐female ASIRs ratios were estimated for esophageal and gastric cancers, by histological subtype and subsite, globally and by country. We consistently observed a male predominance in esophageal and gastric cancers across the world from 2003 to 2012, with male‐to‐female ASIRs ratios of 6.7:1 for EAC, 3.3:1 for ESCC, 4.0:1 for GCC and 2.1:1 for GNCC. The sex differences were consistent across time periods but varied significantly by age across the life span. Across the four cancer types, the male‐to‐female incidence rate ratios increased from young ages, approaching a peak at ages 60‐64, but sharply declined thereafter. Similar “low‐high‐low” trends of age‐specific sex ratio were observed in other digestive cancers including liver, pancreas, colon and rectum with peak ages ranging from 50 to 65. Age‐dependent risk factors warrant further investigation to aid our understanding of the underlying etiologies of esophageal and gastric cancers by histological subtype and subsite.

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.

Abstract 787: Estimating the influence of sex on cancer risk: An analysis in a large US prospective cohort study

Abstract Historically in the United States, cancer incidence has been significantly higher in men than women. This disparity is often attributed to gender-related behavioral risk factors, such as smoking and drinking. The degree to which differences in age-adjusted cancer rates are due to sex (e.g., chromosomes, hormones) is unknown. We estimated the effect of sex on cancer risk by comparing cancer incidence at 21 shared sites between men and women while adjusting for known gender-related risk factors. We analyzed data from 122,826 women and 171,274 men enrolled in the NIH AARP Diet and Health Study (1995-2011), contributing 3.5 million person-years of follow-up. Cox proportional hazards models were used to estimate male-to-female (M:F) adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for each of the cancers, controlling for relevant baseline cancer-specific demographic (age, race, marital status, education), lifestyle (self-reported health status, family history of cancer, diet, body mass index, physical activity), and behavioral factors (tobacco, alcohol use). We used the Peters-Belson method to partition the observed differences between the sexes in cancer incidence into the proportion of the difference explained by the modifiable environmental and behavioral exposures (explained disparity) and the remaining proportion that cannot be explained by these exposures (unexplained disparity). After adjustment for cancer-specific risk factors, risks remained significantly higher in men for nearly all sites. The highest M:F aHR was for esophageal adenocarcinoma (aHR: 10.59, 95% CI: 7.19, 15.61) followed by gastric cardia (aHR: 4.55, 95% CI: 3.28, 6.31) and larynx (aHR: 3.73, 95% CI: 2.84, 4.89) cancers. In contrast, men had a lower adjusted incidence of thyroid (aHR: 0.57, 95% CI: 0.48, 0.68) and gallbladder (aHR: 0.55, 95% CI: 0.37, 0.82) cancers compared with women. Using the Peters-Belson method we found that, if men had the same exposure distribution as the women (under a counterfactual), the male predominance would remain for 12 cancers (bladder, skin, lung, colon, kidney, rectum, esophageal adenocarcinoma, larynx, gastric cardia, esophageal squamous cell carcinoma, pancreas, and oropharynx). For 4 cancers (liver, gastric non-cardia, oral cavity, and anus), if men had the exposure distribution of women, they would have experienced a higher cancer incidence than what was observed. This elevated risk in men compared with women, after adjustment for risk factors, indicates potential innate sex differences across nearly all shared cancer sites. Funding: Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics Citation Format: Sarah S. Jackson, Morgan A. Marks, Hormuzd Katki, Barry I. Graubard, Michael D. Cook, Anil Chaturvedi. Estimating the influence of sex on cancer risk: An analysis in a large US prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 787.

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.

A long-term follow-up analysis of associations between tooth loss and multiple cancers in the Linxian General Population cohort

Poor oral health, indicated by tooth loss and periodontal disease, may be an important risk factor for various cancers. Prior studies have found inconsistent associations between tooth loss and several cancer types. Here, we examined the relationship between tooth loss and incident cases of multiple cancers in the Linxian General Population Nutrition Intervention Trial cohort. In this large prospective cohort of over 29,000 participants, there were 3101, 1701, 626, 327, 348, and 179 incident esophageal, gastric cardia, gastric noncardia, liver, lung, and colorectal cancer cases, respectively, over 30 years of follow-up. Adjusted Cox proportional hazards regression models with time-varying covariates were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between tooth loss and cancer outcomes during three time intervals: ≤ 5 years (early), > 5 and ≤ 10 years (mid), > 10 years (late). Tooth loss was assessed as quartiles of the number of lost teeth in excess of the loess-smoothed, age-specific median number of teeth lost. For esophageal cancer, the increase in risk associated with the highest quartile of tooth loss was 25% (95% CI: 1.02, 1.52) in the mid time interval, but the association weakened thereafter. For gastric cardia cancer, the increase in risk associated with the highest quartile of tooth loss was 1.34 in both the early (95% CI: 1.06, 1.71) and mid time intervals (95% CI: 1.02, 1.76), with no significant associations in the late interval. Gastric noncardia cancer was only associated with the second quartile of tooth loss in the late time interval (HR = 1.54; 95% CI: 1.16, 2.04). All associations between tooth loss and liver, lung, and colorectal cancers were null. Tooth loss was associated with risk of esophageal and gastric cancers in this updated analysis from the cohort.

