GC Risk Research Articles

Association of ANRIL Gene Polymorphisms with Gastric Cancer Risk: A Case-Control Study.

Background: Gastric cancer's (GC) cause is unknown, but its complexity indicates that, in addition to environmental factors, it may have genetic origins. Scientists are studying single-nucleotide polymorphisms (SNPs) in the antisense noncoding RNA in the INK4 locus (ANRIL) gene, which encodes a long noncoding RNA molecule. They found a link between the ANRIL gene product and some polymorphisms and GC, suggesting genetic changes may lead to precancerous conditions. Methods: In a case-control research that included 250 patients with GC and 210 controls who were age- and gender-matched, four SNPs within the ANRIL gene were genotyped. These SNPs were rs1333049, rs496892, rs2383207, and rs2151280. Tetra-primer amplification refractory mutation system-PCR was utilized to carry out the process of genotyping. Results: It was found that the chance of developing GC was connected with three SNPs rs2151280, rs1333049, and rs496892. Nevertheless, rs2383207 did not demonstrate any meaningful connection. In addition, whereas CCTC and TTCC haplotypes were shown to be less common, certain haplotypes that contained these SNPs (TTCG, TCTC, and TTTC) displayed a considerably higher prevalence in the cancer group in comparison to the control group. Conclusion: This study showed novel associations between specific ANRIL gene polymorphisms (SNPs) and the risk of GC. These findings shed light on the potential role of ANRIL SNPs in GC risk and highlight the need for additional research to clarify the underlying functional processes. Understanding these functional processes might lead to developing novel diagnostic or treatment approaches for this cancer.

One-carbon metabolism biomarkers and upper gastrointestinal cancer in the Golestan Cohort Study.

Incidence of esophageal and gastric cancer has been linked to low B-vitamin status. We conducted matched nested case-control studies of incident esophageal squamous cell carcinoma (ESCC; 340 case-control pairs) and gastric cancer (GC; 352 case-control pairs) within the Golestan Cohort Study. The primary exposure was plasma biomarkers: riboflavin and flavin mononucleotide (FMN) (vitamin B2), pyridoxal phosphate (PLP) (B6), cobalamin (B12), para-aminobenzoylglutamate (pABG) (folate), and total homocysteine (tHcy); and indicators for deficiency: 3-hydroxykyurenine-ratio (HK-r for vitamin B6) and methylmalonic acid (MMA for B12). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression adjusting for matching factors and potential confounders. High proportions of participants had low B-vitamin and high tHcy levels. None of the measured vitamin B levels was associated with the risk of ESCC and GC, but elevated level of MMA was marginally associated with ESCC (OR = 1.42, 95% CI = 0.99-2.04) and associated with GC (OR = 1.53, 95% CI = 1.05-2.22). Risk of GC was higher for the highest versus lowest quartile of HK-r (OR = 1.95, 95%CI = 1.19-3.21) and for elevated versus non-elevated HK-r level (OR = 1.59, 95% CI = 1.13-2.25). Risk of ESCC (OR = 2.81, 95% CI = 1.54-5.13) and gastric cancer (OR = 2.09, 95%CI = 1.17-3.73) was higher for the highest versus lowest quartile of tHcy. In conclusion, insufficient vitamin B12 was associated with higher risk of ESCC and GC, and insufficient vitamin B6 status was associated with higher risk of GC in this population with prevalent low plasma B-vitamin status. Higher level of tHcy, a global indicator of OCM function, was associated with higher risk of ESCC and GC.

Forty years of practice against gastric cancer in Linqu County, a high‐risk area of gastric cancer in China

AbstractGastric cancer (GC) is a global public health burden, with nearly one million new cases diagnosed each year worldwide. To investigate the risk factors and the prevention strategies for GC, in the past 40 years, a series of epidemiological studies have been carried out in Linqu County, Shandong Province, a high‐risk area of GC in China. Here, we briefly review the major efforts of 40‐year practices against GC in Linqu County, particularly highlighting a case‐control study to identify GC risk factors, a cohort study to determine the associations between the risk factors and the progression of gastric lesions, and an intervention trial to prevent GC development.

