Antibody responses to Helicobacter pylori and risk of developing colorectal cancer in a European cohort

Julia Butt; Mazda Jenab; Michael Pawlita; Anne Tjonneland; Cecilie Kyrø; Marie-Christine Boutron-Ruault; Franck Carbonnel; Catherine Dong; Rudolf Kaaks; Tilman Kühn; Heiner Boeing; Matthias B Schulze; Antonia Trichopoulou; Anna Karakatsani; Carlo La Vecchia; Domenico Palli; Claudia Agnoli; Rosario Tumino; Carlotta Sacerdote; Salvatore Panico; Bas Bueno-de-Mesquita; Roel Vermeulen; Inger T Gram; Elisabete Weiderpass; Kristin Benjaminsen Borch; J Ramón Quirós; Antonio Agudo; Miguel Rodríguez-Barranco; Carmen Santiuste; Eva Ardanaz; Bethany Van Guelpen; Sophia Harlid; Liher Imaz; Aurora Perez-Cornago; Marc J Gunter; Semi Zouiouich; Jin Young Park; Elio Riboli; Amanda J Cross; Alicia K Heath; Tim Waterboer; David J Hughes

doi:10.1158/1055-9965.EPI-19-1545

Antibody responses to Helicobacter pylori and risk of developing colorectal cancer in a European cohort

Julia Butt, Mazda Jenab, Michael Pawlita, Anne Tjonneland, Cecilie Kyrø, Marie-Christine Boutron-Ruault, Franck Carbonnel, Catherine Dong, Rudolf Kaaks, Tilman Kühn, Heiner Boeing, Matthias B Schulze, Antonia Trichopoulou, Anna Karakatsani, Carlo La Vecchia, Domenico Palli, Claudia Agnoli, Rosario Tumino, Carlotta Sacerdote, Salvatore PanicoBas Bueno-de-Mesquita, Roel Vermeulen, Inger T Gram, Elisabete Weiderpass, Kristin Benjaminsen Borch, J Ramón Quirós, Antonio Agudo, Miguel Rodríguez-Barranco, Carmen Santiuste, Eva Ardanaz, Bethany Van Guelpen, Sophia Harlid, Liher Imaz, Aurora Perez-Cornago, Marc J Gunter, Semi Zouiouich, Jin Young Park, Elio Riboli, Amanda J Cross, Alicia K Heath, Tim Waterboer, David J Hughes

School of Biological Sciences

Research output: Contribution to journal › Article

Abstract

BACKGROUND: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer (CRC) development. However, prospective studies addressing H. pylori and CRC are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

METHODS: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in pre-diagnostic serum samples from 485 CRC cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific sero-positivity with odds of developing CRC.

RESULTS: Fifty-one percent of CRC cases were H. pylori sero-positive compared to 44% of controls resulting in an OR of 1.36 (95% CI: 1.00-1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by sero-positivity to Helicobacter cysteine-rich protein C (HcpC) (OR: 1.66, 95% CI: 1.19-2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34, 95% CI: 0.99-1.82), the latter being non-statistically significant only in the fully adjusted model.

CONCLUSION: In this prospective multi-center European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing CRC.

IMPACT: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease CRC incidence.

Original language	English
Journal	Cancer Epidemiology Biomarkers & Prevention
Early online date	24 Apr 2020
DOIs	https://doi.org/10.1158/1055-9965.EPI-19-1545
Publication status	Early online date - 24 Apr 2020

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Butt, J., Jenab, M., Pawlita, M., Tjonneland, A., Kyrø, C., Boutron-Ruault, M-C., Carbonnel, F., Dong, C., Kaaks, R., Kühn, T., Boeing, H., Schulze, M. B., Trichopoulou, A., Karakatsani, A., La Vecchia, C., Palli, D., Agnoli, C., Tumino, R., Sacerdote, C., ... Hughes, D. J. (2020). Antibody responses to Helicobacter pylori and risk of developing colorectal cancer in a European cohort. Cancer Epidemiology Biomarkers & Prevention. https://doi.org/10.1158/1055-9965.EPI-19-1545

