Meira Epplein

Overview:

Meira Epplein is a cancer epidemiologist interested in modifiable risk factors in under-served populations, with a focus on the association of infection and cancer.  She became Co-Leader of Cancer Control and Population Sciences at Duke Cancer Institute and Associate Professor of Population Health Sciences in the Duke University Medical Center in May of 2017.  Previously, she was a tenured faculty member at Vanderbilt University Medical Center, after two years as a post-doctoral fellow with the Multiethnic Cohort Study at the University of Hawaii.  Prior to earning her PhD in epidemiology from the University of Washington, she completed an MA in international studies, and spent five years as a program officer for the Asian research think tank, the National Bureau of Asian Research.

Dr. Epplein’s research program has centered around the bacteria Helicobacter pylori, a spiral, gram-negative bacterium that infects approximately 50% of the world’s population, and is the leading carcinogenic infectious agent according to the International Agency for Research on Cancer.  Her research seeks to understand the heterogeneity of H. pylori, to determine the most toxigenic forms of the bacteria so to identify the highest risk populations which can then be targeted for antibiotic therapy, which has been shown to be effective for risk reduction. At the same time, she is committed to furthering our understanding of the co-factors involved in both H. pylori-associated disease risk and benefit, as the bacteria has inhabited the stomachs of humans for over 100,000 years, and so very likely also confers certain biological advantages to its hosts.

As Principal Investigator, she has obtained three large NIH-funded grants to further explore the epidemiology of H. pylori heterogeneity: a 5-year career development award (K07) from NCI that focuses on infection, inflammation, and cancer; a 5-year R01 from NCI to develop an H. pylori blood biomarker for gastric cancer risk in East Asia; and a 4-year R01, again funded by NCI, to further investigate, in a large consortium of prospective cohorts across the United States, the novel preliminary finding of H. pylori protein-specific antibodies and the risk of colorectal cancer. She also serves as a Co-Investigator and lead gastric cancer and H. pylori researcher for the Southern Community Cohort Study (SCCS). In addition to serving as a standing member of the study section NCI Subcommittee J (Career Development Awards), she is an editorial board member of the journal Cancer Epidemiology, Biomarkers & Prevention, and is co-chair of the 2017 American Society of Preventive Oncology Annual Meeting Program Committee. 

Area of expertise: Epidemiology

Positions:

Associate Professor in Population Health Sciences

Population Health Sciences
School of Medicine

Associate Professor in Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.A. 1997

University of Washington

M.S. 2005

University of Washington

Ph.D. 2007

University of Washington

Grants:

Helicobacter pylori protein-specific antibodies and colorectal cancer risk

Administered By
Duke Cancer Institute
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

An Approach to the Primary and Secondary Prevention of Gastric Cancer in the United States.

BACKGROUND & AIMS: Gastric cancer (GC) remains a leading cause of mortality among certain racial, ethnic, and immigrant groups in the United States (US). The majority of GCs are diagnosed at advanced stages, and overall survival remains poor. There exist no structured national strategies for GC prevention in the US. METHODS: On March 5-6, 2020 a summit of researchers, policy makers, public funders, and advocacy leaders was convened at Stanford University to address this critical healthcare disparity. After this summit, a writing group was formed to critically evaluate the effectiveness, potential benefits, and potential harms of methods of primary and secondary prevention through structured literature review. This article represents a consensus statement prepared by the writing group. RESULTS: The burden of GC is highly inequitably distributed in the US and disproportionately falls on Asian, African American, Hispanic, and American Indian/Alaskan Native populations. In randomized controlled trials, strategies of Helicobacter pylori testing and treatment have been demonstrated to reduce GC-specific mortality. In well-conducted observational and ecologic studies, strategies of endoscopic screening have been associated with reduced GC-specific mortality. Notably however, all randomized controlled trial data (for primary prevention) and the majority of observational data (for secondary prevention) are derived from non-US sources. CONCLUSIONS: There exist substantial, high-quality data supporting GC prevention derived from international studies. There is an urgent need for cancer prevention trials focused on high-risk immigrant and minority populations in the US. The authors offer recommendations on how strategies of primary and secondary prevention can be applied to the heterogeneous US population.
Authors
Huang, RJ; Epplein, M; Hamashima, C; Choi, IJ; Lee, E; Deapen, D; Woo, Y; Tran, T; Shah, SC; Inadomi, JM; Greenwald, DA; Hwang, JH
MLA Citation
Huang, Robert J., et al. “An Approach to the Primary and Secondary Prevention of Gastric Cancer in the United States.Clin Gastroenterol Hepatol, Oct. 2021. Pubmed, doi:10.1016/j.cgh.2021.09.039.
URI
https://scholars.duke.edu/individual/pub1498553
PMID
34624563
Source
pubmed
Published In
Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association
Published Date
DOI
10.1016/j.cgh.2021.09.039

