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Article

Association of Combined Sero-Positivity to Helicobacter pylori and Streptococcus gallolyticus with Risk of Colorectal Cancer

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Cancer Control and Population Health Sciences Program, Duke Cancer Institute and Department of Population Health Sciences, Duke University, Durham, NC 27705, USA
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Epidemiology Program, University of Hawai’i Cancer Center, Honolulu, HI 96813, USA
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Department of Medicine and Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
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Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212, USA
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Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA
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Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA
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Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, USA
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Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN 37203, USA
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Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
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Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA 30303, USA
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Department of Epidemiology, Johns Hopkins School of Public Health, and Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
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Department of Population Health, New York University Grossman School of Medicine, New York, NY 10016, USA
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Brigham and Women’s Hospital, Boston, MA 02215, USA
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Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA
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Centre for Public Health Research, Massey University, Wellington 6140, New Zealand
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Department of Mathematics, Duke University, Durham, NC 27705, USA
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Center for Genetic Epidemiology, Department of Preventive Medicine, University of Southern California and USC Norris Comprehensive Cancer Center, Los Angeles, CA 90089, USA
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Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA
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Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
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Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Microorganisms 2020, 8(11), 1698; https://doi.org/10.3390/microorganisms8111698
Received: 2 October 2020 / Revised: 19 October 2020 / Accepted: 29 October 2020 / Published: 30 October 2020
(This article belongs to the Section Gut Microbiota)
Previously, we found that risk of colorectal cancer (CRC) is increased in individuals with serum antibody response to both Helicobacter pylori (HP) Vacuolating Cytotoxin (VacA) toxin or Streptococcus gallolyticus (SGG) pilus protein Gallo2178. In the present analysis, we tested the hypothesis that combined seropositivity to both antigens is a better indicator of CRC risk than seropositivity to single antigens. We used multiplex serologic assays to analyze pre-diagnostic serum for antibody responses from 4063 incident CRC cases and 4063 matched controls from 10 US cohorts. To examine whether combined SGG Gallo2178 and HP VacA sero-status was associated with CRC risk, we used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Compared to dual sero-negative individuals, there was no increased risk for individuals sero-positive to SGG Gallo2178 only (OR: 0.93; 95% CI: 0.66–1.31) or to HP VacA only (OR: 1.08; 95% CI: 0.98–1.19). However, dual sero-positive individuals had a >50% increased odds of developing CRC (OR: 1.54; 95% CI: 1.16–2.04), suggesting an interaction between antibody responses to these two pathogens and CRC risk (pinteraction = 0.06). In conclusion, this study suggests that dual sero-positivity to HP VacA and SGG Gallo2178 is an indicator of increased risk of CRC. View Full-Text
Keywords: Helicobacter pylori; Streptococcus gallolyticus; colorectal cancer; sero-positivity; antibodies Helicobacter pylori; Streptococcus gallolyticus; colorectal cancer; sero-positivity; antibodies
MDPI and ACS Style

Epplein, M.; Le Marchand, L.; Cover, T.L.; Song, M.; Blot, W.J.; Peek, R.M.; Teras, L.R.; Visvanathan, K.; Chen, Y.; Sesso, H.D.; Zeleniuch-Jacquotte, A.; Berndt, S.I.; Potter, J.D.; Ryser, M.D.; Haiman, C.A.; Wassertheil-Smoller, S.; Tinker, L.F.; Waterboer, T.; Butt, J. Association of Combined Sero-Positivity to Helicobacter pylori and Streptococcus gallolyticus with Risk of Colorectal Cancer. Microorganisms 2020, 8, 1698. https://doi.org/10.3390/microorganisms8111698

AMA Style

Epplein M, Le Marchand L, Cover TL, Song M, Blot WJ, Peek RM, Teras LR, Visvanathan K, Chen Y, Sesso HD, Zeleniuch-Jacquotte A, Berndt SI, Potter JD, Ryser MD, Haiman CA, Wassertheil-Smoller S, Tinker LF, Waterboer T, Butt J. Association of Combined Sero-Positivity to Helicobacter pylori and Streptococcus gallolyticus with Risk of Colorectal Cancer. Microorganisms. 2020; 8(11):1698. https://doi.org/10.3390/microorganisms8111698

Chicago/Turabian Style

Epplein, Meira, Loïc Le Marchand, Timothy L. Cover, Mingyang Song, William J. Blot, Richard M. Peek, Lauren R. Teras, Kala Visvanathan, Yu Chen, Howard D. Sesso, Anne Zeleniuch-Jacquotte, Sonja I. Berndt, John D. Potter, Marc D. Ryser, Christopher A. Haiman, Sylvia Wassertheil-Smoller, Lesley F. Tinker, Tim Waterboer, and Julia Butt. 2020. "Association of Combined Sero-Positivity to Helicobacter pylori and Streptococcus gallolyticus with Risk of Colorectal Cancer" Microorganisms 8, no. 11: 1698. https://doi.org/10.3390/microorganisms8111698

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