Oral leukoplakia and the long-term risk of upper gastrointestinal cancer deaths in the Linxian dysplasia population.

BackgroundTo investigate oral leukoplakia (OL) and risk of upper gastrointestinal (UGI) cancer deaths in the Linxian Dysplasia Nutrition Intervention Trial (NIT) cohort.MethodsA total of 3318 subjects with esophageal squamous dysplasia enrolled on 1 May 1985, and were followed up until 30 September 2015. Participants with OL at baseline were treated as an exposed group, while the remainder was selected as a control group. All subjects were followed monthly and reviewed quarterly by the Linxian Cancer Registry. Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs).ResultsDuring the 30‐year follow‐up, a total of 902 UGI cancer deaths occurred, including 541 esophageal squamous cell carcinoma (ESCC) related, 284 gastric cardia carcinoma (GCC) related, and 77 gastric noncardia carcinoma (GNCC) related deaths. Relative to subjects without OL, the long‐term risk of ESCC mortality in participants with OL increased by 26.1% (HR = 1.26, 95% CI: 1.05–1.52). In the subgroup analyses, adverse effects of OL on ESCC mortality were observed especially in younger subjects (HR = 1.48, 95% CI: 1.11–1.97), females (HR = 1.44, 95% CI: 1.11–1.89), non‐smokers (HR = 1.44, 95% CI: 1.15–1.81), nondrinkers (HR = 1.28, 95% CI: 1.04–1.57), and individuals with a family history of cancer (HR = 1.37, 95% CI: 1.05–1.79). No associations were observed between OL and risk of GCC and GNCC mortality.ConclusionsOL may increase the long‐term risk of ESCC mortality, especially in younger subjects, females, nondrinkers, non‐smokers, and subjects with a family cancer history. Future studies are needed to explore the potentially etiological mechanism.

Abstract D105: Differences in receipt of surgery contribute to survival disparities in esophageal and gastric cancers

Abstract Introduction: Mortality disparities for gastrointestinal cancers are well described. Differences in rates of surgery across race and ethnicity may contribute to this phenomenon. In order to evaluate this, we assessed the extent to which the mortality disparity among racial/ethnic groups for gastrointestinal cancers are due to differences in operative rates. Methods: Data for patients with stage I-III esophageal and gastric cancer diagnoses between 2004-2015 were obtained from National Cancer Database. Cancers were categorized in 3 groups: mid-esophageal (ME) cancers, distal third of esophagus and cardia gastric cancers (DEC), and non-cardia gastric (NCG) cancers. Variables included demographics, receipt of surgery, tumor stage and characteristics, and hospital factors. The racial disparity in survival was measured as the hazard ratio (HR) for Black, Latinx, and Asian/Pacific Islander patients compared to White patients. A mediation analysis was performed to quantify the contribution of variables to the observed disparity between minority and White patients. The magnitude of the contributions was estimated using two methods: the change in HR with (1) the addition of each variable of interest to a model only adjusted by age and year, and (2) the removal of each variable from a multivariate model that included all variables. Factors associated with undergoing surgery were also examined using a logistic regression model. Results: A total of 124,862 patients were included (20,852 with ME, 74,427 with DEC, and 29,583 with NCG). Black patients were more likely to be from lower-income and urban areas and had lower operative rates in all cancers. The observed HRs for Black patients compared to White patients were 1.42 (95% CI 1.36-1.49) for ME, 1.36 (1.31-1.43) for DEC and 1.01 (0.97-1.05 – no observed disparity) for NCG tumors, adjusting for age and year of diagnosis. Only Black race/ethnicity was associated with a mortality disadvantage compared to White patients. Without adjustment for any additional variables, receipt of surgery accounted for more than half of the observed survival disparity for tumors of the esophagus and cardia (ΔHRs for ME: 0.27, DECS: 0.25 and NCG: 0.07). After adjustment for tumor, patient and hospital factors, receipt of surgery remained the single strongest contributor to the Black/White disparity in survival for all cancers (ΔHRs for ME: 0.070, DEC: 0.091 and NCG: 0.07). On logistic regression, Black patients were less likely to have received surgery after adjusting for other variables compared to White patients (ME aOR: 0.41 (0.37-0.46), DECS aOR: 0.42 (0.39-0.46), and NCG aOR: 0.79 (0.73-0.86)). Conclusions: Observed survival disparities in upper GI cancers may be due to fewer surgeries being performed for Black patients. Addressing differences in receipt of surgery for stage I through III esophageal and proximal stomach cancer has potential to mitigate cancer mortality disparities. Citation Format: John Bliton, Peter Muscarella, Michael Parides, Katia Papalezova, John McAuliffe, Haejin In. Differences in receipt of surgery contribute to survival disparities in esophageal and gastric cancers [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 D105.

