Julia Butt1, Matthew G Varga2, William J Blot3, Lauren Teras4, Kala Visvanathan5, Loïc Le Marchand6, Christopher Haiman7, Yu Chen8, Ying Bao9, Howard D Sesso10, Sylvia Wassertheil-Smoller11, Gloria Y F Ho12, Lesley E Tinker13, Richard M Peek14, John D Potter15, Timothy L Cover16, Laura H Hendrix17, Li-Ching Huang18, Terry Hyslop19, Caroline Um4, Francine Grodstein20, Mingyang Song21, Anne Zeleniuch-Jacquotte8, Sonja Berndt22, Allan Hildesheim22, Tim Waterboer23, Michael Pawlita23, Meira Epplein24. 1. Infection and Cancer Epidemiology, Division of Molecular Diagnostics of Oncogenic Infections, German Cancer Research Center, Heidelberg, Germany; Cancer Control and Population Sciences Program, Duke Cancer Institute, and Department of Population Health Sciences, Duke University, Durham, North Carolina. 2. University of North Carolina at Chapel Hill, Department of Epidemiology, Gillings School for Global Public Health and Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina. 3. Division of Epidemiology, Vanderbilt University Medical Center, Nashville, Tennessee. 4. Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia. 5. Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland. 6. Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii. 7. University of Southern California and University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California. 8. Department of Population Health, New York University School of Medicine, New York, New York. 9. Brigham and Women's Hospital, Boston, Massachusetts. 10. Brigham and Women's Hospital, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 11. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York. 12. Department of Occupational Medicine, Epidemiology and Prevention, Feinstein Institute for Medical Research, Northwell Health; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York. 13. Cancer Prevention Program, Division of Public Health Sciences at Fred Hutchinson Cancer Research Center, Seattle, Washington. 14. Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. 15. Fred Hutchinson Cancer Research Center, Seattle, Washington. 16. Department of Medicine and Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee. 17. Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina. 18. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee. 19. Cancer Control and Population Sciences Program, Duke Cancer Institute, and Department of Population Health Sciences, Duke University, Durham, North Carolina; Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina. 20. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 21. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 22. Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland. 23. Infection and Cancer Epidemiology, Division of Molecular Diagnostics of Oncogenic Infections, German Cancer Research Center, Heidelberg, Germany. 24. Cancer Control and Population Sciences Program, Duke Cancer Institute, and Department of Population Health Sciences, Duke University, Durham, North Carolina. Electronic address: meira.epplein@duke.edu.
Abstract
BACKGROUND & AIMS: Previous studies reported an association of the bacteria Helicobacter pylori, the primary cause of gastric cancer, and risk of colorectal cancer (CRC). However, these findings have been inconsistent, appear to vary with population characteristics, and may be specific for virulence factor VacA. To more thoroughly evaluate the potential association of H pylori antibodies with CRC risk, we assembled a large consortium of cohorts representing diverse populations in the United States. METHODS: We used H pylori multiplex serologic assays to analyze serum samples from 4063 incident cases of CRC, collected before diagnosis, and 4063 matched individuals without CRC (controls) from 10 prospective cohorts for antibody responses to 13 H pylori proteins, including virulence factors VacA and CagA. The association of seropositivity to H pylori proteins, as well as protein-specific antibody level, with odds of CRC was determined by conditional logistic regression. RESULTS: Overall, 40% of controls and 41% of cases were H pylori-seropositive (odds ratio [OR], 1.09; 95% CI, 0.99-1.20). H pylori VacA-specific seropositivity was associated with an 11% increased odds of CRC (OR, 1.11; 95% CI, 1.01-1.22), and this association was particularly strong among African Americans (OR, 1.45; 95% CI, 1.08-1.95). Additionally, odds of CRC increased with level of VacA antibody in the overall cohort (P = .008) and specifically among African Americans (P = .007). CONCLUSIONS: In an analysis of a large consortium of cohorts representing diverse populations, we found serologic responses to H pylori VacA to associate with increased risk of CRC risk, particularly for African Americans. Future studies should seek to understand whether this marker is related to virulent H pylori strains carried in these populations.
BACKGROUND & AIMS: Previous studies reported an association of the bacteria Helicobacter pylori, the primary cause of gastric cancer, and risk of colorectal cancer (CRC). However, these findings have been inconsistent, appear to vary with population characteristics, and may be specific for virulence factor VacA. To more thoroughly evaluate the potential association of H pylori antibodies with CRC risk, we assembled a large consortium of cohorts representing diverse populations in the United States. METHODS: We used H pylori multiplex serologic assays to analyze serum samples from 4063 incident cases of CRC, collected before diagnosis, and 4063 matched individuals without CRC (controls) from 10 prospective cohorts for antibody responses to 13 H pylori proteins, including virulence factors VacA and CagA. The association of seropositivity to H pylori proteins, as well as protein-specific antibody level, with odds of CRC was determined by conditional logistic regression. RESULTS: Overall, 40% of controls and 41% of cases were H pylori-seropositive (odds ratio [OR], 1.09; 95% CI, 0.99-1.20). H pylori VacA-specific seropositivity was associated with an 11% increased odds of CRC (OR, 1.11; 95% CI, 1.01-1.22), and this association was particularly strong among African Americans (OR, 1.45; 95% CI, 1.08-1.95). Additionally, odds of CRC increased with level of VacA antibody in the overall cohort (P = .008) and specifically among African Americans (P = .007). CONCLUSIONS: In an analysis of a large consortium of cohorts representing diverse populations, we found serologic responses to H pylori VacA to associate with increased risk of CRC risk, particularly for African Americans. Future studies should seek to understand whether this marker is related to virulent H pylori strains carried in these populations.
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