Higher frequency of gastric neoplasia in advanced chronic liver disease patients: Impact of screening endoscopy in an intermediate-high risk country

BackgroundThe Baveno VII guidelines were proposed to identify which patients could safely avoid screening esophagogastroduodenoscopy (EGD) for gastroesophageal varices. We aimed to evaluate the frequency of gastric neoplasia in compensated advanced chronic liver disease (cACLD) patients who underwent EGD for screening of gastroesophageal varices (GOEV) compared to a healthy population. MethodsRetrospective study that enrolled all cACLD patients who underwent EGD for GOEV screening (January 2008-June 2018) in a tertiary reference center. cACLD patients were compared with asymptomatic healthy individuals who underwent EGD in a private hospital setting (April 2017-March 2018). ResultsWe evaluated 1845 patients (481 cACLD patients, 1364 healthy individuals). A significantly higher frequency of gastric neoplasia was observed in patients with cACLD compared to healthy individuals (4.0% vs. 1.0 %; p < 0.001). Rare histopathological subtypes (WHO Classification) accounted for 28.7 % of gastric carcinoma cases in the cACLD cohort. Seven cases of gastric neoplasia (36.8 % of gastric neoplasia cases in the cACLD patients) were diagnosed in patients who, according to the Baveno VII criteria, would have not been submitted to EGD. ConclusionWe found an increased frequency of gastric neoplasia in patients with cACLD in comparison with healthy individuals. In countries with intermediate-high risk for GC, continuing to perform EGD could be beneficial.

Association between low-dose aspirin and the risk of gastric cancer and adenoma according to a family history of gastric cancer

This study aimed to evaluate the association between low-dose aspirin use and the risk of GC and gastric adenoma according to a family history of GC. We conducted a population-based study of 7,596,003 participants screened for GC between 2013 and 2014. Aspirin users and non-users were matched in a 1:1 ratio through propensity score matching (PSM). After PSM, 51,818 participants with a family history of GC and 359,840 without a family history of GC were analyzed (mean follow-up periods: 4.9 ± 0.8 and 4.8 ± 0.8 years, respectively). In patients with a family history of GC, aspirin use was significantly associated with a reduced risk of GC (adjusted hazard ratio [aHR]=0.80; 95 % confidence interval [CI]=0.65–0.995) and gastric adenoma (aHR=0.81; 95% CI=0.69–0.94). In those without a family history of GC, aspirin use was associated with a reduced risk of gastric adenoma (aHR = 0.92; 95 % CI = 0.86–0.98), but not with that of GC (aHR = 0.99; 95 % CI = 0.90–1.08). Low-dose aspirin use was associated with a reduced risk of gastric adenoma, regardless of a family history of GC, and may play a role in the early stages of gastric carcinogenesis. However, the association between aspirin and GC was only observed in those with a family history of GC.

Association between menopausal hormone therapy and the risk of gastric cancer: A Korean nationwide population-based cohort study

ObjectiveGastric cancer (GC) is more common in men than women, but also more common among postmenopausal than premenopausal women. The protective effect of reproductive hormones against GC remains unclear. Therefore, we evaluated the association between menopausal hormone therapy (MHT) and the risk of GC in women. MethodsWe investigated the national cohort data of women aged over 40 years who underwent health checkups by the Korean National Health Insurance Service in 2009. After excluding individuals with missing data and those previously diagnosed with cancer, 1,354,621 postmenopausal women were included and divided into groups according to their MHT history. We followed the study population until 2018 and analyzed the hazard ratios (HR) with 95 % confidence intervals (CIs) for the incidence rate of GC in a multivariate adjusted model. ResultsThe number of women with and without a history of MHT was 214,723 (15.9 %) and 1,139,898 (84.1 %), respectively. During the mean 8.32 ± 0.8 years of follow-up, a total of 12,496 GC cases developed in the study population (10,962 MHT non-users; 1534 MHT users). In the adjusted model, MHT was associated with a 12 % decrease in the development of GC relative to non-use of MHT (HR 0.88; 95 % CI 0.83–0.93). Exposure to MHT for >2 years was linked to a reduction in GC risk, particularly when initiated before the age of 50, giving a 45 % risk reduction. ConclusionsAccording to our large-scale prospective national cohort study, exogenous MHT is associated with a decreased risk of GC in postmenopausal women.

