Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

S. Y. Kong; H. Q. Tran; A. T. Gewirtz; G. McKeown-Eyssen; V. Fedirko; I. Romieu; A. Tjonneland; A. Olsen; K. Overvad; M. C. Boutron-Ruault; N. Bastide; A. Affret; T. Kuhn; R. Kaaks; H. Boeing; K. Aleksandrova; A. Trichopoulou; M. Kritikou; E. Vasilopoulou; D. Palli; V. Krogh; A. Mattiello; R. Tumino; A. Naccarati; H. B. Bueno-de-Mesquita; P. H. Peeters; E. Weiderpass; J. R. Quiros; N. Sala; M. J. Sanchez; J. M. Castano; A. Barricarte; M. Dorronsoro; M. Werner; N. J. Wareham; K. T. Khaw; K. E. Bradbury; H. Freisling; F. Stavropoulou; P. Ferrari; M. J. Gunter; A. J. Cross; E. Riboli; W. R. Bruce; M. Jenab

doi:10.1158/1055-9965.Epi-15-0798

Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

S. Y. Kong, H. Q. Tran, A. T. Gewirtz, G. McKeown-Eyssen, V. Fedirko, I. Romieu, A. Tjonneland, A. Olsen, K. Overvad, M. C. Boutron-Ruault, N. Bastide, A. Affret, T. Kuhn, R. Kaaks, H. Boeing, K. Aleksandrova, A. Trichopoulou, M. Kritikou, E. Vasilopoulou, D. PalliV. Krogh, A. Mattiello, R. Tumino, A. Naccarati, H. B. Bueno-de-Mesquita, P. H. Peeters, E. Weiderpass, J. R. Quiros, N. Sala, M. J. Sanchez, J. M. Castano, A. Barricarte, M. Dorronsoro, M. Werner, N. J. Wareham, K. T. Khaw, K. E. Bradbury, H. Freisling, F. Stavropoulou, P. Ferrari, M. J. Gunter, A. J. Cross, E. Riboli, W. R. Bruce, M. Jenab

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

Background: Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer development. These processes may contribute to leakage of bacterial products, such as lipopolysaccharide (LPS) and flagellin, across the gut barrier. The objective of this study, nested within a prospective cohort, was to examine associations between circulating LPS and flagellin serum antibody levels and colorectal cancer risk.Methods: A total of 1,065 incident colorectal cancer cases(colon, n ¼ 667; rectal, n ¼ 398) were matched (1:1) to control subjects. Serum flagellin- and LPS-specific IgA and IgG levels were quantitated by ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI), adjusting for multiple relevant confouding factors.Results: Overall, elevated anti-LPS and anti-flagellin biomarkerlevels were not associated with colorectal cancer risk. After testingpotential interactions by various factors relevant for colorectal cancer risk and anti-LPS and anti-flagellin, sex was identified as a statistically significant interaction factor (Pinteraction < 0.05 for allthe biomarkers). Analyses stratified by sex showed a statistically significant positive colorectal cancer risk association for men(fully-adjusted OR for highest vs. lowest quartile for total antiLPS þ flagellin, 1.66; 95% CI, 1.10–2.51; Ptrend, 0.049), whereas a borderline statistically significant inverse association was observed for women (fully-adjusted OR, 0.70; 95% CI, 0.47–1.02; Ptrend, 0.18).Conclusion: In this prospective study on European populations, we found bacterial exposure levels to be positively associated to colorectal cancer risk among men, whereas in women, a possible inverse association may exist.Impact: Further studies are warranted to better clarify thesepreliminary observations.

Original language	Undefined/Unknown
Pages (from-to)	291-301
Number of pages	11
Journal	Cancer Epidemiology Biomarkers & Prevention
Volume	25
Issue number	2
DOIs	https://doi.org/10.1158/1055-9965.Epi-15-0798
Publication status	Published - Feb 2016

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Kong, S. Y., Tran, H. Q., Gewirtz, A. T., McKeown-Eyssen, G., Fedirko, V., Romieu, I., Tjonneland, A., Olsen, A., Overvad, K., Boutron-Ruault, M. C., Bastide, N., Affret, A., Kuhn, T., Kaaks, R., Boeing, H., Aleksandrova, K., Trichopoulou, A., Kritikou, M., Vasilopoulou, E., ... Jenab, M. (2016). Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort. Cancer Epidemiology Biomarkers & Prevention, 25(2), 291-301. https://doi.org/10.1158/1055-9965.Epi-15-0798

