Abstract LB-361: Serology of Streptococcus gallolyticus subsp. gallolyticus and risk of colorectal cancer (2016)

Abstract Background: The colonic opportunist Streptococcus gallolyticus subsp. gallolyticus (S. gallolyticus) has been hypothesized to be associated with colorectal cancer (CRC). A recent case-control study (Butt et al., Int J Cancer. 2015 doi: 10.1002/ijc.29914.) showed an association of high antibody levels to S. gallolyticus pilus proteins with prevalent CRC. However, no study has yet explored this association in a prospective study. Objective: To determine whether antibody responses to S. gallolyticus are associated with CRC risk 1 to 8 (median 3) years before diagnosis. Methods: A case-control study was nested within the prospective Southern Community Cohort Study (SCCS) which has enrolled 86,000 men and women between 2002 and 2009 primarily from community health centers (CHC). Participants included here comprised 181 incident CRC cases that were identified until end of 2011 and 348 controls matched by sex, age, race, menopausal status, CHC site and date of blood collection. Antibodies to 11 recombinant affinity-purified S. gallolyticus proteins, including 4 S. gallolyticus pilus proteins, were quantified by multiplex serology. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. Results: Overall, there was no significant association of high antibody levels to any S. gallolyticus protein (OR: 1.11, 95% CI: 0.77-1.58) or any pilus protein (OR: 1.34, 95% CI: 0.91-1.96) with CRC. However, when stratifying by stage at diagnosis, the association with high antibody levels to any pilus protein was significant for CRC diagnosed with regional or distant stage (OR: 1.68, 95% CI: 1.01-2.78), whereby no association was found for localized CRC (OR: 0.85, 95% CI: 0.45-1.63). Epplein et al. showed that seropositivity to the gastric cancer virulence factor Helicobacter pylori (H. pylori) VacA is significantly associated with CRC (Epplein et al., Cancer Epidemiol Biomarkers Prev. 22(11):1964-74. 2013). Under the assumption that different bacteria may be involved in CRC and that they may interact with each other, we performed an analysis stratified by H. pylori VacA serostatus. Here, the association with high antibody levels to any S. gallolyticus protein with CRC was significant among H. pylori VacA negative individuals (OR: 2.40, 95% CI: 1.12-5.15) but absent among H. pylori VacA positives (OR: 0.83, 95% CI: 0.54-1.29; interaction p = 0.019). Conclusion: This prospective study failed to find a significant overall association of antibodies to S. gallolyticus proteins with CRC. However, among individuals (and their matched controls) who would go on to be diagnosed with later stage tumors, seropositivity to S. gallolyticus was associated with a significant 1.7-fold increase in risk for CRC. In addition we found an interaction between seropositivity to H. pylori VacA with S. gallolyticus in the association with CRC, whereby the increase in risk for seropositivity to S. gallolyticus was seen only among individuals not also infected with VacA-positive H. pylori. This finding supports the idea that different bacteria are involved in CRC and that they may influence each other in their association. Further research with larger study sizes is needed to examine the outcome by both time from blood collection to diagnosis and stage to more precisely shed light on the timing of the association, as well as to consider interaction with infection by other bacteria. Citation Format: Julia Butt, Michael Pawlita, Meira Epplein. Serology of Streptococcus gallolyticus subsp. gallolyticus and risk of colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-361.