Development of a gastric cancer risk calculator for questionnaire-based surveillance of Iranian dyspeptic patients

BackgroundGastric cancer (GC) is considered a silent killer, taking more than three quarters of a million lives annually. Therefore, prior to further costly and invasive diagnostic approaches, an initial GC risk screening is desperately in demand.MethodsIn order to develop a simple risk scoring system, the demographic and lifestyle indices from 858 GC and 1132 non-ulcer dyspeptic (NUD) patients were analysed. We applied a multivariate logistic regression approach to identify the association between our target predictors and GC versus NUD. The model performance in classification was assessed by receiver operating characteristic (ROC) analysis. Our questionnaire covering 64 predictors, included known risk factors, such as demographic features, dietary habits, self-reported medical status, narcotics use, and SES indicators.ResultsOur model segregated GC from NUD patients with the sensitivity, specificity, and accuracy rates of 85.89, 63.9, and 73.03%, respectively, which was confirmed in the development dataset (AUC equal to 86.37%, P < 0.0001). Predictors which contributed most to our GC risk calculator, based on risk scores (RS) and shared percentages (SP), included: 1) older age group [> 70 (RS:+ 241, SP:7.23), 60–70 (RS:+ 221, SP:6.60), 50–60 (RS:+ 134, SP:4.02), 2) history of gastrointestinal cancers (RS:+ 173, SP:5.19), 3) male gender (RS:+ 119, SP:3.55), 4) non-Fars ethnicity (RS:+ 89, SP:2.66), 5) illiteracy of both parents (RS:+ 78, SP:2.38), 6) rural residence (RS:+ 77, SP:2.3), and modifiable dietary behaviors (RS:+ 32 to + 53, SP:0.96 to 1.58).ConclusionOur developed risk calculator provides a primary screening step, prior to the subsequent costly and invasive measures. Furthermore, public awareness regarding modifiable risk predictors may encourage and promote lifestyle adjustments and healthy behaviours.

Association of PTGER4 and PRKAA1 genetic polymorphisms with gastric cancer

BackgroundGastric cancer (GC) is one of the most common malignancies, affected by several genetic loci in the clinical phenotype. This study aimed to determine the association between PTGER4 and PRKAA1 gene polymorphisms and the risk of GC.MethodsA total of 509 GC patients and 507 age and sex-matched healthy controls were recruited to explore the association between PTGER4 and PRKAA1 genetic polymorphisms and GC susceptibility. Logistic regression analysis was used to study the correlation between these SNPs and GC, with odd ratio (OR) and 95% confidence interval (CI) as indicators. Multifactor dimensionality reduction was utilized to analyze the genetic relationships among SNPs. was conducted to predict gene expression, the impact of SNPs on gene expression, and the signaling pathways involved in PTGER4 and PRKAA1.ResultsOverall, rs10036575 in PTGER4 (OR = 0.82, p = 0.029), rs10074991 (OR = 0.82, p = 0.024) and rs13361707 (OR = 0.82, p = 0.030) in PRKAA1 were associated with susceptibility to GC. Stratification analysis revealed that the effects of these SNPs in PTGER4 and PRKAA1 on GC susceptibility were dependent on smoking and were associated with a reduced risk of adenocarcinoma (p < 0.05). Bioinformatics analysis showed an association between SNPs and corresponding gene expression (p < 0.05), and PRKAA1 may affect GC by mediating RhoA.ConclusionThis study suggests that PTGER4 and PRKAA1 SNPs might affect the susceptibility of GC, providing a new biological perspective for GC risk assessment, pathogenesis exploration, and personalized treatment.

CDH1 incidental findings in patients with personal or family history of breast cancer.