@article{134a3a7a6de34e21a2f2ce4fd9383452,

title = "Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort",

abstract = "Background: Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer development. These processes may contribute to leakage of bacterial products, such as lipopolysaccharide (LPS) and flagellin, across the gut barrier. The objective of this study, nested within a prospective cohort, was to examine associations between circulating LPS and flagellin serum antibody levels and colorectal cancer risk.Methods: A total of 1,065 incident colorectal cancer cases(colon, n ¼ 667; rectal, n ¼ 398) were matched (1:1) to control subjects. Serum flagellin- and LPS-specific IgA and IgG levels were quantitated by ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI), adjusting for multiple relevant confouding factors.Results: Overall, elevated anti-LPS and anti-flagellin biomarkerlevels were not associated with colorectal cancer risk. After testingpotential interactions by various factors relevant for colorectal cancer risk and anti-LPS and anti-flagellin, sex was identified as a statistically significant interaction factor (Pinteraction < 0.05 for allthe biomarkers). Analyses stratified by sex showed a statistically significant positive colorectal cancer risk association for men(fully-adjusted OR for highest vs. lowest quartile for total antiLPS {\th} flagellin, 1.66; 95% CI, 1.10–2.51; Ptrend, 0.049), whereas a borderline statistically significant inverse association was observed for women (fully-adjusted OR, 0.70; 95% CI, 0.47–1.02; Ptrend, 0.18).Conclusion: In this prospective study on European populations, we found bacterial exposure levels to be positively associated to colorectal cancer risk among men, whereas in women, a possible inverse association may exist.Impact: Further studies are warranted to better clarify thesepreliminary observations. ",

author = "Kong, {S. Y.} and Tran, {H. Q.} and Gewirtz, {A. T.} and G. McKeown-Eyssen and V. Fedirko and I. Romieu and A. Tjonneland and A. Olsen and K. Overvad and Boutron-Ruault, {M. C.} and N. Bastide and A. Affret and T. Kuhn and R. Kaaks and H. Boeing and K. Aleksandrova and A. Trichopoulou and M. Kritikou and E. Vasilopoulou and D. Palli and V. Krogh and A. Mattiello and R. Tumino and A. Naccarati and Bueno-de-Mesquita, {H. B.} and Peeters, {P. H.} and E. Weiderpass and Quiros, {J. R.} and N. Sala and Sanchez, {M. J.} and Castano, {J. M.} and A. Barricarte and M. Dorronsoro and M. Werner and Wareham, {N. J.} and Khaw, {K. T.} and Bradbury, {K. E.} and H. Freisling and F. Stavropoulou and P. Ferrari and Gunter, {M. J.} and Cross, {A. J.} and E. Riboli and Bruce, {W. R.} and M. Jenab",

year = "2016",

month = feb,

doi = "10.1158/1055-9965.Epi-15-0798",

language = "Undefined/Unknown",

volume = "25",

pages = "291--301",

journal = "Cancer Epidemiology Biomarkers & Prevention",

issn = "1055-9965",

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

number = "2",

}

Kong, SY, Tran, HQ, Gewirtz, AT, McKeown-Eyssen, G, Fedirko, V, Romieu, I, Tjonneland, A, Olsen, A, Overvad, K, Boutron-Ruault, MC, Bastide, N, Affret, A, Kuhn, T, Kaaks, R, Boeing, H, Aleksandrova, K, Trichopoulou, A, Kritikou, M, Vasilopoulou, E, Palli, D, Krogh, V, Mattiello, A, Tumino, R, Naccarati, A, Bueno-de-Mesquita, HB, Peeters, PH, Weiderpass, E, Quiros, JR, Sala, N, Sanchez, MJ, Castano, JM, Barricarte, A, Dorronsoro, M, Werner, M, Wareham, NJ, Khaw, KT, Bradbury, KE, Freisling, H, Stavropoulou, F, Ferrari, P, Gunter, MJ, Cross, AJ, Riboli, E, Bruce, WR & Jenab, M 2016, 'Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort', Cancer Epidemiology Biomarkers & Prevention, vol. 25, no. 2, pp. 291-301. https://doi.org/10.1158/1055-9965.Epi-15-0798

TY - JOUR

T1 - Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

AU - Kong, S. Y.

AU - Tran, H. Q.

AU - Gewirtz, A. T.

AU - McKeown-Eyssen, G.

AU - Fedirko, V.

AU - Romieu, I.

AU - Tjonneland, A.

AU - Olsen, A.

AU - Overvad, K.

AU - Boutron-Ruault, M. C.

AU - Bastide, N.

