ASPO Abstracts

Antibody responses to Streptococcus gallolyticus subspecies gallolyticus proteins in a large prospective colorectal cancer cohort consortium

Authors: Butt J, Blot W, Teras L, Visvanathan K, Marchand L, Chen Y, Bao Y, Sesso HD, Wassertheil-Smoller S, Ho G, Tinker L, Peek R, Potter J, Waterboer T, Epplein M

Category: Molecular Epidemiology & Environment, Early Detection & Risk Prediction
Conference Year: 2018

Abstract Body:
Purpose: Antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG) proteins, especially pilus protein Gallo2178, have been consistently associated with colorectal cancer (CRC) risk. Previous case-control studies and prospective studies with up to 8 years of follow-up limited the interpretation of SGG infection as a cause or consequence in CRC development. We aimed to analyze a large US CRC cohort consortium with follow-up of up to 40 years for antibody responses to SGG. Methods: We applied multiplex serology to measure antibody responses to 9 SGG proteins in serum samples of participants in 10 prospective US cohorts (CLUE, CPSII, HPFS, MEC, NHS, NYUWHS, PHS, PLCO, SCCS and WHI) including 4,063 incident CRC cases and 4,063 matched controls. SGG sero-positivity was defined as a median fluorescence intensity (MFI) value above the antigen-specific cut-off and indicates past and/or current infection. Conditional logistic regression was used to assess whether antibody responses to SGG are associated with the risk of developing CRC, overall and by time between blood draw to diagnosis. Results: CRC risk was increased with antibody responses to Gallo2178 only, albeit not significantly (OR: 1.23; 95% CI: 0.99-1.52). This association became stronger for CRC cases diagnosed less than 10 years after blood draw (OR: 1.40; 95% CI: 1.09-1.79), but not among CRC cases diagnosed more than 10 years after blood draw (OR: 0.79; 95% CI: 0.50-1.24). Conclusion: In this CRC cohort consortium, we reproduced the association of antibody responses to SGG pilus protein Gallo2178 with risk of developing CRC, but only among those individuals diagnosed within 10 years of their blood draw. These data support the hypothesis of SGG infection as a consequence of tumor development. However, the possibility of SGG also acting as a promotor after initiation of carcinogenesis cannot be excluded.

Keywords: Colorectal cancer, infection, serology, Streptococcus gallolyticus, cohort study