10524 Background: Pathogenic variants in CDH1 ( CDH1+) are associated with hereditary diffuse gastric cancer (HDGC), with an increased risk for DGC (~40-83%) and lobular breast cancer (BC) (~64%) [1]. The National Cancer Center Network recommends the inclusion of CDH1 in multi-gene panel testing (MGPT) for patients with significant history of BC, given its classification as a high-risk BC gene [2]. Management includes prophylactic gastrectomy or consideration of annual endoscopic biopsies and high-risk breast screening, with consideration of prophylactic mastectomy. Several studies have identified CD H1+ patients who do not meet the International Gastric Linkage Consortium’s diagnostic criteria for HDGC [3.4,5,6]. These studies have brought concerns of CDH1 pathogenic variants in patients with low risk phenotypes, given the potential for total gastrectomy to reduce DGC risk. Our study aims to investigate our cohort of patients with a personal and/or family history of BC to determine if there is a significant number of CDH1+ patients with a non-classical presentation of HDGC. Methods: 17,208 families with a history of BC who underwent MGPT were seen in a Clinical Cancer Genetics (CCG) high-risk breast clinic between August 2013 and July 2022. They were identified using a prospectively maintained MD Anderson Cancer Center CCG database. Families were categorized by their history of GC and CDH1 status. Results: Among the families, 10,202 (59%) had a proband with a personal history of BC, with a mean age of onset of 51 years. 49 families (0.28%) were CDH1+. 21 CDH1+ families (43%) had no personal and/or family history of GC. Overall, 0.12% of families within the cohort were CDH1+ and had no family history of GC. A chi-square goodness of fit test was performed comparing observed (O) versus expected frequencies (E) (O/E) of families that were: 1) CDH1+ and had a history of GC (28/28), 2) CDH1+ and no history of GC (21/21), 3) CDH1 – (benign variant or variant of unknown significance (VUS)) and a history of GC (180/164), and 4) CDH1- and no history of GC (16,979/16,995). O was determined by using a general population risk of GC (0.81%) and estimated risk of DGC for CDH1+ individuals (58.2%). The X2 was determined to be 1.576, with a p-value of 0.66483. Conclusions: In comparison to the expected frequency of incidental CDH1+ families identified via MGPT, we found that there was not a significant difference in expected and observed frequencies of families based on CDH1 status and presence of GC. These results likely reflect the incomplete penetrance and variable expressivity of HDGC, in addition to reported cases of occult signet ring cell carcinomas in biopsy samples or surgical pathology that has been reported in low risk presenting families [7]. We seek to validate these results with cohort of patients in which the diffuse gastric cancer pathology is known and to expand the analysis in patients specifically with a personal history of lobular breast cancer.

MP44-17 USE OF DECIPHER PROSTATE BIOPSY TEST IN MEN WITH FAVORABLE RISK DISEASE UNDERGOING CONSERVATIVE MANAGEMENT IN THE SEER REGISTRY

You have accessJournal of UrologyCME1 Apr 2023MP44-17 USE OF DECIPHER PROSTATE BIOPSY TEST IN MEN WITH FAVORABLE RISK DISEASE UNDERGOING CONSERVATIVE MANAGEMENT IN THE SEER REGISTRY Alec Zhu, Ashwin Ramaswamy, James Proudfoot, Ashley Ross, Yang Liu, Elai Davicioni, Nicholas Zaorsky, Angela Jia, Daniel Spratt, Edward Schaeffer, Valentina Petkov, and Jim Hu Alec ZhuAlec Zhu More articles by this author , Ashwin RamaswamyAshwin Ramaswamy More articles by this author , James ProudfootJames Proudfoot More articles by this author , Ashley RossAshley Ross More articles by this author , Yang LiuYang Liu More articles by this author , Elai DavicioniElai Davicioni More articles by this author , Nicholas ZaorskyNicholas Zaorsky More articles by this author , Angela JiaAngela Jia More articles by this author , Daniel SprattDaniel Spratt More articles by this author , Edward SchaefferEdward Schaeffer More articles by this author , Valentina PetkovValentina Petkov More articles by this author , and Jim HuJim Hu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003290.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The Surveillance, Epidemiology, and End Results (SEER) cancer registry was linked to the Decipher 22-gene expression classifier (GC) for men with prostate cancer (PCa). We examined the use of conservative management (active surveillance/watchful waiting) for GC tested and untested men and assessed factors associated with adverse pathology (AP; grade group ≥3, pathological stage ≥pT3b, or lymph node invasion) at radical prostatectomy (RP). METHODS: Men in the registry diagnosed with favorable risk (grade group [GG] 1 and 2) PCa from 2016 to 2018 were linked to data from GC testing conducted between 2016 to 2020 (Veracyte, San Diego, CA). GC scores (range 0-1) and GC risk groups (low, intermediate, and high) were used for continuous and categorical analyses. Multivariable logistic regressions quantified the association of GC test results with conservative management as well as the association of GC test results with AP at RP in comparison to tumor volume as measured by the percentage of positive cores with cancer (PPC). RESULTS: A total of 100,279 men were evaluated (2,889 tested with GC at biopsy and 97,390 untested). Overall, conservative management increased from 20% to 23% and 33% to 37% from 2016 to 2018 in the untested and tested populations, respectively. In men aged <70 years, conservative management increased from 20% to 24% and 35% to 37% from 2016 to 2018 in the untested and tested populations, respectively. In adjusted analyses, GC testing was significantly associated with greater odds of conservative management (OR [95% CI] 2.1 [1.9-2.4], p<0.001). Conservative management use was highest for GC low risk men (41%) as compared to intermediate (31%) or high (16%) GC risk men. Higher GC and PPC were associated with RP surgery; but for men treated with RP, only higher GC was significantly associated with adverse pathology (Figure 1). CONCLUSIONS: GC testing was independently associated with a two-fold increase in conservative management utilization for favorable risk disease. Men with lower GC scores were more likely to undergo conservative management. Both higher GC scores and tumor volume (as measured by PPC) were associated with increased likelihood of RP. Higher GC was significantly associated with a higher likelihood of AP at time of RP, while higher tumor volume was not. Source of Funding: There was no direct funding from an outside organization or sponsor © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e618 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alec Zhu More articles by this author Ashwin Ramaswamy More articles by this author James Proudfoot More articles by this author Ashley Ross More articles by this author Yang Liu More articles by this author Elai Davicioni More articles by this author Nicholas Zaorsky More articles by this author Angela Jia More articles by this author Daniel Spratt More articles by this author Edward Schaeffer More articles by this author Valentina Petkov More articles by this author Jim Hu More articles by this author Expand All Advertisement PDF downloadLoading ...

