Tram Kim Lam

Gastric cancer remains a major health challenge globally. In the United States, gastric cancer outcomes remain poor, with well-documented disparities in incidence and mortality. In 2024, the US National Cancer Institute convened a Think Tank on Advancing Gastric Cancer Prevention, with participation of over 200 global leaders from academia, clinical practice, and industry as well as patient advocates to exchange knowledge, lived experiences, and discuss future research opportunities. This commentary summarizes the Think Tank presentations and discussions of key existing evidence as well as challenges and opportunities for the prevention and control of this preventable disease. Primary prevention discussions focused on the use of the screen-and-treat strategy for Helicobacter pylori eradication. Secondary prevention discussions included endoscopic screening and surveillance of advanced gastric precancerous lesions. Primary conclusions for gastric cancer prevention and control included the need for (1) developing large-scale study resources that optimize the ability to conduct research with potential clinical translation applications; (2) strengthening and building community-public health-academic partnerships to enhance research; and (3) leveraging evidence-based strategies developed in high-risk East Asian countries to high-risk subgroups in low- and moderate-risk countries including the United States. There was overwhelming agreement that given the current state of gastric cancer incidence and survival in the United States, novel strategies to control the carcinogenic effects of H. pylori and to improve detection of precursors are the key to substantially reducing the burden of this disease.

Background and Aims: This large-scale, population-based cohort study examined the associations between metabolic syndrome and cholangiocarcinoma risk, including its intrahepatic and extrahepatic forms. Approach and Results: A total of 4,932,211 adults aged ≥40 years participated in a government-initiated health checkup program (2012–2017), which collected lifestyle data, anthropometric measurements, and biochemical tests. Follow-up continued until 2021, with data linkage to National Cancer and Death Registries to ascertain the occurrence of cholangiocarcinoma and obtain vital status information. Fine and Gray models accounted for competing risks. During 35,879,371 person-years of follow-up, 6117 cholangiocarcinoma cases were identified, with an incidence rate of 17.05 (95% CI: 15.90–18.20) per 100,000 person-years. Individuals with metabolic syndrome had significantly higher incidences of both intrahepatic and extrahepatic cholangiocarcinoma ( p p for trend <0.0001). Conclusions: The positive association between metabolic syndrome and cholangiocarcinoma risk suggests that managing metabolic risk factors might reduce the occurrence of both intrahepatic and extrahepatic cholangiocarcinoma.

The current body of evidence from both preclinical and epidemiologic studies suggests that cumulative stress may play a role in carcinogenesis; however, few studies on human populations have examined allostatic load (AL) as it relates to cancer risk, progression, and mortality. In this commentary, we discuss the use and value of AL as a measure to assess exposure to stress for cancer epidemiologic studies, describe the existing evidence between AL and sources of cancer-related environmental stressors, and summarize the existing epidemiologic studies on AL and cancer risk, progression, and mortality. We also outline several knowledge gaps and what steps should be considered to advance research on the role of AL and cancer risk, progression, and mortality in human populations.

This report provides a summary of the identified evidence gaps and a general discussion of the next steps to advance cancer epidemiology research in Hispanic/Latino (H/L) populations based partly on the workshop, “Cancer Epidemiology in Hispanic Populations,” convened by the NCI in September 2021. The cancer burden among H/L populations varies greatly by nativity and country of origin, yet this variation is not often captured due to systemic challenges in how racial/ethnic data have been collected and often reported in aggregate for this heterogeneous population. Developing culturally relevant assessment tools, increasing the representation of H/L participants, and adopting appropriate methodologic approaches are critical to enhancing cancer research. There is a variety of current funding mechanisms that may be used to address these evidence gaps and priorities, including investigator-initiated mechanisms. Cancer epidemiologic research in H/L populations should leverage existing resources where possible. New and ongoing studies should collect information on nativity status, country of origin, and related measures, use culturally specific assessment tools, engage in collaborative science, and maintain strong community engagement to build studies that will meaningfully address the cancer burden experienced by the growing H/L population.

