Prospective evaluation of antibody response to Streptococcus gallolyticus and risk of colorectal cancer

Julia Butt, Mazda Jenab, Martina Willhauck-Fleckenstein, Angelika Michel, Michael Pawlita, Cecilie Kyrø, Anne Tjønneland, Marie-Christine Boutron-Ruault, Franck Carbonnel, Gianluca Severi, Rudolf Kaaks, Tilman Kühn, Heiner Boeing, Antonia Trichopoulou, Carlo la Vecchia, Anna Karakatsani, Salvatore Panico, Rosario Tumino, Claudia Agnoli, Domenico PalliCarlotta Sacerdote, H B As Bueno-de-Mesquita, Elisabete Weiderpass, Maria-José Sánchez, Catalina Bonet Bonet, José María Huerta, Eva Ardanaz, Kathryn Bradbury, Marc Gunter, Neil Murphy, Heinz Freisling, Elio Riboli, Kostas Tsilidis, Dagfinn Aune, Tim Waterboer, David J Hughes

Research output: Contribution to journalArticle

Abstract

The gut microbiome is increasingly implicated in colorectal cancer (CRC) development. A subgroup of patients diagnosed with CRC show high antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG). However, it is unclear whether the association is also present pre-diagnostically. We assessed the association of antibody responses to SGG proteins in pre-diagnostic serum samples with CRC risk in a case-control study nested within a prospective cohort. Pre-diagnostic serum samples from 485 first incident CRC cases (mean time between blood draw and diagnosis 3.4 years) and 485 matched controls in the European Prospective Investigation into Nutrition and Cancer (EPIC) study were analyzed for antibody responses to 11 SGG proteins using multiplex serology. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable conditional logistic regression models. Antibody positivity for any of the 11 SGG proteins was significantly associated with CRC risk with 56% positive controls compared to 63% positive cases (OR: 1.36, 95% CI: 1.04-1.77). Positivity for two or more proteins of a previously identified SGG 6-marker panel with greater CRC-specificity was also observed among 9% of controls compared to 17% of CRC cases, corresponding to a significantly increased CRC risk (OR: 2.17, 95% CI: 1.44-3.27). In this prospective nested case-control study, we observed a positive association between antibody responses to SGG and CRC development in serum samples taken before evident disease onset. Further work is required to establish the possibly etiological significance of these observations and whether SGG serology may be applicable for CRC risk stratification.

Original languageEnglish
Pages (from-to)245-252
Number of pages8
JournalInternational Journal of Cancer
Volume143
Issue number2
DOIs
Publication statusPublished - Jul 15 2018

Fingerprint

Antibody Formation
Colorectal Neoplasms
Odds Ratio
Confidence Intervals
Serology
Case-Control Studies
Proteins
Logistic Models
Serum
Streptococcus gallolyticus
Streptococcus gallolyticus subspecies gallolyticus
Antibodies

Keywords

  • Adult
  • Aged
  • Antibodies, Bacterial/metabolism
  • Bacterial Proteins/blood
  • Case-Control Studies
  • Colorectal Neoplasms/epidemiology
  • Female
  • Gastrointestinal Microbiome
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Prospective Studies
  • Streptococcal Infections/immunology
  • Streptococcus gallolyticus subspecies gallolyticus/immunology

Cite this

Butt, J., Jenab, M., Willhauck-Fleckenstein, M., Michel, A., Pawlita, M., Kyrø, C., ... Hughes, D. J. (2018). Prospective evaluation of antibody response to Streptococcus gallolyticus and risk of colorectal cancer. International Journal of Cancer, 143(2), 245-252. https://doi.org/10.1002/ijc.31283

Prospective evaluation of antibody response to Streptococcus gallolyticus and risk of colorectal cancer. / Butt, Julia; Jenab, Mazda; Willhauck-Fleckenstein, Martina; Michel, Angelika; Pawlita, Michael; Kyrø, Cecilie; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Carbonnel, Franck; Severi, Gianluca; Kaaks, Rudolf; Kühn, Tilman; Boeing, Heiner; Trichopoulou, Antonia; la Vecchia, Carlo; Karakatsani, Anna; Panico, Salvatore; Tumino, Rosario; Agnoli, Claudia; Palli, Domenico; Sacerdote, Carlotta; Bueno-de-Mesquita, H B As; Weiderpass, Elisabete; Sánchez, Maria-José; Bonet Bonet, Catalina; Huerta, José María; Ardanaz, Eva; Bradbury, Kathryn; Gunter, Marc; Murphy, Neil; Freisling, Heinz; Riboli, Elio; Tsilidis, Kostas; Aune, Dagfinn; Waterboer, Tim; Hughes, David J.