Association between Age at Helicobacter pylori Eradication and the Risk of Gastric Cancer Stratified by Family History of Gastric Cancer: A Nationwide Population-Based Study

This study compares the risk of GC according to age at H. pylori eradication, stratified based on the presence of family history of GC using a population-based large cohort. We analyzed individuals who underwent GC screening between 2013 and 2014 and received H. pylori eradication therapy before screening. Among 1,888,815 H. pylori-treated patients, 2610/294,706 and 9332/1,594,109 patients with and without a family history of GC, respectively, developed GC. After adjusting for confounders, including age at screening, the adjusted hazard ratios (95% confidence intervals) for GC comparison, 70-74, 65-69, 60-64, 55-59, 50-54, 45-49, and <45 years with ≥75 years at H. pylori eradication were 0.98 (0.79-1.21), 0.88 (0.74-1.05), 0.76 (0.59-0.99), 0.62 (0.44-0.88), 0.57 (0.36-0.90), 0.38 (0.22-0.66), and 0.34 (0.17-0.67), respectively, among patients with a family history of GC (p < 0.001) and 1.01 (0.91-1.13), 0.95 (0.86-1.04), 0.86 (0.75-0.98), 0.67 (0.56-0.81), 0.56 (0.44-0.71), 0.51 (0.38-0.68), and 0.33 (0.23-0.47), respectively, among patients without a family history of GC (p < 0.001). In patients with and without a family history of GC, young age at H. pylori eradication was significantly associated with a reduced risk of GC, suggesting that the early treatment of H. pylori infection can maximize GC prevention.

Study on TFF1 and PALB2 gene variants associated with gastric carcinoma risk in the Chinese Han population

ObjectiveGastric carcinoma (GC) has received extensive attention due to its complex pathogenesis. Studies have shown that the expression of Trefoil factor 1 (TFF1) and Partner and localiser of BRCA2 (PALB2) genes promotes the occurrence of GC. Therefore, we investigated whether TFF1 and PALB2 gene polymorphisms are associated with GC risk in the Chinese Han population. MethodsA total of 509 GC cases and 505 controls were recruited, and single nucleotide polymorphisms (SNPs) of TFF1 and PALB2 in these subjects were genotyped. The association between each candidate polymorphism and GC risk was assessed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). The visualization of gene-gene interactions and functional enrichment analysis were then performed using Cytoscape software and the R package “cluster profile”. ResultsThe TFF1 rs2156310 polymorphism significantly reduced the predisposition to GC in people under 60 years of age (AA vs. AG - GG, OR = 0.58, 95% CI = 0.35–0.97, p = 0.036). The gender-stratified analysis found that PALB2 rs513313 was significantly associated with the risk of GC in males (CT vs. TT, OR = 1.51, 95% CI = 1.06–2.15, p = 0.022). Besides, PALB2 rs249954 significantly reduced the susceptibility to GC in females (AA vs GG, OR = 0.42, 95% CI = 0.19–0.94, p = 0.034). ConclusionOur results revealed that TFF1 and PALB2 gene polymorphisms were correlated with the genetic susceptibility to GC, providing certain data support for researchers to further study the mechanism of GC.

