TY - JOUR
T1 - Serologic Response to Helicobacter pylori Proteins Associated With Risk of Colorectal Cancer Among Diverse Populations in the United States
AU - Butt, Julia
AU - Varga, Matthew G.
AU - Blot, William J.
AU - Teras, Lauren
AU - Visvanathan, Kala
AU - Le Marchand, Loïc
AU - Haiman, Christopher
AU - Chen, Yu
AU - Bao, Ying
AU - Sesso, Howard D.
AU - Wassertheil-Smoller, Sylvia
AU - Ho, Gloria Y.F.
AU - Tinker, Lesley E.
AU - Peek, Richard M.
AU - Potter, John D.
AU - Cover, Timothy L.
AU - Hendrix, Laura H.
AU - Huang, Li Ching
AU - Hyslop, Terry
AU - Um, Caroline
AU - Grodstein, Francine
AU - Song, Mingyang
AU - Zeleniuch-Jacquotte, Anne
AU - Berndt, Sonja
AU - Hildesheim, Allan
AU - Waterboer, Tim
AU - Pawlita, Michael
AU - Epplein, Meira
N1 - Funding Information:
The Campaign Against Cancer and Stroke thanks the participants and staff for their contributions, as well as the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Department of Health and Mental Hygiene. The authors would like to thank the participants and staff of the Nurses’ Health Study and the Health Professionals Follow-up Study for their valuable contributions, as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. The authors assume full responsibility for analyses and interpretation of these data. The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II cohort. The authors express sincere appreciation to all Cancer Prevention Study-II participants, and to each member of the study and biospecimen management group. The authors would like to acknowledge the contribution from central cancer registries supported through the Centers for Disease Control and Prevention's National Program of Cancer Registries and cancer registries supported by the National Cancer Institute's Surveillance Epidemiology and End Results Program.
Funding Information:
Funding The National Cancer Institute funds: this consortium (R01 CA190428, principal investigator [PI]: Epplein); the Southern Community Cohort Study (U01 CA202979, PI: Blot); the New York University Women's Health Study (UM1 CA182934, Principal Investigator [PI]: Zeleniuch-Jaquotte; P30 CA016087, PI: Neel); the Nurses’ Health Study/Health Professionals Follow-Up Study (U01 CA167552; P01 CA087969; UM1 CA186107; UM1 CA167552); the Physicians’ Health Study (R01 CA097193; R01 CA040360; R01 HL034595); and the Multiethnic Cohort Study (U01 CA164973, PI: Le Marchand). R.M. Peek is supported by R01 DK058587 and R01 CA077955. T.L. Cover is supported by National Institutes of Health (NIH) R01 AI039657, R01 AI118932, P01 CA116087 and the Department of Veterans Affairs BX000627. M. Song is supported by the American Cancer Society (grant number MRSG-17-220-01–NEC); the 2017 American Association for Cancer Research-AstraZeneca Fellowship in Immuno-oncology Research (grant number 17-40-12-SONG to M.S.); the NIH (K99 CA215314 to M.S.). Matthew G. Varga is supported by NIH T32 CA057726. The Women's Health Initiative program is funded by the National Heart, Lung, and Blood Institute, NOH, US Department of Health and Human Services through contracts, HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. The development of Helicobacter pylori multiplex serology was funded in part by the Joint Initiative for Innovation and Research of the German Helmholtz Association. The funding sources played no role in the analysis or interpretation of the data. Study sponsor had no role in the study design or collection, analysis, or interpretation of the data.
Publisher Copyright:
© 2019 AGA Institute
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
KW - Cohort Studies
KW - Epidemiology
KW - Gastrointestinal Cancers
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U2 - 10.1053/j.gastro.2018.09.054
DO - 10.1053/j.gastro.2018.09.054
M3 - Article
C2 - 30296434
AN - SCOPUS:85058455264
SN - 0016-5085
VL - 156
SP - 175-186.e2
JO - Gastroenterology
JF - Gastroenterology
IS - 1
ER -