Butt, Julia ; Jenab, Mazda ; Pawlita, Michael ; Tjonneland, Anne ; Kyrø, Cecilie ; Boutron-Ruault, Marie-Christine ; Carbonnel, Franck ; Dong, Catherine ; Kaaks, Rudolf ; Kühn, Tilman ; Boeing, Heiner ; Schulze, Matthias B ; Trichopoulou, Antonia ; Karakatsani, Anna ; La Vecchia, Carlo ; Palli, Domenico ; Agnoli, Claudia ; Tumino, Rosario ; Sacerdote, Carlotta ; Panico, Salvatore ; Bueno-de-Mesquita, Bas ; Vermeulen, Roel ; Gram, Inger T ; Weiderpass, Elisabete ; Benjaminsen Borch, Kristin ; Quirós, J Ramón ; Agudo, Antonio ; Rodríguez-Barranco, Miguel ; Santiuste, Carmen ; Ardanaz, Eva ; Van Guelpen, Bethany ; Harlid, Sophia ; Imaz, Liher ; Perez-Cornago, Aurora ; Gunter, Marc J ; Zouiouich, Semi ; Park, Jin Young ; Riboli, Elio ; Cross, Amanda J ; Heath, Alicia K ; Waterboer, Tim ; Hughes, David J. / Antibody responses to Helicobacter pylori and risk of developing colorectal cancer in a European cohort. In: Cancer Epidemiology Biomarkers & Prevention. 2020.

@article{526d250dca184e6aaca03c8647ee3098,

title = "Antibody responses to Helicobacter pylori and risk of developing colorectal cancer in a European cohort",

abstract = "BACKGROUND: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer (CRC) development. However, prospective studies addressing H. pylori and CRC are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.METHODS: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in pre-diagnostic serum samples from 485 CRC cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific sero-positivity with odds of developing CRC.RESULTS: Fifty-one percent of CRC cases were H. pylori sero-positive compared to 44% of controls resulting in an OR of 1.36 (95% CI: 1.00-1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by sero-positivity to Helicobacter cysteine-rich protein C (HcpC) (OR: 1.66, 95% CI: 1.19-2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34, 95% CI: 0.99-1.82), the latter being non-statistically significant only in the fully adjusted model.CONCLUSION: In this prospective multi-center European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing CRC.IMPACT: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease CRC incidence.",

author = "Julia Butt and Mazda Jenab and Michael Pawlita and Anne Tjonneland and Cecilie Kyr{\o} and Marie-Christine Boutron-Ruault and Franck Carbonnel and Catherine Dong and Rudolf Kaaks and Tilman K{\"u}hn and Heiner Boeing and Schulze, {Matthias B} and Antonia Trichopoulou and Anna Karakatsani and {La Vecchia}, Carlo and Domenico Palli and Claudia Agnoli and Rosario Tumino and Carlotta Sacerdote and Salvatore Panico and Bas Bueno-de-Mesquita and Roel Vermeulen and Gram, {Inger T} and Elisabete Weiderpass and {Benjaminsen Borch}, Kristin and Quir{\'o}s, {J Ram{\'o}n} and Antonio Agudo and Miguel Rodr{\'i}guez-Barranco and Carmen Santiuste and Eva Ardanaz and {Van Guelpen}, Bethany and Sophia Harlid and Liher Imaz and Aurora Perez-Cornago and Gunter, {Marc J} and Semi Zouiouich and Park, {Jin Young} and Elio Riboli and Cross, {Amanda J} and Heath, {Alicia K} and Tim Waterboer and Hughes, {David J}",

note = "Copyright {\textcopyright}2020, American Association for Cancer Research.",

year = "2020",

month = apr,

day = "24",

doi = "10.1158/1055-9965.EPI-19-1545",

language = "English",

journal = "Cancer Epidemiology Biomarkers & Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

}

Butt, J, Jenab, M, Pawlita, M, Tjonneland, A, Kyrø, C, Boutron-Ruault, M-C, Carbonnel, F, Dong, C, Kaaks, R, Kühn, T, Boeing, H, Schulze, MB, Trichopoulou, A, Karakatsani, A, La Vecchia, C, Palli, D, Agnoli, C, Tumino, R, Sacerdote, C, Panico, S, Bueno-de-Mesquita, B, Vermeulen, R, Gram, IT, Weiderpass, E, Benjaminsen Borch, K, Quirós, JR, Agudo, A, Rodríguez-Barranco, M, Santiuste, C, Ardanaz, E, Van Guelpen, B, Harlid, S, Imaz, L, Perez-Cornago, A, Gunter, MJ, Zouiouich, S, Park, JY, Riboli, E, Cross, AJ, Heath, AK, Waterboer, T & Hughes, DJ 2020, 'Antibody responses to Helicobacter pylori and risk of developing colorectal cancer in a European cohort', Cancer Epidemiology Biomarkers & Prevention. https://doi.org/10.1158/1055-9965.EPI-19-1545