Selected Articles from This Issue

Colorectal cancer (CRC) screening has proven to be very effective in preventing this deadly disease. However, effectiveness can be improved, and costs can be reduced by using additional biomarkers for candidate selection. Arnau-Collell and colleagues developed a polygenic risk score and evaluated its effectiveness in determining which individuals should undergo a colonoscopy after a positive FIT result considering their CRC-associated genetic risk. The study highlights the potential application of these variants when applied to stratify people at a higher risk of CRC in the context of screening programs, while underlining the need to incorporate additional biomarkers.Breast cancer incidence is greater among non-Hispanic White and Black women compared to other women. In a large population-based study, Barnard and colleagues observed that the distributions of two breast cancer risk factors, body mass index (BMI) and mammographic density (MD) varied dramatically by race and ethnicity, with the highest MD among Asian women and the highest BMI among Native Hawaiian and Pacific Islander women. Magnitudes of association between BMI and MD did not vary by race or ethnicity. Future efforts to reduce breast cancer incidence should consider the distributions of breast cancer risk factors to ensure equitable prevention strategies.Gastric cancer (GC) has a particularly high mortality rate in the US, as it lacks specific symptoms resulting in diagnosis at later stages. In and colleagues conducted a nested case-control study within the PLCO Screening Trial to examine the utility of pepsinogen as a predictor of incident GC. The authors found that pre-diagnostic pepsinogen sero-positivity was associated with 8.5-fold increased risk for GC. This suggests that despite the overall low incidence of GC in the US, serum pepsinogen holds potential to be used as biomarker to identify individuals at higher risk of GC for US-based targeted screening or interventions. 5-alpha reductase inhibitors (5-ARIs) are common medications among older men with benign prostatic hyperplasia. Conflicting results on 5-ARIs and prostate cancer mortality have led to debate about its effectiveness in primary chemoprevention. Vaselkiv and colleagues studied 38,000 men followed for 20 years and detailed information on screening and healthcare use. In the setting of regular screening, 5-ARI use was not associated with increased prostate cancer mortality, while it lowered risk of low-grade cancers. These findings together with those from other cohorts highlight the importance of framing risks and benefits of 5-ARIs in the context of real-world data and in light of the importance of clinical follow-up of men on 5-ARIs.

Autoimmune gastritis: long-term natural history in naïve Helicobacter pylori-negative patients

ObjectiveAutoimmune gastritis (AIG) is an immunomediated disease targeting parietal cells, eventually resulting in oxyntic-restricted atrophy. This long-term follow-up study aimed at elucidating the natural history, histological phenotype(s), and associated cancer...

Abstract 2274: Identification of predisposition and progression gastric cancer biomarkers in Latinos

Abstract Gastric cancer (GC) disproportionally affects people of Latino ancestry and represent a leading cause of incidence and mortality disparities in this minority populations. When compared to Non-Latino Whites, Latinos are ~2-fold more likely to be diagnosed with and to die of GC. The goal of our research program is to contribute to GC research in patients of Latino ancestry and advance cancer health disparity research. One of the research projects aims at identifying germline variants associated with GC risk. To do so, we are identifying novel gastric cancer genes and detecting mutations in previously reported GC genes, using whole-exome sequencing, in 500 patients who have been diagnosed with early-onset GC and/or who had GC and family history of cancer. Whole exome sequence data collection was recently completed and is being analyzed with the primary goals of estimating the prevalence and penetrance in known cancer genes as well as the identification of new GC genes. Using in-house exome data and publicly available genetic data, we will identify variants with predicted impact in the phenotype to design a panel that will be used for their detection in gastric preneoplasia biopsies. These variants will be tested using duplex sequencing, a highly sensitive method that can detect very rare mutations with ultra-depth sequencing. We will then select the variants with likely functional consequences for tumor initiation and/or progression to generate isogenic gastric organoids to investigate their effect in proliferation, differentiation, and gene expression. We aim to generate a body of work that can be used for risk assessment, prevention, early diagnostic, and that will lead to better outcomes for GC in this important U.S. minority. Dr. Ana Estrada-Florez is the recipient of the AACR Cancer Health Disparities Fellowship. Citation Format: Ana Patricia Estrada-Florez, Paul Lott, Ted Toal, Nicole Halmai, Elizabeth Quino, Alma Poceros-Coba, Alix Guevara, Fabian Castro, Jhon Suarez, John Mcpherson, Rasika Venkatesh, Hongyong Zhang, Apri Vang, Guadalupe Polanco, Joana Guerra, Graciela Molina, Carol Parra, Adriana Della Valle, Esteban Castelao, Manuel Teixeira, Mabel Bohorquez, Javier Torres, Alejandro Carvajal Corvalan, Luis G. Carvajal-Carmona. Identification of predisposition and progression gastric cancer biomarkers in Latinos [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 2274.