Risk factors for gastric cancers in the United States: Variation by anatomic site and race/ethnicity.

<jats:p> 189 </jats:p><jats:p> Background: Gastric cancer (GC) is a high mortality cancer in the US. Differences in risk factors by anatomic location and race/ethnicity have been suggested but remain understudied in the US population. Methods: The Multiethnic Cohort (MEC) is a prospective cohort study that collected data on 5 racial/ethnic groups [Whites (W), Blacks (B), Latino (L), Japanese-American (JA), and Hawaiian (HA)] from Hawaii and Los Angeles in 1993-1996. Participants completed a detailed baseline survey and were followed for development of incident cancer. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) to identify GC risk factors by anatomic location (cardia, non-cardia) and by race/ethnicity. Results: Data from 192,626 participants was available. The cohort was 25% W, 17% B, 23% L, 28% JA, and 7% HA. During a median follow up of 20.3 years, 1,109 non-cardia and 201 cardia incident GCs were diagnosed. Older age (per year, non-cardia HR 1.08, 95% CI 1.07-1.92; cardia HR 1.06, 95% CI 1.05-1.09), male sex (non-cardia HR 1.6, 95% CI 1.4-1.8; cardia HR 3.0, 95% CI 2.1-4.4), and current (non-cardia HR 1.7, 95% CI 1.5-2.2, cardia HR 3.4, 95% CI 2.2-5.3) or former (non-cardia HR 1.3, 95% CI 1.1-1.5; cardia HR 2.0, 95% CI 1.3-2.9) smoking were associated with both cancer types. Notably, race/ethnicity (ref W: B HR 3.0, 95% CI 2.2-4.0; L HR 2.5, 95% CI 1.8-3.3; JA HR 3.9, 95% CI 3.0-5.1; HA HR 3.9, 95% CI 2.8-5.5), foreign-born (ref: self &amp; parents US born: HR 1.3 95% CI 1.1-1.7), and family history of GC (OR 1.9, 95% CI 1.5-2.3) were associated with non-cardia GC. BMI ≥30 (HR 1.6, 95% CI 1.1-2.3), having ≥1 drink/week (HR 1.6, 95% CI 1.1-2.3), and being JA (ref W: HR 1.9, 95% CI 1.2-2.9) were associated with cardia GC. Risk factors other than age differed by race/ethnicity for non-cardia GC. Male sex was a risk factor for B, L and JA only. Having less than a high school education was a risk factor for B and JA only, smoking a risk factor for L and JA only, and having diabetes a risk factor for B only. Being in the highest sodium intake quartile was a risk factor among W and HA. A family history of GC was a risk factor for W, L, and JA. Having foreign-born parents was a risk factor for W and being foreign-born was a risk factor for JA. Conclusions: GC risk factors differ between subtypes and, for non-cardia, between race/ethnic groups. These differences provide an insight into the etiology of GC and the disproportionate incidence rates in high-risk groups, potentially aiding in the design of targeted intervention strategies. </jats:p>
Authors
In, H; Friedmann, P; Sarkar, S; Rapkin, B; Castle, PE; Epplein, M
MLA Citation
In, Haejin, et al. “Risk factors for gastric cancers in the United States: Variation by anatomic site and race/ethnicity.Journal of Clinical Oncology, vol. 39, no. 3_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 189–189. Crossref, doi:10.1200/jco.2021.39.3_suppl.189.
URI
https://scholars.duke.edu/individual/pub1480814
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
189
End Page
189
DOI
10.1200/jco.2021.39.3_suppl.189