In: International Journal of Cancer, Vol. 143, No. 2, 15.07.2018, p. 245-252.

Research output: Contribution to journalArticle

Butt, J, Jenab, M, Willhauck-Fleckenstein, M, Michel, A, Pawlita, M, Kyrø, C, Tjønneland, A, Boutron-Ruault, M-C, Carbonnel, F, Severi, G, Kaaks, R, Kühn, T, Boeing, H, Trichopoulou, A, la Vecchia, C, Karakatsani, A, Panico, S, Tumino, R, Agnoli, C, Palli, D, Sacerdote, C, Bueno-de-Mesquita, HBA, Weiderpass, E, Sánchez, M-J, Bonet Bonet, C, Huerta, JM, Ardanaz, E, Bradbury, K, Gunter, M, Murphy, N, Freisling, H, Riboli, E, Tsilidis, K, Aune, D, Waterboer, T & Hughes, DJ 2018, 'Prospective evaluation of antibody response to Streptococcus gallolyticus and risk of colorectal cancer', International Journal of Cancer, vol. 143, no. 2, pp. 245-252. https://doi.org/10.1002/ijc.31283
Butt, Julia ; Jenab, Mazda ; Willhauck-Fleckenstein, Martina ; Michel, Angelika ; Pawlita, Michael ; Kyrø, Cecilie ; Tjønneland, Anne ; Boutron-Ruault, Marie-Christine ; Carbonnel, Franck ; Severi, Gianluca ; Kaaks, Rudolf ; Kühn, Tilman ; Boeing, Heiner ; Trichopoulou, Antonia ; la Vecchia, Carlo ; Karakatsani, Anna ; Panico, Salvatore ; Tumino, Rosario ; Agnoli, Claudia ; Palli, Domenico ; Sacerdote, Carlotta ; Bueno-de-Mesquita, H B As ; Weiderpass, Elisabete ; Sánchez, Maria-José ; Bonet Bonet, Catalina ; Huerta, José María ; Ardanaz, Eva ; Bradbury, Kathryn ; Gunter, Marc ; Murphy, Neil ; Freisling, Heinz ; Riboli, Elio ; Tsilidis, Kostas ; Aune, Dagfinn ; Waterboer, Tim ; Hughes, David J. / Prospective evaluation of antibody response to Streptococcus gallolyticus and risk of colorectal cancer. In: International Journal of Cancer. 2018 ; Vol. 143, No. 2. pp. 245-252.
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AB - The gut microbiome is increasingly implicated in colorectal cancer (CRC) development. A subgroup of patients diagnosed with CRC show high antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG). However, it is unclear whether the association is also present pre-diagnostically. We assessed the association of antibody responses to SGG proteins in pre-diagnostic serum samples with CRC risk in a case-control study nested within a prospective cohort. Pre-diagnostic serum samples from 485 first incident CRC cases (mean time between blood draw and diagnosis 3.4 years) and 485 matched controls in the European Prospective Investigation into Nutrition and Cancer (EPIC) study were analyzed for antibody responses to 11 SGG proteins using multiplex serology. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable conditional logistic regression models. Antibody positivity for any of the 11 SGG proteins was significantly associated with CRC risk with 56% positive controls compared to 63% positive cases (OR: 1.36, 95% CI: 1.04-1.77). Positivity for two or more proteins of a previously identified SGG 6-marker panel with greater CRC-specificity was also observed among 9% of controls compared to 17% of CRC cases, corresponding to a significantly increased CRC risk (OR: 2.17, 95% CI: 1.44-3.27). In this prospective nested case-control study, we observed a positive association between antibody responses to SGG and CRC development in serum samples taken before evident disease onset. Further work is required to establish the possibly etiological significance of these observations and whether SGG serology may be applicable for CRC risk stratification.

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KW - Aged

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KW - Case-Control Studies

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KW - Female

KW - Gastrointestinal Microbiome

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KW - Male

KW - Middle Aged

KW - Odds Ratio

KW - Prospective Studies

KW - Streptococcal Infections/immunology

KW - Streptococcus gallolyticus subspecies gallolyticus/immunology

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