Inflammation has been hypothesized to be involved in the etiology of multiple cancers, and emerging evidence has implicated an important role of chronic inflammation, due to both biologic agents and other causes, suggesting that cancer is a situation of unhealed infection. This Career Development Award will provide Dr. Epplein, a tenure-track Assistant Professor of Epidemiology at Vanderbilt University, with the training needed to further her career in the research of infection and inflammation as they relate to cancer risk. While Dr. Epplein has had excellent training in epidemiological methodology, statistical analysis, and scientific writing during her doctoral and post-doctoral experiences, she requires further training to gain expertise in her chosen research area of inflammation and cancer. The specific project proposed in this award, focusing on Helicobacter pylori, host inflammatory cytokines, and gastric cancer risk, will serve as a training opportunity so that Dr. Epplein can expand her expertise and become a leader in the study of infection, inflammation, and cancer. For this training project, she could not be better served than by the experts in molecular epidemiology (Wei Zheng), gastric cancer (Pelayo Correa), and H. pylori biology (Richard Peek) at Vanderbilt University. Her research plan seeks to further our understanding of the etiology of gastric cancer, the second most common cause of death from cancer worldwide, through analyses of host and bacterial factors in a high-risk population. H. pylori, a gram-negative spiral bacterium that resides in the stomach of approximately half of the world's population and is generally acquired in childhood, is currently the strongest known risk factor for gastric cancer.1-4 And, while the proteins CagA and VacA that are found in some strains of H. pylori have been consistently identified as virulence factors, very recent new research exploring the diversity of H. pylori has revealed 15 distinct H. pylori proteins. At the same time, a strong association has been seen between host inflammatory profile and gastric cancer risk, suggesting that it is the combination of H. pylori strain-specific infection and host inflammatory response that creates the fertile ground for which gastric cancer to grow. To study these complex relationships, Dr. Epplein will conduct a nested case-control study within the Shanghai Health Studies to investigate the association of gastric cancer risk with: 1) H. pylori strain-specific infections;2) host systemic inflammatory cytokines;and 3) the potential interactions between H. pylori infection and host inflammatory cytokines. Ultimately this research aims to aid in more appropriately assessing overall risk to identify high-risk subjects for primary and secondary prevention of gastric cancer. With the knowledge and experience provided by this CDA, Dr. Epplein will be prepared to secure the funding necessary to establish a multidisciplinary research program on gastric cancer etiology, expanding her research on this subject to other high-risk populations such as low-income African Americans. Furthermore, it will give her the basis to establish an independent long-term career focusing more broadly on infection, inflammation, and cancer.

Public Health Relevance

Inflammation has been hypothesized to be involved in the etiology of multiple cancers, including those of the liver (HBV, HCV), cervix (HPV), and stomach (Helicobacter pylori), and it has even been postulated that cancer is a situation of unhealed infection. The aim of the research plan proposed in this award is to be able to identify the most virulent H. pylori strains and the most vulnerable populations to gastric cancer, the second leading cause of death from cancer worldwide, so that we can more appropriately assess risk and focus diagnostic testing and eradication therapy to prevent the development of gastric cancer. This investigation into the bacteria-host-environment risk factors related to gastric cancer will both further the field of gastric cancer etiology and provide a strong training opportunity for a future career in the broader field of inflammation and cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Academic/Teacher Award (ATA) (K07)
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Study Section
Subcommittee G - Education (NCI)
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Perkins, Susan N
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Vanderbilt University Medical Center
Internal Medicine/Medicine
Schools of Medicine
United States
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Epplein, Meira; Butt, Julia; Zhang, Yang et al. (2018) Validation of a Blood Biomarker for Identification of Individuals at High Risk for Gastric Cancer. Cancer Epidemiol Biomarkers Prev 27:1472-1479
Cai, Hui; Ye, Fei; Michel, Angelika et al. (2016) Helicobacter pylori blood biomarker for gastric cancer risk in East Asia. Int J Epidemiol 45:774-81
Epplein, Meira; Peek Jr, Richard M; Blot, William J (2014) Helicobacter pylori Biomarkers and Risk of Colorectal Oncogenesis--Response. Cancer Epidemiol Biomarkers Prev 23:366
Epplein, Meira; Zheng, Wei; Li, Honglan et al. (2014) Diet, Helicobacter pylori strain-specific infection, and gastric cancer risk among Chinese men. Nutr Cancer 66:550-7
Epplein, Meira; Bostick, Roberd M; Mu, Lina et al. (2014) Challenges and opportunities in international molecular cancer prevention research: An ASPO Molecular Epidemiology and the Environment and International Cancer Prevention Interest Groups Report. Cancer Epidemiol Biomarkers Prev 23:2613-7
Epplein, Meira; Burk, Raymond F; Cai, Qiuyin et al. (2014) A prospective study of plasma Selenoprotein P and lung cancer risk among low-income adults. Cancer Epidemiol Biomarkers Prev 23:1238-44
Epplein, Meira; Pawlita, Michael; Michel, Angelika et al. (2013) Helicobacter pylori protein-specific antibodies and risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 22:1964-74
Epplein, Meira; Xiang, Yong-Bing; Cai, Qiuyin et al. (2013) Circulating cytokines and gastric cancer risk. Cancer Causes Control 24:2245-50
Kweon, Sun-Seog; Shu, Xiao-Ou; Xiang, Yongbing et al. (2013) Intake of specific nonfermented soy foods may be inversely associated with risk of distal gastric cancer in a Chinese population. J Nutr 143:1736-42
Epplein, Meira; Zheng, Wei; Xiang, Yong-Bing et al. (2012) Prospective study of Helicobacter pylori biomarkers for gastric cancer risk among Chinese men. Cancer Epidemiol Biomarkers Prev 21:2185-92