Antibody responses to Helicobacter pylori and risk of developing colorectal cancer in a European cohort. / Butt, Julia; Jenab, Mazda; Pawlita, Michael; Tjonneland, Anne; Kyrø, Cecilie; Boutron-Ruault, Marie-Christine; Carbonnel, Franck; Dong, Catherine; Kaaks, Rudolf; Kühn, Tilman; Boeing, Heiner; Schulze, Matthias B; Trichopoulou, Antonia; Karakatsani, Anna; La Vecchia, Carlo; Palli, Domenico; Agnoli, Claudia; Tumino, Rosario; Sacerdote, Carlotta; Panico, Salvatore; Bueno-de-Mesquita, Bas; Vermeulen, Roel; Gram, Inger T; Weiderpass, Elisabete; Benjaminsen Borch, Kristin; Quirós, J Ramón; Agudo, Antonio; Rodríguez-Barranco, Miguel; Santiuste, Carmen; Ardanaz, Eva; Van Guelpen, Bethany; Harlid, Sophia; Imaz, Liher; Perez-Cornago, Aurora; Gunter, Marc J; Zouiouich, Semi; Park, Jin Young; Riboli, Elio; Cross, Amanda J; Heath, Alicia K; Waterboer, Tim; Hughes, David J.

In: Cancer Epidemiology Biomarkers & Prevention, 24.04.2020.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Antibody responses to Helicobacter pylori and risk of developing colorectal cancer in a European cohort

AU - Butt, Julia

AU - Jenab, Mazda

AU - Pawlita, Michael

AU - Tjonneland, Anne

AU - Kyrø, Cecilie

AU - Boutron-Ruault, Marie-Christine

AU - Carbonnel, Franck

AU - Dong, Catherine

AU - Kaaks, Rudolf

AU - Kühn, Tilman

AU - Boeing, Heiner

AU - Schulze, Matthias B

AU - Trichopoulou, Antonia

AU - Karakatsani, Anna

AU - La Vecchia, Carlo

AU - Palli, Domenico

AU - Agnoli, Claudia

AU - Tumino, Rosario

AU - Sacerdote, Carlotta

AU - Panico, Salvatore

AU - Bueno-de-Mesquita, Bas

AU - Vermeulen, Roel

AU - Gram, Inger T

AU - Weiderpass, Elisabete

AU - Benjaminsen Borch, Kristin

AU - Quirós, J Ramón

AU - Agudo, Antonio

AU - Rodríguez-Barranco, Miguel

AU - Santiuste, Carmen

AU - Ardanaz, Eva

AU - Van Guelpen, Bethany

AU - Harlid, Sophia

AU - Imaz, Liher

AU - Perez-Cornago, Aurora

AU - Gunter, Marc J

AU - Zouiouich, Semi

AU - Park, Jin Young

AU - Riboli, Elio

AU - Cross, Amanda J

AU - Heath, Alicia K

AU - Waterboer, Tim

AU - Hughes, David J

PY - 2020/4/24

Y1 - 2020/4/24

N2 - BACKGROUND: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer (CRC) development. However, prospective studies addressing H. pylori and CRC are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.METHODS: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in pre-diagnostic serum samples from 485 CRC cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific sero-positivity with odds of developing CRC.RESULTS: Fifty-one percent of CRC cases were H. pylori sero-positive compared to 44% of controls resulting in an OR of 1.36 (95% CI: 1.00-1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by sero-positivity to Helicobacter cysteine-rich protein C (HcpC) (OR: 1.66, 95% CI: 1.19-2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34, 95% CI: 0.99-1.82), the latter being non-statistically significant only in the fully adjusted model.CONCLUSION: In this prospective multi-center European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing CRC.IMPACT: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease CRC incidence.

AB - BACKGROUND: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer (CRC) development. However, prospective studies addressing H. pylori and CRC are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.METHODS: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in pre-diagnostic serum samples from 485 CRC cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific sero-positivity with odds of developing CRC.RESULTS: Fifty-one percent of CRC cases were H. pylori sero-positive compared to 44% of controls resulting in an OR of 1.36 (95% CI: 1.00-1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by sero-positivity to Helicobacter cysteine-rich protein C (HcpC) (OR: 1.66, 95% CI: 1.19-2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34, 95% CI: 0.99-1.82), the latter being non-statistically significant only in the fully adjusted model.CONCLUSION: In this prospective multi-center European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing CRC.IMPACT: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease CRC incidence.

U2 - 10.1158/1055-9965.EPI-19-1545

DO - 10.1158/1055-9965.EPI-19-1545

M3 - Article

C2 - 32332031

JO - Cancer Epidemiology Biomarkers & Prevention

JF - Cancer Epidemiology Biomarkers & Prevention

SN - 1055-9965

ER -