Five Serum Trace Elements Associated with Risk of Cardia and Noncardia Gastric Cancer in a Matched Case-Control Study.

BackgroundSerum trace elements have for some time been suggested to influence the development of gastric cancer, but evidence is still lacking.MethodsAll newly diagnosed patients with gastric cancer were compared with healthy controls 1:1 matched by sex, age (±3 years), and place of residence during 2013–2015. The serum concentration of all trace elements was analyzed using inductively coupled plasma mass spectrometry. Heliobacter pylori infections in cases were diagnosed using the rapid urease test, while in controls were detected using the colloidal gold method.ResultsA total of 122 cases of gastric cardia cancer (GCC) and 177 gastric noncardia cancer (NCGC), and 299 matched healthy controls were included. Positive associations were found between serum copper and copper/zinc ratio and risk of overall gastric cancer (OR4th vs 1st quartile: 2.42, 95% CI: 1.10–5.32 for copper; OR4th vs 1st quartile: 11.7, 95% CI: 3.83–35.6 for copper/zinc ratio), and for both GCC and NCGC subtypes. Serum selenium was inversely associated with the risk of NCGC (OR4th vs 1st quartile: 0.18, 95% CI: 0.07–0.51), while molybdenum seems to reduce the risk of GCC (OR4th vs 1st quartile: 0.12, 95% CI: 0.03–0.47). Strong inverse associations were also detected between serum calcium and risk of all groups of gastric cancer (all p for trend<0.05).ConclusionThe current study indicated statistically significant positive associations between serum copper, copper/zinc ratio, and gastric cancer, as well as inverse associations among selenium, molybdenum, and calcium. The results shall be carefully interpreted before further in vivo animal studies show definitive evidence.

Fresh fruit consumption may decrease the long-term risk of esophageal cancer mortality: A 30-year follow-up study in the Linxian Dysplasia Nutrition Intervention trial (NIT).

BackgroundThe objective of this study was to explore the association between fresh fruit consumption and long‐term risk of upper gastrointestinal cancer (UGI) in the Linxian Dysplasia Nutrition Intervention Trial (NIT) cohort.MethodsA cohort of 3318 subjects with esophageal squamous dysplasia participated in the Linxian Dysplasia NIT in May 1985 and were followed up until 30 September 2015. Demographic characteristics, lifestyle, and history of diseases were collected at the baseline. The primary endpoint was death from esophageal squamous cell carcinoma (ESCC), gastric cardia carcinoma (GCC), and gastric noncardia carcinoma (GNCC). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard model.ResultsIn the 30‐year follow‐up, a total of 541 ESCC, 284 GCC, and 77 GNCC deaths occurred. Relative to those who never or rarely consumed fresh fruit, the risk of ESCC mortality in participants who consumed fresh fruit more than 12 times/year were significantly decreased by 37.3% (HR = 0.63, 95% CI: 0.49–0.81). In the subgroup analyses, significantly protective effects on ESCC mortality were observed especially in females (HR = 0.59, 95% CI: 0.40–0.89), non‐smokers (HR = 0.67, 95% CI: 0.48–0.94), and nondrinkers (HR = 0.69, 95% CI: 0.51–0.93).ConclusionsConsuming fresh fruit more than 12 times/year may reduce the long‐term risk of ESCC mortality in this dysplasia population, particularly in females, non‐smokers, and nondrinkers. Future studies are needed to confirm these findings.

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.

Prognostic effect of different etiologies in patients with gastric cardia cancer.