Prediagnostic Antibody Responses to Fusobacterium nucleatum Proteins Are Not Associated with Risk of Colorectal Cancer in a Large U.S. Consortium.

BACKGROUND: The association between prediagnostic antibody responses to Fusobacterium nucleatum (F. nucleatum) and subsequent risk of colorectal cancer is not established. METHODS: We conducted a nested case-control study of 8,126 participants in a consortium of 10 prospective cohorts in the United States. RESULTS: Higher seroprevalence of any F. nucleatum antibody was observed among non-White participants (51.1%) compared with White participants (31.2%). We did not find any statistically significant association between seropositivity to any of the eight F. nucleatum proteins and colorectal cancer risk. CONCLUSIONS: Prediagnostic antibody responses to F. nucleatum proteins were not associated with the risk of colorectal cancer. IMPACT: Future studies may consider a more specific detection of the immunoglobulin isotypes or focus on examining F. nucleatum in stool or tissue samples.
Authors
Lo, C-H; Blot, WJ; Teras, LR; Visvanathan, K; Le Marchand, L; Haiman, CA; Chen, Y; Sesso, HD; Wassertheil-Smoller, S; Tinker, LF; Peek, RM; Potter, JD; Cover, TL; Zeleniuch-Jacquotte, A; Berndt, SI; Waterboer, T; Epplein, M; Butt, J; Song, M
MLA Citation
Lo, Chun-Han, et al. “Prediagnostic Antibody Responses to Fusobacterium nucleatum Proteins Are Not Associated with Risk of Colorectal Cancer in a Large U.S. Consortium.Cancer Epidemiol Biomarkers Prev, vol. 30, no. 6, June 2021, pp. 1279–82. Pubmed, doi:10.1158/1055-9965.EPI-20-1471.
URI
https://scholars.duke.edu/individual/pub1476813
PMID
33737297
Source
pubmed
Published In
Cancer Epidemiol Biomarkers Prev
Volume
30
Published Date
Start Page
1279
End Page
1282
DOI
10.1158/1055-9965.EPI-20-1471

Immunostimulatory membrane proteins potentiate H. pylori-induced carcinogenesis by enabling CagA translocation.

Infection with Helicobacter pylori is the single greatest risk factor for developing gastric adenocarcinoma. In prospective, population-based studies, seropositivity to the uncharacterized H. pylori proteins Hp0305 and Hp1564 was significantly associated with cancer risk in East Asia. However, the mechanism underlying this observation has not been elucidated. Here, we show that Hp0305 and Hp1564 act in concert with previously ascribed H. pylori virulence mechanisms to orchestrate cellular alterations that promote gastric carcinogenesis. In samples from 546 patients exhibiting premalignant gastric lesions, seropositivity to Hp0305 and Hp1564 was significantly associated with increased gastric atrophy across all stomach conditions. In vitro, depletion of Hp0305 and Hp1564 significantly reduced levels of gastric cell-associated bacteria and markedly impaired the ability of H. pylori to stimulate pro-inflammatory cytokine production. Remarkably, our studies revealed that Hp1564 is required for translocation of the oncoprotein CagA into gastric epithelial cells. Our data provide experimental insight into the molecular mechanisms governing novel H. pylori pathogenicity factors that are strongly associated with gastric disease and highlight the potential of Hp0305 and Hp1564 as robust molecular tools that can improve identification of individuals that are highly susceptible to gastric cancer. We demonstrate that Hp0305 and Hp1564 augment H. pylori-mediated inflammation and gastric cancer risk by promoting key bacteria-gastric cell interactions that facilitate delivery of oncogenic microbial cargo to target cells. Thus, therapeutically targeting microbial interactions driven by Hp0305/Hp1564 may enable focused H. pylori eradication strategies to prevent development of gastric malignancies in high-risk populations.
Authors
Varga, MG; Wood, CR; Butt, J; Ryan, ME; You, W-C; Pan, K; Waterboer, T; Epplein, M; Shaffer, CL
MLA Citation
Varga, Matthew G., et al. “Immunostimulatory membrane proteins potentiate H. pylori-induced carcinogenesis by enabling CagA translocation.Gut Microbes, vol. 13, no. 1, Jan. 2021, pp. 1–13. Pubmed, doi:10.1080/19490976.2020.1862613.
URI
https://scholars.duke.edu/individual/pub1471201
PMID
33382363
Source
pubmed
Published In
Gut Microbes
Volume
13
Published Date
Start Page
1
End Page
13
DOI
10.1080/19490976.2020.1862613