The LEGACy study: a European and Latin American consortium to identify risk factors and molecular phenotypes in gastric cancer to improve prevention strategies and personalized clinical decision making globally

BackgroundGastric Cancer (GC) is the fourth most deadly cancer worldwide. Enhanced understanding of its key epidemiological and molecular drivers is urgently needed to lower the incidence and improve outcomes. Furthermore, tumor biology in European (EU) and Latin American (LATAM) countries is understudied. The LEGACy study is a Horizon 2020 funded multi-institutional research approach to 1) detail the epidemiological features including risk factors of GC in current time and 2) develop cost-effective methods to identify and integrate biological biomarkers needed to guide diagnostic and therapeutic approaches with the aim of filling the knowledge gap on GC in these areas.MethodsThis observational study has three parts that are conducted in parallel during 2019–2023 across recruiting centers from four EU and four LATAM countries: Part 1) A case-control study (800 cases and 800 controls) using questionnaires on candidate risk factors for GC, which will be correlated with clinical, demographic and epidemiological parameters. Part 2) A case-control tissue sampling study (400 cases and 400 controls) using proteome, genome, microbiome and immune analyses to characterize advanced (stage III and IV) GC. Patients in this part of the study will be followed over time to observe clinical outcomes. The first half of samples will be used as training cohort to identify the most relevant risk factors and biomarkers, which will be selected to propose cost-effective diagnostic and predictive methods that will be validated with the second half of samples. Part 3) An educational study, as part of our prevention strategy (subjects recruited from the general public) to test and disseminate knowledge on GC risk factors and symptoms by a questionnaire and informative video. Patients could be recruited for more than one of the three LEGACy studies.DiscussionThe LEGACy study aims to generate novel, in-depth knowledge on the tumor biological characteristics through integrating epidemiological, multi-omics and clinical data from GC patients at an EU-LATAM partnership. During the study, cost-effective panels with potential use in clinical decision making will be developed and validated.Trial registrationClinicalTrials.gov Identifiers:Part 1: NCT03957031.Part 2: NCT04015466.Part 3: NCT04019808.

Association of single nucleotide polymorphisms (SNPs) with gastric cancer susceptibility and prognosis in population in Wuwei, Gansu, China

BackgroundGastric cancer (GC) is the sixth most common cancer. China is one of the most frequent GC occurred countries, and Wuwei, Gansu, is one of the highest incidence area in China. Possible biomarkers of GC susceptibility and prognosis among the population in Wuwei are urgently needed.MethodsAll participants in this study were recruited from the Wuwei Cancer Hospital in Gansu, including 303 patients diagnosed with GC and 200 non-cancer controls. DNA was extracted for further single nucleotide polymorphisms (SNP) genotyping. All SNPs were firstly screened by additive logistic regression model then selected SNPs were subjected to univariate Cox regression analysis and multivariate Cox regression analysis for their associations with GC occurrence.ResultsThe results showed that 31 SNPs were significantly related to the incidence of GC in Wuwei, Gansu, China. Genotype rs4823921 was significantly related to the overall survival of GC patients and AC/AA genotype of rs4823921 polymorphism was significantly associated with an increased risk of GC in Wuwei population.ConclusionsThirty-one SNPs were significantly related to the incidence of GC in Wuwei and rs4823921 genotype AC/AA was significantly associated with poor prognosis of GC patients in Wuwei, Gansu.

Meat consumption and risk of esophageal and gastric cancer in the Golestan Cohort Study, Iran.

