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, So Yeon
AU - Tran, Hao Quang
AU - Gewirtz, Andrew T.
AU - McKeown-Eyssen, Gail
AU - Fedirko, Veronika
AU - Romieu, Isabelle
AU - Tjønneland, Anne
AU - Olsen, Anja
AU - Overvad, Kim
AU - Boutron-Ruault, Marie Christine
AU - Bastide, Nadia
AU - Affret, Aurélie
AU - Kühn, Tilman
AU - Kaaks, Rudolf
AU - Boeing, Heiner
AU - Aleksandrova, Krasimira
AU - Trichopoulou, Antonia
AU - Kritikou, Maria
AU - Vasilopoulou, Effie
AU - Palli, Domenico
AU - Krogh, Vittorio
AU - Mattiello, Amalia
AU - Tumino, Rosario
AU - Naccarati, Alessio
AU - Bueno-De-mesquita, H. B.
AU - Peeters, Petra H.
AU - Weiderpass, Elisabete
AU - Quirós, J. Ramón
AU - Sala, Núria
AU - Sánchez, María José
AU - Castanõ, José María Huerta
AU - Barricarte, Aurelio
AU - Dorronsoro, Miren
AU - Werner, Marten
AU - Wareham, Nicholas J.
AU - Khaw, Kay Tee
AU - Bradbury, Kathryn E.
AU - Freisling, Heinz
AU - Stavropoulou, Faidra
AU - Ferrari, Pietro
AU - Gunter, Marc J.
AU - Cross, Amanda J.
AU - Riboli, Elio
AU - Bruce, W. Robert
AU - Jenab, Mazda
PY - 2016/2/1
Y1 - 2016/2/1
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 = 667; rectal, n = 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 biomarker levels were not associated with colorectal cancer risk. After testing potential 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 all the 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 anti- LPS 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 these preliminary 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 = 667; rectal, n = 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 biomarker levels were not associated with colorectal cancer risk. After testing potential 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 all the 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 anti- LPS 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 these preliminary observations.
UR - http://www.scopus.com/inward/record.url?scp=84957801112&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-15-0798
DO - 10.1158/1055-9965.EPI-15-0798
M3 - Article
C2 - 26823475
AN - SCOPUS:84957801112
SN - 1055-9965
VL - 25
SP - 291
EP - 301
JO - Cancer Epidemiology Biomarkers & Prevention
JF - Cancer Epidemiology Biomarkers & Prevention
IS - 2
ER -