Non-cardia Cancer 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.

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.

Trends in age-standardised net survival of stomach cancer by subsite and stage: A population-based study in Osaka, Japan, 2001-2014

IntroductionThe burden of stomach cancer remains high, particularly among Asian countries. Although Japan is known to achieve high survival from stomach cancer, little is known regarding the survival trends for recent years and survival by subsite and stage. We report age-standardised 1-, 3-, 5- and 10-year net survival for patients diagnosed with stomach cancer in Osaka, Japan. MethodsWe analysed patients diagnosed with primary stomach cancer and registered in the population-based cancer registry in Osaka Prefecture between 2001 and 2014. We used the non-parametric Pohar Perme method to derive net survival for each year. Both cohort and period approaches were used. Age was standardised using weights of the external population of the International Cancer Survival Standard. Multiple imputation was applied to handle missing information on subsite and stage before estimating age-standardised net survival by subsite (cardia and non-cardia) and stage (localised, regional and distant metastasis). We then examined general trends in the cohort-based survival estimates, as well as by subsite and stage, using linear regression. ResultsA total of 97,276 patients were included in the analysis. Age-standardised net survival improved steadily (mean annual absolute change ≥1.2%). Net survival for both subsites improved, but cardia cancer showed 7–23% lower survival than non-cardia cancer throughout the study period. Five-year net survival remained high (≥80%) in the localised stage from the beginning of this study. Net survival increased steeply (≥1.4% per year) in the regional stage. Although 1-year net survival increased by 14% in the distant stage, 5-year and 10-year net survival remained below 10%. ConclusionAge-standardised net survival for stomach cancer in Japan improved during the study period owing to an increase in the number of patients with localised stage at diagnosis and improved treatment. Monitoring both short- and long-term survival should be continued as management of stomach cancer progresses.

Diet and Risk of Gastric Cancer: An Umbrella Review.

Several dietary exposures have been associated with gastric cancer (GC), but the associations are often heterogenous and may be afflicted by inherent biases. In the context of an Umbrella Review (UR), we provide an overview and a critical evaluation of the strength and quality, and evidence classification of the associations of diet-related exposures in relation to the risk of GC. We searched PubMed and Scopus for eligible meta-analyses of observational studies published in English from inception to 12 December 2021, and for any identified association, we applied robust epidemiological validity evaluation criteria and individual study quality assessment using AMSTAR. We screened 3846 titles/abstracts and assessed 501 full articles for eligibility, of which 49 were included in the analysis, investigating 147 unique exposures in relation to GC, cardia (GCC) or non-cardia (GNCC) cancer. Supported by suggestive evidence, positive associations were found comparing the highest vs. lowest categories for: heavy (>42 g/day) alcohol consumption (Relative Risk (RR) = 1.42, 95% Confidence Interval (CI): 1.20–1.67), salted fish consumption (RR = 1.56, 95% CI:1.30–1.87) and waist circumference (RR = 1.48, 95% CI:1.24–1.78) and an inverse association for the healthy lifestyle index (RR = 0.60, 95% CI:0.48–0.74) in relation to GC. Additionally, a positive association was found comparing obese individuals (Body Mass Index (BMI) ≥ 30) to normal-weight individuals (BMI: 18.5–25) (RR = 1.82, 95% CI:1.32–2.49) in relation to GCC. Most of the meta-analyses were of medium-to-high quality (median items: 7.0, interquartile range: 6–9). Maintaining a normal body weight and adopting healthy dietary choices, in particular, limiting the consumption of salt-preserved foods and alcohol, can reduce the risk of gastric cancer.

Viral Pathogens in Oesophageal and Gastric Cancer.

