Immunoepidemiology in Carcinogenesis
(Korea) 2021-07-14 10:00
, (Republic of Korea) 2021-07-14 10:00
- National Cancer Institute, NIH
Immunoepidemiology can be defined as the study of the diversity and distribution of immune responses in populations as well as understanding the determinants of immune responses. Our knowledge of immunology has evolved rapidly in recent years, but understanding the heterogeneity in immunologic responses and the role of immunity in cancer etiology at the population level is still unknown.
Epidemiology can employ various study designs to answer a research question from various angles. Gastric cancer occurs through a cascade of events initiated by Helicobacter pylori infection in the gastric mucosa, followed by chronic gastritis, atrophic gastritis, intestinal metaplasia, dysplasia, and finally cancer. In the investigation of how inflammation plays role in gastric carcinogenesis, we have used case-case, case-control, and case-cohort designs in comparing groups of individuals in different steps to carcinogenesis. To comprehensively assess the inflammatory pathways, we measured circulating inflammation-related markers using various multiplex technologies. However, we found weak associations between these markers and gastric cancer that have limited utility in the clinical setting for both early detection or prediction.
Another aspect of inflammation-gastric cancer is on the bacterial side. We used novel immunoproteomic technology to measure antibodies against H. pylori and Epstein-Barr virus (EBV) to explore differences of these markers in those with or without gastric cancer and EBV-positive and -negative tumors, respectively. In our first comprehensive assessment of anti-H. pylori humoral profiles in gastric cancer, we found decreased responses to multiple proteins in gastric cancer. The EBV-associated gastric cancer-specific humoral response was exclusively directed against lytic cycle immediate-early and early antigens, unlike other EBV-associated malignancies that are primarily restricted to late lytic antigens.
A well-conducted descriptive analysis can answer the proposed question(s) and lead to novel questions or hypotheses. From the observation of an unexpected increase in gastric cancer in certain groups of Western populations, we hypothesized that this new trend is due to a risk factor other than H. pylori infection, which has been decreasing in the population. Autoimmune gastritis is an alternative pathway that has been understudied and using a prospective cohort study, we found that gastric autoantibodies can predict later gastric cancer risk.
Immunoepidemiology is in its infancy. Synthesis of epidemiologic methodologies with knowledge and technologies in immunology will greatly advance our understanding of the role of immunity in populations.
[Education & Employment]
1997-2004 Seoul National University College of Medicine (SNUCM), Korea M.D
2008-2011 Department of Preventive Medicine, SNUCM, Korea Resident
2008-2010 Department of Preventive Medicine, SNUCM, Korea M.S.
2011-2014 Department of Preventive Medicine, SNUCM, Korea Basic Research Fellow
2011-2015 Department of Preventive Medicine, SNUCM, Korea Ph.D.
2015-2016 Department of Preventive Medicine, SNUCM, Korea Postdoctoral Fellow
2016-2020 Division of Cancer Epidemiology and Genetics, National Cancer Institute, US Postdoctoral Fellow
2020-Present Division of Cancer Epidemiology and Genetics, National Cancer Institute, US Research Fellow
[Selected publications in recent 5 years]
• Song M, Rabkin CS, Ito H, Oze I, Koyanagi YN, Pfeiffer RM, Kasugai Y, Matsuo K, Camargo MC. Circulating Immune- and Inflammation-related Biomarkers and Early-stage Noncardia Gastric Cancer. Eur J Cancer Prev. Accepted.
• Camargo MC, Song M, Ito H, Oze I, Rabkin CS, Matsuo K. Associations of Circulating Mediators of Inflammation, Cell Regulation and Immune Response with Esophageal Squamous Cell Carcinoma. J Cancer Res Clin Oncol. 2021 Jun 14. doi: 10.1007/s00432-021-03687-3.
• Camargo MC, Song M, Sawada N, Inoue M, Shimazu T, Charvat H, Pfeiffer RM, Yamaji T, Tsugane S, Rabkin CS.
Prediagnostic Circulating Inflammation-related Biomarkers and Gastric Cancer: A Case-Cohort Study in Japan. Cytokine. 2021 Aug;144:155558. doi: 10.1016/j.cyto.2021.155558.
• Song L*, Song M*, Camargo MC, Van Duine J, Williams S, Chung Y, Kim KM, Lissowska J, Sivins A, Kim S, Gao W, Karthikeyan K, Park J, Leja M, Cohen JI, LaBaer J, Qiu J, Rabkin CS. Identification of Anti-Epstein-Barr Virus (EBV) Antibody Signature in EBV-Associated Gastric Carcinoma. Gastric Cancer. 2021 Mar 4. doi: 10.1007/s10120-021-01170-z.
• Song L*, Song M*, Rabkin CS, Williams S, Chung Y, Van Duine J, Liao LM, Karthikeyan K, Gao W, Park JG, Tang Y, Lissowska Jl, Qiu J, LaBaer J, Camargo MC. Helicobacter pylori Immunoproteomic Profiles in Gastric Cancer. J Proteome Res. 2020 Oct 27. doi: 10.1021/acs.jproteome.0c00466.
• Van Alsten SC, Rabkin CS, Sawada N, Shimazu T, Charvat H, Yamaji T, Inoue M, Kemp TJ, Pinto LA, Camargo MC, Tsugane S, Song M. Metabolic Syndrome, Physical Activity and Inflammation: A Cross-Sectional Analysis of 110 Circulating Biomarkers in Japanese Adults. Cancer Epidemiol Biomarkers Prev. 2020 Aug;29(8):1639-1646. doi: 10.1158/1055-9965.EPI-19-1513.
• Song M, Latorre G, Ivanovic D, Camargo CM, Rabkin CS. Autoimmune Diseases and Gastric Cancer Risk: A Meta-Analysis. Cancer Res Treat. 2019 Jul;51(3):841-850. doi: 10.4143/crt.2019.151.
• Song M, Sasazuki S, Camargo MC, Shimazu T, Charvat H, Yamaji T, Sawada N, Kemp TJ, Pfeiffer RM, Hildesheim A, Pinto LA, Rabkin CS, Tsugane S. Circulating Inflammatory Markers and Colorectal Cancer Risk: A Prospective Case-cohort Study in Japan. Int J Cancer. 2018 Dec 1;143(11):2767-2776. doi: 10.1002/ijc.31821.
• Song M, Rabkin CS, Torres J, Kemp TJ, Zabaleta J, Pinto LA, Hildesheim A, Sánchez-Figueroa L, Guarner J, Herrera-Goepfert R, Parsonnet J, Camargo MC. Circulating Inflammation-related Markers and Advanced Gastric Premalignant Lesions. J Gastroenterol Hepatol. 2018 Oct 24. doi: 10.1111/jgh.14518.
• Chen Y, Wu F, Saito E, Ling Y, Song M, Luu HN, Gupta PC, Tamakoshi A, Shu XO, Koh WP, Xiang YB, Park SK, Matsuo K, Nagata C, Sagawara Y, Qiao YL, You SL, Wang R, Shin MH, Pan WH, Pednkar MS, Tsugane S, Cai H, Yuan JM, Gao YT, Tsuji I, Kanemura S, Ito H, Wada K, Ahn YO, Yoo KY, Ahsan H, Chia KS, Boffetta P, Zheng W, Inoue M, Kang D, Potter JD. Association between type 2 diabetes and risk of death from cancer: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium. Diabetologia. 2017 Jun;60(6):1022-1032. doi: 10.1007/s00125-017-4229-z.