AU - Affret, A.

AU - Kuhn, T.

AU - Kaaks, R.

AU - Boeing, H.

AU - Aleksandrova, K.

AU - Trichopoulou, A.

AU - Kritikou, M.

AU - Vasilopoulou, E.

AU - Palli, D.

AU - Krogh, V.

AU - Mattiello, A.

AU - Tumino, R.

AU - Naccarati, A.

AU - Bueno-de-Mesquita, H. B.

AU - Peeters, P. H.

AU - Weiderpass, E.

AU - Quiros, J. R.

AU - Sala, N.

AU - Sanchez, M. J.

AU - Castano, J. M.

AU - Barricarte, A.

AU - Dorronsoro, M.

AU - Werner, M.

AU - Wareham, N. J.

AU - Khaw, K. T.

AU - Bradbury, K. E.

AU - Freisling, H.

AU - Stavropoulou, F.

AU - Ferrari, P.

AU - Gunter, M. J.

AU - Cross, A. J.

AU - Riboli, E.

AU - Bruce, W. R.

AU - Jenab, M.

PY - 2016/2

Y1 - 2016/2

N2 - Background: Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer development. These processes may contribute to leakage of bacterial products, such as lipopolysaccharide (LPS) and flagellin, across the gut barrier. The objective of this study, nested within a prospective cohort, was to examine associations between circulating LPS and flagellin serum antibody levels and colorectal cancer risk.Methods: A total of 1,065 incident colorectal cancer cases(colon, n ¼ 667; rectal, n ¼ 398) were matched (1:1) to control subjects. Serum flagellin- and LPS-specific IgA and IgG levels were quantitated by ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI), adjusting for multiple relevant confouding factors.Results: Overall, elevated anti-LPS and anti-flagellin biomarkerlevels were not associated with colorectal cancer risk. After testingpotential interactions by various factors relevant for colorectal cancer risk and anti-LPS and anti-flagellin, sex was identified as a statistically significant interaction factor (Pinteraction < 0.05 for allthe biomarkers). Analyses stratified by sex showed a statistically significant positive colorectal cancer risk association for men(fully-adjusted OR for highest vs. lowest quartile for total antiLPS þ flagellin, 1.66; 95% CI, 1.10–2.51; Ptrend, 0.049), whereas a borderline statistically significant inverse association was observed for women (fully-adjusted OR, 0.70; 95% CI, 0.47–1.02; Ptrend, 0.18).Conclusion: In this prospective study on European populations, we found bacterial exposure levels to be positively associated to colorectal cancer risk among men, whereas in women, a possible inverse association may exist.Impact: Further studies are warranted to better clarify thesepreliminary observations.

AB - Background: Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer development. These processes may contribute to leakage of bacterial products, such as lipopolysaccharide (LPS) and flagellin, across the gut barrier. The objective of this study, nested within a prospective cohort, was to examine associations between circulating LPS and flagellin serum antibody levels and colorectal cancer risk.Methods: A total of 1,065 incident colorectal cancer cases(colon, n ¼ 667; rectal, n ¼ 398) were matched (1:1) to control subjects. Serum flagellin- and LPS-specific IgA and IgG levels were quantitated by ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI), adjusting for multiple relevant confouding factors.Results: Overall, elevated anti-LPS and anti-flagellin biomarkerlevels were not associated with colorectal cancer risk. After testingpotential interactions by various factors relevant for colorectal cancer risk and anti-LPS and anti-flagellin, sex was identified as a statistically significant interaction factor (Pinteraction < 0.05 for allthe biomarkers). Analyses stratified by sex showed a statistically significant positive colorectal cancer risk association for men(fully-adjusted OR for highest vs. lowest quartile for total antiLPS þ flagellin, 1.66; 95% CI, 1.10–2.51; Ptrend, 0.049), whereas a borderline statistically significant inverse association was observed for women (fully-adjusted OR, 0.70; 95% CI, 0.47–1.02; Ptrend, 0.18).Conclusion: In this prospective study on European populations, we found bacterial exposure levels to be positively associated to colorectal cancer risk among men, whereas in women, a possible inverse association may exist.Impact: Further studies are warranted to better clarify thesepreliminary observations.

U2 - 10.1158/1055-9965.Epi-15-0798

DO - 10.1158/1055-9965.Epi-15-0798

M3 - Article

SN - 1055-9965

VL - 25

SP - 291

EP - 301

JO - Cancer Epidemiology Biomarkers & Prevention

JF - Cancer Epidemiology Biomarkers & Prevention

IS - 2

ER -