Tumour virology was born with the discovery by Peyton Rous in 1911 of a filterable agent in chicken cellular extracts that caused neoplasia in healthy chickens. Universally, 20% of all human cancers have a viral aetiology. Viruses are involved at various stages of the carcinogenesis pathway, depending on the viral pathogen, and likely require co-factors. Multiple risk factors have been associated with oesophageal and gastric malignancy, including carcinogenic pathogens. These viruses and bacteria include human papillomavirus (HPV) [oesophageal cancer], Epstein–Barr virus (EBV) [proximal stomach cancer], and Helicobacter pylori (HP) [non-cardia stomach cancer]. Viruses such as EBV have been firmly established as causal for up to 10% of gastric cancers. HPV is associated with 13 to 35% of oesophageal adenocarcinoma but its role is unclear in oesophageal squamous cell carcinomas. The causal relationship between hepatitis B (HBV), cytomegalovirus (CMV), HPV, and John Cunningham (JCV) and gastric neoplasia remains indeterminate and warrants further study. The expression of viral antigens by human tumours offers preventive and therapeutic potential (including vaccination) and has already been harnessed with vaccines for HPV and HBV. Future goals include viral protein-based immunotherapy and monoclonal antibodies for the treatment of some of the subset of EBV and HPV-induced gastro-esophageal cancers.

Changing trends in gastric cancer incidence and mortality: the role of upper endoscopy in low-risk countries.

Gastric cancer, which is diagnosed in approximately one million new patients annually, is a significant contributor to global cancer burden and cancer-related mortality [1]. East Asia, eastern Europe, and Latin America have the highest incidences, while North America and most of western Europe have relatively low incidences [2]. This geographical variation is thought to be associated with several different predisposing and etiologic factors among the countries, such as tumor biology, Helicobacter pylori (H. pylori) infection rate, cigarette smoking, and a high sodium diet with salt-preserved foods. Global age-standardized gastric cancer incidence has steadily declined over the past century, particularly in high-risk countries such as Korea and Japan. This trend has been linked to a decline in noncardia cancer because of the eradication of H. pylori [2]. Contrarily, in countries with low gastric cancer incidence, such as those in western Europe and the USA, the decline in gastric cancer has reduced, especially in the middle-aged population [1] [2]. This phenomenon may also be related to changes in H. pylori infection patterns or the increased proportion of cardia cancer related to epidemic obesity and gastroesophageal reflux disease [1]. As with incidence, global gastric cancer mortality has also decreased [2]. Improvements in surgical techniques and the development of chemotherapy regimens have led to better survival outcomes. Above all, early detection of cancer is a crucial factor contributing to the decline in mortality.

Metabolic Syndrome and Risk of Gastrointestinal Cancers: An Investigation Using Large-scale Molecular Data

Background & AimsGastrointestinal cancer risk is influenced by the presence of metabolic syndrome (MetS). However, previous epidemiologic studies lacked full serological biomarker data for the classification of MetS, and the interaction of MetS with germline cancer risk variants is unknown.MethodsWe investigated the associations between MetS and gastrointestinal cancer risk (overall, colorectal, pancreatic, esophageal adenocarcinoma, esophageal squamous cell carcinoma, stomach cardia, stomach non-cardia, hepatocellular carcinoma, and intrahepatic bile duct cancer) in 366,016 United Kingdom Biobank participants with comprehensive serum biomarker and genotype data. MetS status was determined by 3 different definitions at baseline, and, in 15,152 participants, at a repeat assessment after a median of 4.3 years of follow-up. Multivariable hazard ratios and 95% confidence intervals for cancer outcomes were estimated using Cox proportional hazards models. Analyses stratified by polygenic risk score were conducted for colorectal and pancreatic cancers.ResultsDuring a median follow-up of 7.1 years, 4238 incident cases of a gastrointestinal cancer occurred. MetS at baseline was associated with higher risk of overall gastrointestinal cancer by any definition (hazard ratio, 1.21; 95% confidence interval, 1.13–1.29, harmonized definition). MetS was associated with increased risks of colorectal cancer, colon cancer, rectal cancer, hepatocellular carcinoma, pancreatic cancer in women, and esophageal adenocarcinoma in men. Associations for colorectal cancer and pancreatic cancer did not differ by polygenic risk score strata (P-heterogeneity 0.70 and 0.69, respectively), and 80% of participants with MetS at baseline retained this status at the repeat assessment.ConclusionsThese findings underscore the importance of maintaining good metabolic health in reducing the burden of gastrointestinal cancers, irrespective of genetic predisposition.