With the escalating prevalence of obesity, the association between obesity and cancer is a growing public health concern. Obesity will soon surpass tobacco smoking as the most important preventable cause of cancer. Obesity-driven mechanisms can alter cell functions to induce metabolic changes, chronic inflammation, and insulin resistance that are believed to contribute to cancer risk and development; yet the specific underlying biological mechanisms of obesity-related cancer development are largely unknown. The Metabolic Dysregulation and Cancer Risk Program: a transdisciplinary approach to obesity-associated cancers (MeDOC) is a trans–National Cancer Institute research initiative supported by the Division of Cancer Control and Population Sciences, the Division of Cancer Biology, the Division of Cancer Prevention, and the Center to Reduce Cancer Health Disparities. The overall purpose of the MeDOC Program is to advance our understanding of the underlying mechanisms that connect obesity, metabolic dysregulation, and increased obesity cancer risk as well as identify markers that will enhance cancer risk prediction, improve screening for high-risk individuals, and identify targets for preventive and therapeutic interventions for cancer interception or treatment. This report describes the funded research projects, the Coordinating Center, and the goals of the MeDOC program.

Background: More than 62 million people self-identified as Hispanic/Latino (H/L) in the 2020 United States census. The U.S. H/L population has higher burden of certain cancers compared with their non-Hispanic White counterparts. Methods: Key term search using the NIH Query/View/Report (QVR) system, along with Research, Condition, and Disease Categorization codes identified cancer epidemiology research grants in H/L populations funded by the NCI as a primary or secondary funder from fiscal years 2016 through 2021. Three reviewers identified eligible grants based on specified inclusion/exclusion criteria and a codebook for consistency extracting key characteristics. Results: A total of 450 grants were identified through the QVR system using key words related to H/Ls; 41 cancer epidemiology grants remained after applying exclusion criteria. These grants contained specific aims focused on H/Ls (32%) or included H/Ls as part of a racial/ethnic comparison (68%). NCI was the primary funder of the majority of the grants (85%), and most of the research grants focused on cancer etiology (44%) and/or survivorship (49%). Few grants (10%) investigated environmental exposures. Conclusions: This article provides an overview of NCI-funded cancer epidemiology research in H/L populations from 2016 to 2021. Future cancer epidemiology research should reflect the changing dynamics of the U.S. demography with diverse, representative populations and well-characterized ethnicity. Impact: Research that carefully measures the relevant biological, environmental, behavioral, psychologic, sociocultural, and clinical risk factors will be critical to better understanding the nuanced patterns influencing cancer-related outcomes in the heterogenous H/L population.

Background: Chronic hepatitis C virus (HCV) infection can affect immune response and inflammatory pathways, leading to severe liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Methods: In a prospective cohort of chronically HCV-infected individuals, we sampled 68 individuals who developed cirrhosis, 91 controls who did not develop cirrhosis, and 94 individuals who developed HCC. Unconditional odds ratios (ORs) from polytomous logistic regression models and canonical discriminant analyses (CDAs) were used to compare categorical (C) baseline plasma levels for 102 markers in individuals who developed cirrhosis vs. controls and those who developed HCC vs. cirrhosis. Leave-one-out cross validation was used to produce receiver operating characteristic curves to assess predictive ability of markers. Lastly, biological pathways were assessed in association with cirrhotic development compared to controls. Results: After multivariable adjustment, DEFA-1 (OR: C2v.C1 = 7.73; p < 0.0001), ITGAM (OR: C2v.C1 = 4.03; p = 0.0002), SCF (OR: C4v.C1 = 0.19; p-trend = 0.0001), and CCL11 (OR: C4v.C1 = 0.31; p-trend= 0.002) were all associated with development of cirrhosis compared to controls; these markers, together with clinical/demographics variables, improved prediction of cirrhosis from 55.7% (in clinical/demographic-only model) to 74.9% accuracy. A twelve-marker model based on CDA results further increased prediction of cirrhosis to 88.0%. While six biological pathways were found to be associated with cirrhosis, cell adhesion was the only pathway associated with cirrhosis after Bonferroni correction. In contrast to cirrhosis, DEFA-1 and ITGAM levels were inversely associated with HCC risk. Conclusions: Pending validation, these findings highlight the important role of immunological markers in predicting HCV-related cirrhosis even 11 years post-enrollment.