There are still many controversies about the characteristics and prognosis of gastric cardia cancer. We aimed to evaluate the clinical characteristics and outcome between cardia and noncardia cancer. Also, we evaluated the clinical outcome according to etiologic factors.We performed a retrospective cohort study of 92 patients with gastric cardia cancer from January 2003 to December 2013. The patients with noncardia cancer were selected as age- and sex-matched control.The frequencies of gastroesophageal reflux disease (GERD) and negative Helicobacter pylori infection without atrophy were significantly higher in gastric cardia cancers, but there was no difference in the frequency of obesity. The frequency of early gastric cancers was 40.0%, which was significantly lower than that of noncardia cancer. The rate of recurrence, disease-free survival, and overall survival duration were significantly lower in gastric cardia cancers (P < .01), even though there was no significant difference in the rate of curative resection (R0). In terms of the etiologic factors, there were no differences of disease prognosis, regardless of the presence of GERD, obesity, and H pylori infection with associated gastritis.Gastric cardia cancer showed distinct clinical characteristics and a negative prognostic impact compared with gastric noncardia cancer.

SEPATH: benchmarking the search for pathogens in human tissue whole genome sequence data leads to template pipelines

BackgroundHuman tissue is increasingly being whole genome sequenced as we transition into an era of genomic medicine. With this arises the potential to detect sequences originating from microorganisms, including pathogens amid the plethora of human sequencing reads. In cancer research, the tumorigenic ability of pathogens is being recognized, for example, Helicobacter pylori and human papillomavirus in the cases of gastric non-cardia and cervical carcinomas, respectively. As of yet, no benchmark has been carried out on the performance of computational approaches for bacterial and viral detection within host-dominated sequence data.ResultsWe present the results of benchmarking over 70 distinct combinations of tools and parameters on 100 simulated cancer datasets spiked with realistic proportions of bacteria. mOTUs2 and Kraken are the highest performing individual tools achieving median genus-level F1 scores of 0.90 and 0.91, respectively. mOTUs2 demonstrates a high performance in estimating bacterial proportions. Employing Kraken on unassembled sequencing reads produces a good but variable performance depending on post-classification filtering parameters. These approaches are investigated on a selection of cervical and gastric cancer whole genome sequences where Alphapapillomavirus and Helicobacter are detected in addition to a variety of other interesting genera.ConclusionsWe provide the top-performing pipelines from this benchmark in a unifying tool called SEPATH, which is amenable to high throughput sequencing studies across a range of high-performance computing clusters. SEPATH provides a benchmarked and convenient approach to detect pathogens in tissue sequence data helping to determine the relationship between metagenomics and disease.

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.

Risk and Predictors of Esophageal and Stomach Cancers in HIV-Infected Veterans: A Matched Cohort Study.

To evaluate the risks of esophageal and stomach carcinomas in people living with HIV (PLWH) compared with the general population and risk factors for these cancers in PLWH. Retrospective cohort study in the Veterans Health Administration. We compared incidence rates for esophageal and stomach cancers in 44,075 HIV-infected male veterans with those in a matched HIV-uninfected cohort (N = 157,705; 4:1 matched on age and HIV-index date). We used Cox regression models to estimate Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with HIV infection and for cancer risk factors in PLWH. In unadjusted models, HIV infection was associated with increased risks of esophageal squamous cell carcinoma (ESCC; HR, 2.21; 95% CI: 1.47 to 3.13) and gastric cardia cancer (HR, 1.69; 95% CI: 1.00 to 2.85) but associated with lower risk of esophageal adenocarcinoma (EAC; HR, 0.48; 95% CI: 0.31 to 0.74). After adjusting for age, race/ethnicity, smoking and alcohol use, HIV infection remained statistically significantly associated with elevated risk for ESCC [adjusted hazard ratio (aHR), 1.58; 95% CI: 1.02 to 2.47], especially among HIV-infected patients with CD4 count ≤200 (aHR, 2.20; 95% CI: 1.35 to 3.60). HIV infection was not associated with risks of EAC (aHR, 0.82; 95% CI: 0.53 to 1.26), gastric cardia (aHR, 0.80; 95% CI: 0.33 to 1.94), or noncardia (aHR, 1.06; 95% CI: 0.61 to 1.84) cancers. Risk factors for these cancers in HIV-infected patients were otherwise similar to those in general population (eg, Helicobacter pylori for gastric noncardia cancer). HIV-infected individuals with low CD4 count are at highest risk for ESCC, but HIV infection was not independently associated with EAC or gastric cancer after adjusting for confounders.

Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow‐up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist‐to‐hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.