Red meat and processed meat are associated with some gastrointestinal cancers. Our study aims to investigate the association of different meat types with esophageal and gastric cancer (EC, GC) in a high‐risk population. The Golestan Cohort Study (GCS) is a population‐based cohort of 50 045 individuals aged 40 to 75 from northeast Iran. Detailed data on different exposures were collected using validated questionnaires. We considered quintiles of meat consumption, using grams and density (g/1000 kcal/day). We calculated intake of red, processed, organ and white meat, as well as total red meat, including the first three. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the association between meat types and cancer. During 12 years of follow‐up, out of 49 585 participants (57.4% women), 369 developed EC (48.2% women) and 368 developed GC (27.5% women), including 309 esophageal squamous cell, 20 esophageal adenocarcinomas, 216 cardia and 95 non‐cardia GC. No association was found for EC except for red meat among females (HR for one quintile increase 1.13, 95% CI = 1.00‐1.27). The risk of GC increased for intake of total red meat (HR 1.08, 95% CI = 1.00‐1.17) and red meat separately (HR 1.09, 95% CI = 1.00‐1.18). The HR for red meat and non‐cardia GC was 1.23 (95% CI = 1.02‐1.48). No associations were observed for other types of meat. In conclusion, in this high‐risk population red meat intake is associated with GC, but not EC, suggesting a substantial role of this modifiable factor in determining the burden of GC.

A Systematic Review of Decipher Genomic Classifier Risk Scores for Prostate Cancer in African-Americans

Background: Prostate Cancer (PCa) is a non-cutaneous malignancy in men, and Decipher being a genomic test, has gained increasing attention in estimating the risk of developing a recurrence or metastatic PCa disease in patients. Therefore, this study is focused on evaluating the association of Decipher score risk with recurrence of prostate cancer patients based on their medical, genetic predictors, and demographics (e.g., races) by conducting a systematic review. Moreover, the study has also assessed whether Decipher score risk can be a good predictor for prostate patients’ metastasis and prostate cancer-specific mortality in men and clinical decision-making regarding patient treatment recommendations. Methods:: The research study has reviewed 74 research articles, and the systematic review results have been presented in the form of themes. The studies' review indicated that Decipher acts as a genomic metastasis signature to predict metastatic disease among patients and make better decisions about treating the disease. Moreover, this genomic test can also be used in conjunction with Magnetic Resonance Imaging (MRI) for identifying the lesions that may carry the biological potential for early metastases. Furthermore, this review also identified that treatment options for PCa might range from Adjuvant Radiation Treatment (ART) and Salvage Radiation Therapy (SRT) to Radical Prostatectomy (RP); however, the selection of treatment methodology depends upon the GC score and risk stratification. Results: The results further suggested that the occurrence of PCa is two folds greater among African- Americans (AA) men as compared to non-AA men. Thus, the increasing incidence of PCa among AA and discrimination within AA's health and socio-economic conditions plays a significant role in treating AA. In this scenario, the Decipher test score plays an essential role in making treatment decisions. Conclusion: To conclude, further trials are still required for validating the Decipher biomarkers, and scientists should enhance the decipher test ability to be run on a patient's blood samples instead of tumor tissue, which will help patients use decipher as a screening test at the asymptomatic level.

The Single-Nucleotide Polymorphism of miR-27a rs895819 and the Expression of miR-27a in Helicobacter pylori-Related Diseases and the Correlation with the Traditional Chinese Medicine Syndrome.

Aims The study aims to explore the effects of the single-nucleotide polymorphism of miR-27a and its expression in Helicobacter pylori (H. pylori)-related diseases and the relationship between gastric pathology and traditional Chinese medicine (TCM). Methods Subjects were classified into six histopathological groups and five TCM syndrome groups. All specimens underwent H. pylori detection through rapid urease test and methylene blue staining. Histopathological characteristics were observed by hematoxylin-eosin. The expression of miR-27a and its genotype were, respectively, detected by Quantitative Real-Time PCR and direct sequencing. Results H. pylori promoted the malignant evolution of gastric mucosa and were involved in the formation of TCM syndrome. In H. pylori-positive patients, the frequency of miR-27a CT genotype at the rs895819 locus and its expression in the gastric cancer group were higher than those in other pathological groups. TCM syndrome had a close relationship with histopathological changes, and patients with spleen-qi deficiency syndrome had a higher risk of gastric cancer than other syndromes, regardless of H. pylori infection. Conclusion The C allele at miR-27a rs895819 locus may be an oncogene in gastric cancer. High levels of miR-27a could play an important role in gastric malignant evolution, especially cancerization. There is a certain connection between TCM syndrome and pathological changes of the gastric mucosa to some extent, where patients with SQD syndrome had a higher risk of GC.