This study aims to examine the determinants of maternal healthcare choice for children under five years old with pneumonia in Vietnam. The choices include taking their children to the hospitals, staying at home and using self-medication, or choosing traditional method by consulting a traditionalist or a spiritualist. We use the multinomial logit model to study a collection of 215 observations from onsite surveys, including different groups of ethnic minorities. The results indicate that ethnicity, residence, education and income level determine the mothers’ care seeking behaviors for children with pneumonia. The findings are expected to provide better insights into the behavior of the ethnic minority mothers when dealing with pneumonia and help the Vietnamese authorities alleviate this recurring disease.

The application of Next Generation Sequencing (NGS) technologies in cancer research has accelerated the discovery of somatic mutations; however, it has not mirrored the same progress in the identification of cancer associated germline variation. With the goal to inform future studies on commonly used methods and their degree of success and limitations in identifying germline variants associated with cancer, we performed a review of the English literature for genome-wide germline sequencing studies aimed at identifying new cancer susceptibility genes or variants. A key words search in 2005-April 2017 PubMed yielded 7,349 articles which were checked against the following exclusion criteria: non-cancer (1852), somatic mutations (1764), methods (905), reviews (872), non-human (735), expression (272), targeted sequencing (224), commentaries (170), epigenetic (135), non-English (89), functional (85), clinical studies (51), others (44). The remaining 151 publications were examined in-depth and coded in an Access database according to ~60 fields, capturing information on: publication (journal, year, author, title, abstract), study design (goal; cancer type; population and ethnicity; discovery, technical validation, and replication phases; numbers and characteristics of cases, controls, families used in each phase), sequencing technique (center, technology, coverage, reads aligner, variants caller, QCs), data analysis (variants annotation, candidate genes, filtering strategy, association test), in silico and experimental functional assessment, and key conclusions (main results, challenges, next steps). The discovery phase of the examined papers was largely based on familial cases (77%), exome/genome sequencing of one single family (31%), and restricted to the analysis of candidate genes lists. The distribution of ethnicity for the sequenced cancer patients was 38% European, 11% Asian, 10% African, 5% multi-ethnic, 4% African American, 3% Latino/Hispanic, 3% Middle Eastern, 1% Jewish, and 25% unreported. Breast, prostate, colorectal, and lung cancer represented ~40% of the assessed articles, and the remaining 60% a diverse group of rare cancer types. Most studies (~80%) included a technical validation phase, but without clear success rate. Only 60% of studies included a replication phase in an independent population. Although most studies (~80%) described the identification of multiple germline variants and genes thought to have a role in cancer susceptibility, the supporting evidence was often disparate or not clearly stated. Our findings underscore the importance of establishing standards for reporting filtering strategies and rational for variant identification. We identified untapped potentials in the utilization of more/larger families, the harmonization of results across studies, and the expansion beyond candidate genes. Citation Format: Rolando Barajas, Elise Hoover, Mindy Clyne, Tram Lam, Leah Mechanic, Alisa Goldstein, Elizabeth Gillanders, Melissa Rotunno. A literature review of whole exome and genome sequencing population studies for identifying novel germline mutations in relation to cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1600.

To assess and advance training of twenty-first century cancer epidemiologists, the National Cancer Institute (NCI) sought to obtain a snapshot of the cancer epidemiology training landscape by conducting a survey across academic institutions and cancer centers, focusing on four key training areas driving current cancer epidemiology research (“drivers”): (1) collaboration, (2) novel methods/technologies, (3) multilevel analysis, and (4) knowledge integration. Complementary to the survey, we conducted a portfolio analysis of active NCI-funded training grants. In the present report, we provide our findings from this effort and contribute to the on-going conversation regarding the training of next-generation cancer epidemiologists. Analyses and insights gained from conversations with leaders/educators across 24 academic institutions/cancer centers and the portfolio analysis of training grants echoed contemporaneous conversation that cancer epidemiology training must adapt to meet the needs of the changing research environment. Currently, with the exception of novel methods/technologies, cancer epidemiology trainees receive the majority of their training in collaboration, multilevel approaches, and knowledge integration/translation either informally, ad hoc, or not at all; exposure to these identified drivers varied considerably by institution, mentor, and other external as well as internal factors.