783Lifetime alcohol intake and stomach cancer risk: a pooled analysis of two prospective cohort studies

Abstract Background Alcohol consumption is causally linked to several cancer sites but the evidence for stomach cancer is still inconclusive. We aimed to quantify the association between alcohol intake and risk of stomach cancer, including subtypes. Methods We pooled data from two cohort studies including 452,958 individuals enrolled in the European Prospective Investigation into Cancer in 1992-98 and 38,756 Australians enrolled in the Melbourne Collaborative Cohort Study in 1990-94. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for incident stomach cancer were estimated using Cox regression. Results 1,225 incident stomach cancers were diagnosed over 7,094,637 person-years. Alcohol intake was not associated with overall stomach cancer risk. We observed a weak positive dose-response association for lifetime intake with non-cardia stomach cancer (HR = 1.03, 95% CI: 1.00-1.06/per 10 g/day increment), which is the more common type (77.6% of cases), and a weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) (phomogeneity=0.006). These associations did not differ appreciably by smoking or Helicobacter pylori infection status. Differences in HRs between diffuse-type and intestinal-type cancer were minimal (phomogeneity=0.97). HRs of 1.50 (95% CI: 1.12-2.01) for non-cardia and 0.53 (95% CI: 0.27-1.02) for cardia cancer were observed for a life course trajectory characterised by sustained heavy drinking compared with light drinking (phomogeneity=0.01). Conclusions Lifetime alcohol intake was associated with increased risk of non-cardia stomach cancer. The inverse association for cardia cancer indicates aetiologic differences between subsites. Key messages Limiting long-term alcohol consumption, and avoiding heavy use in particular, might be beneficial in preventing non-cardia stomach cancer.

Exploring the interactions between Helicobacter pylori (Hp) infection and other risk factors of gastric cancer: A pooled analysis in the Stomach cancer Pooling (StoP) Project.

Helicobacter pylori (Hp) is crucial in gastric carcinogenesis, but infection alone is not a sufficient cause, and the interaction between Hp infection and other risk factors has not been adequately studied. We conducted a pooled analysis of seven case-control studies from the Stomach cancer Pooling (StoP) Project, comprising 1377 cases and 2470 controls, to explore the interaction among Hp infection and tobacco smoking, alcohol drinking, socioeconomic status (SES) and dietary salt intake on the risk of gastric cancer. We estimated summary odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) by multivariate unconditional logistic regression. The analysis showed no consistent interaction between Hp infection and cigarette smoking, while interaction was more than multiplicative for alcohol drinking (OR=1.38, 95% CI: 1.07-1.77, P-interaction 0.02) and high intake of salt (OR=2.62, 95% CI: 1.88-3.65, P-interaction=0.04). The interaction with SES followed the multiplicative model (P=0.49), resulting in a weakening among infected individuals of the protective effect of high SES among observed Hp-negative individuals. The interactions found were more pronounced in subjects with history of peptic ulcer. The interactions with Hp infection were stronger for cigarette smoking and dietary salt in the case of noncardia cancer, and for alcohol and SES in the case of cardia cancer. No differences were found when stratifying for histologic type. This large-scale study aimed to quantify the interaction between Hp infection and other modifiable risk factors of gastric cancer revealed that the benefit of combined Hp eradication and lifestyle modification on gastric cancer prevention may be larger than commonly appreciated.

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.

Alterations of Gastric Microbiota in Gastric Cancer and Precancerous Stages.

ObjectiveMicrobial infections have been shown to contribute to gastric carcinogenesis, the knowledge of gastric microbiota alteration in this process may provide help in early diagnosis of gastric cancer. The aim of this study was to characterize the microbial changes and identify taxonomic biomarkers across stages of gastric carcinogenesis.MethodsThe gastric microbiota was investigated by 16S rRNA gene analysis in gastric mucosal specimens from 47 patients including superficial gastritis (SG), atrophic gastritis (AG), gastric intraepithelial neoplasia (GIN), and gastric cancer (GC). Differences in microbial composition across the disease stages, especially in GIN and GC were assessed using linear discriminant analysis effect size.ResultsThere was no gradual changing trend in the richness or diversity of the gastric microbiota across stages of gastric carcinogenesis. The relative abundance of dominant taxa at phylum and genus levels didn’t show a gradual shift pattern, and the only four taxa that continuously enriched from SG to GC were Slackia, Selenomonas, Bergeyella, and Capnocytophaga, all of which were oral bacteria. The most representative taxa which were enriched in GC patients were oral bacteria including Parvimonas, Eikenella and Prevotella-2, and environmental bacteria including Kroppenstedtia, Lentibacillus, and Oceanobacillus. The gastric microbiota in GIN patients were characterized by enrichment of intestinal commensals including Romboutsia, Fusicatenibacter, Prevotellaceae-Ga6A1-group, and Intestinimonas. Gastric cardia cancer and non-cardia cancer patients had significantly different microbiota profiles characterized by a higher abundance of Helicobacter in the cardia cancer patients.ConclusionsOur results provide insights on potential taxonomic biomarkers for gastric cancer and precancerous stages, and suggest that gastric microbiota might play different roles in the carcinogenesis of cardia cancer and non-cardia cancer.

Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer: A pooled analysis of data from two prospective cohort studies.

Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long‐term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group‐based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person‐years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person‐years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00‐1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08‐2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87‐1.00) was also observed. HRs of 1.48 (95% CI: 1.10‐1.99) for noncardia and 0.51 (95% CI: 0.26‐1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (P homogeneity = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences.

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.

Serum pepsinogen as a biomarker for gastric cancer: A nested case-control study using the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial data.

188 Background: Gastric cancer (GC) lacks specific symptoms, resulting in diagnosis at later stages and high mortality. Serum pepsinogen is a biomarker for atrophic gastritis, which is an intermittent phase in the development of GC. A serum based biomarker that indicates increased risk of GC would be useful for targeted prevention strategies. Methods: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a large randomized trial conducted over 10 centers in the US between 1993 and 2001. Serum samples were collected at baseline and participants were followed for development of incident GC. ELISA-based pepsinogen tests were conducted on pre-diagnostic serum samples of patients who developed GC and age, sex, and race-matched controls. Pepsinogen negative (PG-) and positive (PG+) status was determined using pepsinogen I (PGI) and pepsinogen I to II ratio (PGR). Those with PGR ≥ 3 and PGI &gt; 70µg/L were considered PG- while those with lower levels on either or both were considered PG+. Cox proportional hazard models were used to determine the hazard ratio (HR) and 95% confidence intervals (95%CI) of PG+ for GC. To examine the association of PG with non-cardia and cardia GC separately, propensity matching was used to create control subsets matched on age, sex, and race. Results: Pepsinogen test results were available on 105 GC cases (70 non-cardia and 35 cardia) and 220 matched controls. Median and range of time from pepsinogen measurement to incident GC diagnosis was 78.6 and 3.0-152.2 months, respectively. GC patients were more likely to be PG+ (31.4% vs 5.5%, p &lt; 0.001) and current smokers (20.0% vs 7.7%, p = 0.004) at baseline than controls. Compared to PG-, PG+ were at an increased risk of any GC (HR = 3.77; 95%CI = 2.50-5.71). After adjusting for family history of GC, smoking, and BMI, PG+ were still at a significantly increased risk of GC compared to PG- (adjusted HR = 4.42; 95%CI = 3.14-6.21). For 138 controls matched to 70 non-cardia cancers, PG+ were at an increased risk of non-cardia GC compared to PG- (HR = 5.65, 95%CI = 3.67-8.70; adjusted HR = 7.26, 95%CI = 4.84-10.90). For 70 controls matched to 35 cardia cancers, PG+ were not at greater risk of cardia GC compared to PG- (HR = 1.79, 95%CI = 0.72-4.44; adjusted HR = 1.95, 95%CI = 0.81-5.37). Conclusions: Pre-diagnostic serum pepsinogen levels from a large prospective cohort study predicted development of non-cardia GC but not cardia GC. PG could be considered as a potential risk biomarker to identify individuals at higher risk of non-cardia GC for targeted screening or interventions.

Alcohol Consumption and Risk of Gastric Cancer: The Japan Collaborative Cohort Study.