Auto-antibodies to p53 and the Subsequent Development of Colorectal Cancer in a U.S. Prospective Cohort Consortium.

BACKGROUND: Auto-antibodies to tumor suppressor p53 are found in a subset of patients with colorectal cancer. A recent prospective study in the United States has reported a significant 1.8-fold increased odds for colorectal cancer development with prediagnostic seropositivity to p53. In this study, we sought to examine this association in a U.S. colorectal cancer cohort consortium to evaluate the potential utility of p53 auto-antibodies as an early biomarker for colorectal cancer. METHODS: Auto-antibodies to p53 were measured in prediagnostic blood samples of 3,702 incident colorectal cancer cases and 3,702 controls, matched by age, race, and sex, from 9 U.S. prospective cohorts. The association of seropositivity to p53 with colorectal cancer risk, overall and by time between blood draw and diagnosis, was determined by conditional logistic regression. RESULTS: Overall, 5% of controls and 7% of cases were seropositive to p53, resulting in a statistically significant 33% increased colorectal cancer risk [odds ratio (OR), 1.33; 95% confidence interval (CI), 1.09-1.61]. By follow-up time, the association was only significant with colorectal cancer diagnoses within 4 years after blood draw (OR, 2.27; 95% CI, 1.62-3.19), but not thereafter (OR, 0.97; 95% CI, 0.76-1.24). CONCLUSIONS: In this large consortium of prospective cohorts, we found that prediagnostic seropositivity to tumor suppressor p53 was significantly associated with an over 2-fold increased odds of developing colorectal cancer within 4 years after blood draw. IMPACT: Our finding suggests that p53 seropositivity may not be a useful predictor of long-term colorectal cancer risk; however, it might be considered as a marker to aid in the early diagnosis of colorectal cancer.
Authors
Butt, J; Blot, WJ; Visvanathan, K; Le Marchand, L; Wilkens, LR; Chen, Y; Sesso, HD; Teras, L; Ryser, MD; Hyslop, T; Wassertheil-Smoller, S; Tinker, LF; Potter, JD; Song, M; Berndt, SI; Waterboer, T; Pawlita, M; Epplein, M
MLA Citation
Butt, Julia, et al. “Auto-antibodies to p53 and the Subsequent Development of Colorectal Cancer in a U.S. Prospective Cohort Consortium.Cancer Epidemiol Biomarkers Prev, vol. 29, no. 12, Dec. 2020, pp. 2729–34. Pubmed, doi:10.1158/1055-9965.EPI-20-0780.
URI
https://scholars.duke.edu/individual/pub1460794
PMID
32972968
Source
pubmed
Published In
Cancer Epidemiol Biomarkers Prev
Volume
29
Published Date
Start Page
2729
End Page
2734
DOI
10.1158/1055-9965.EPI-20-0780