BackgroundAlcohol consumption is a potential risk factor for gastric cancer. However, findings from cohort studies that examined the relationship between alcohol consumption and gastric cancer risk among Japanese population are not conclusive.MethodsA total of 54,682 Japanese men and women participating in the Japan Collaborative Cohort study completed a questionnaire, including alcohol consumption information. The Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsAfter a median 13.4-year follow-up, we documented 801 men and 466 women incident cases of gastric cancer. Alcohol consumption was associated with increased risk of gastric cancer among men (HRs in ex-drinkers and current alcohol consumption of <23 g, 23–<46 g, 46–<69 g, and ≥69 g/d categories versus never drinkers were 1.82; 95% CI, 1.38–2.42, 1.41; 95% CI, 1.10–1.80, 1.47; 95% CI, 1.17–1.85, 1.88; 95% CI, 1.48–2.38, and 1.85; 95% CI, 1.35–2.53, respectively, and that for 10 g increment of alcohol consumption after excluding ex-drinkers was 1.07; 95% CI, 1.04–1.10). The association in men was observed for cardia and non-cardia gastric cancer (HRs in the highest alcohol consumption category versus never drinkers were 9.96; 95% CI, 2.22–44.67 for cardia cancer and 2.40; 95% CI, 1.64–3.52 for non-cardia cancer). However, no such trend was observed in women.ConclusionsAlcohol consumption is associated with increased risk of gastric cancer among Japanese men, regardless of anatomical subsite of the cancer.

Is cardia cancer a special type of gastric cancer? A differential analysis of early cardia cancer and non-cardia cancer.

Background: The prognosis of early cardia cancer and non-cardia cancer is still controversial. It is difficult to collect a large number of cases with complete information in clinical practice. Our study was aimed to identify the differences in clinicopathological characteristics and outcomes of early cardia gastric cancer and non-cardia gastric cancer.Methods: All cases analyzed were from Surveillance, Epidemiology, and End Results database. The data of the patients with early gastric cancer from 2004 to 2010 was retrospectively analyzed. Patients were distributed to cardia cancer group and non-cardia cancer group. Univariate and multivariate analyses were performed to examine differences between groups. The competitive risk model was made to compare the association with cardia cancer and non-cardia cancer about the causes of death. Propensity score matching (PSM) was performed to reduce the bias.Results: We found that cardia cancer was more common in male patients and the White than that in non-cardia cancer at early stage, signet ring cell carcinoma was more common in non-cardia cancer, and the differentiation of non-cardia cancer was worse. Univariate analysis showed that age, marital status, race, tumor location, histology, grade, stage, and operation or not can determine the prognosis. And the prognosis of patients with cardia cancer was worse than that of non-cardia cancer, according to lymph node metastasis and the depth of tumor invasion. Multivariate analysis showed cardia cancer was an independent prognostic factor for poor prognosis. After PSM, cardia cancer still exhibited poor prognosis.Conclusions: At early stage, cardia cancer had a poor prognosis compared with non-cardia cancer. The prevention and treatment of early cardia cancer need to be seriously treated.

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

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

Cancer risk among individuals of migrant origin in Belgium during the 2000s - Evidence of migration as a 'cancer risk transition'?

Recent research has shown a generally lower cancer risk and mortality among migrants from less-industrialised country origin. However, while rates are usually lower for 'lifestyle-related' cancers (e.g. breast, prostate, lung, colorectal), they are typically elevated for 'infection-related' ones such as liver and stomach cancer. Although these observations appear in line with the theory of 'migration as a rapid epidemiological transition', changes in cancer risk after migration have yet to be investigated, effectively testing if migration also entails a 'rapid cancer risk transition'. This study therefore examines cancer risk among migrants in Belgium, focusing on colorectal cancer as a typically lifestyle-related cancer on the one hand, and infection-related cancers on the other hand. We subdivide migrant groups of more and less industrialised country origin according to duration of stay, and calculate absolute and relative incidence rates between 2004 and 2013. Our findings corroborate the transition assumptions for men from Turkey and Morocco, but cannot support them for women. Italian male immigrants have an in-between position: their colorectal cancer risk does not differ from that of Belgian men, but infection-related and non-cardia stomach cancer risks are higher and remain so with longer duration of stay. The fact that rates for migrants from the Netherlands and France generally do not differ from those of Belgians further strengthens support for a cancer transition among male migrants. Further examinations should focus on changes in health-related behaviour that can explain persistently low colorectal cancer risks among Turkish and Moroccan migrants and can inform preventive strategies for other population subgroups. Knowledge about the higher non-cardia stomach cancer risk among Turkish, Moroccan, and Italian men can support early detection strategies by primary care providers when patients present with gastric symptoms, especially because this cancer tends to have unfavourable prognosis.