Pre-diagnostic plasma bile acid levels and colon cancer risk: A prospective study

Tilman Kühn; Magdalena Stepien; Marina López-Nogueroles; Antje Damms Machado; Disorn Sookthai; Theron Johnson; Marta Roca; Anika Hüsing; Sandra González Maldonado; Amanda J Cross; Neil Murphy; Heinz Freisling; Sabina Rinaldi; Augustin Scalbert; Veronika Fedirco; Gianluca Severi; Marie-Christine Boutron-Ruault; Francesca Romana Mancini; Solomon A Sowah; Heiner Boeing; Paula Jakszyn; Maria-Jose Sánchez; Susana Merino; Sandra Colorado-Yohar; Aurelio Barricarte; Kay Tee Khaw; Julie A Schmidt; Aurora Perez-Cornago; Antonia Trichopoulou; Anna Karakatsani; Paschalis Thriskos; Domenico Palli; Claudia Agnoli; Rosario Tumino; Carlotta Sacerdote; Salvatore Panico; Bas Bueno-de-Mesquita; Carla H van Gils; Alicia Heath; Marc J Gunter; Elio Riboli; Agustín Lahoz; Mazda Jenab; Rudolf Kaaks

doi:10.1093/jnci/djz166

Pre-diagnostic plasma bile acid levels and colon cancer risk: A prospective study

Tilman Kühn, Magdalena Stepien, Marina López-Nogueroles, Antje Damms Machado, Disorn Sookthai, Theron Johnson, Marta Roca, Anika Hüsing, Sandra González Maldonado, Amanda J Cross, Neil Murphy, Heinz Freisling, Sabina Rinaldi, Augustin Scalbert, Veronika Fedirco, Gianluca Severi, Marie-Christine Boutron-Ruault, Francesca Romana Mancini, Solomon A Sowah, Heiner BoeingPaula Jakszyn, Maria-Jose Sánchez, Susana Merino, Sandra Colorado-Yohar, Aurelio Barricarte, Kay Tee Khaw, Julie A Schmidt, Aurora Perez-Cornago, Antonia Trichopoulou, Anna Karakatsani, Paschalis Thriskos, Domenico Palli, Claudia Agnoli, Rosario Tumino, Carlotta Sacerdote, Salvatore Panico, Bas Bueno-de-Mesquita, Carla H van Gils, Alicia Heath, Marc J Gunter, Elio Riboli, Agustín Lahoz, Mazda Jenab, Rudolf Kaaks

School of Biological Sciences

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

87 Citations (Scopus)

Abstract

BACKGROUND: Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans.

METHODS: Associations between pre-diagnostic plasma levels of 17 primary, secondary and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations.

RESULTS: Positive associations were observed between colon cancer risk and plasma levels of 7 conjugated bile acid metabolites, i.e. primary bile acids glycocholic acid (ORQuartile 4 vs. Quartile 1=2.22,95 % confidence interval[CI]=1.52, 3.26), taurocholic acid (OR = 1.78, 95%CI=1.23, 2.58), glycochenodeoxycholic acid (OR = 1.68, 95%CI=1.13, 2.48), taurochenodeoxycholic acid (OR = 1.62, 95%CI=1.11-2.36), and glycohyocholic acid (OR = 1.65, 95%CI=1.13, 2.40) as well as the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95%CI=1.12, 2.54) and taurodeoxycholic acid (OR = 1.54, 95%CI=1.02, 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk.

CONCLUSIONS: This prospective study showed that pre-diagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.

Original language	English
Pages (from-to)	516
Journal	Journal of the National Cancer Institute
Volume	112
Issue number	5
Early online date	21 Aug 2019
DOIs	https://doi.org/10.1093/jnci/djz166
Publication status	Early online date - 21 Aug 2019

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Tilman Kuhn
- t.kuhnqub.acuk
- School of Biological Sciences - Lecturer
- Institute for Global Food Security
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Kühn, T., Stepien, M., López-Nogueroles, M., Machado, A. D., Sookthai, D., Johnson, T., Roca, M., Hüsing, A., Maldonado, S. G., Cross, A. J., Murphy, N., Freisling, H., Rinaldi, S., Scalbert, A., Fedirco, V., Severi, G., Boutron-Ruault, M.-C., Mancini, F. R., Sowah, S. A., ... Kaaks, R. (2019). Pre-diagnostic plasma bile acid levels and colon cancer risk: A prospective study. Journal of the National Cancer Institute, 112(5), 516. Advance online publication. https://doi.org/10.1093/jnci/djz166

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title = "Pre-diagnostic plasma bile acid levels and colon cancer risk: A prospective study",

abstract = "BACKGROUND: Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans.METHODS: Associations between pre-diagnostic plasma levels of 17 primary, secondary and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations.RESULTS: Positive associations were observed between colon cancer risk and plasma levels of 7 conjugated bile acid metabolites, i.e. primary bile acids glycocholic acid (ORQuartile 4 vs. Quartile 1=2.22,95 % confidence interval[CI]=1.52, 3.26), taurocholic acid (OR = 1.78, 95%CI=1.23, 2.58), glycochenodeoxycholic acid (OR = 1.68, 95%CI=1.13, 2.48), taurochenodeoxycholic acid (OR = 1.62, 95%CI=1.11-2.36), and glycohyocholic acid (OR = 1.65, 95%CI=1.13, 2.40) as well as the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95%CI=1.12, 2.54) and taurodeoxycholic acid (OR = 1.54, 95%CI=1.02, 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk.CONCLUSIONS: This prospective study showed that pre-diagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.",

author = "Tilman K{\"u}hn and Magdalena Stepien and Marina L{\'o}pez-Nogueroles and Machado, {Antje Damms} and Disorn Sookthai and Theron Johnson and Marta Roca and Anika H{\"u}sing and Maldonado, {Sandra Gonz{\'a}lez} and Cross, {Amanda J} and Neil Murphy and Heinz Freisling and Sabina Rinaldi and Augustin Scalbert and Veronika Fedirco and Gianluca Severi and Marie-Christine Boutron-Ruault and Mancini, {Francesca Romana} and Sowah, {Solomon A} and Heiner Boeing and Paula Jakszyn and Maria-Jose S{\'a}nchez and Susana Merino and Sandra Colorado-Yohar and Aurelio Barricarte and Khaw, {Kay Tee} and Schmidt, {Julie A} and Aurora Perez-Cornago and Antonia Trichopoulou and Anna Karakatsani and Paschalis Thriskos and Domenico Palli and Claudia Agnoli and Rosario Tumino and Carlotta Sacerdote and Salvatore Panico and Bas Bueno-de-Mesquita and {van Gils}, {Carla H} and Alicia Heath and Gunter, {Marc J} and Elio Riboli and Agust{\'i}n Lahoz and Mazda Jenab and Rudolf Kaaks",

year = "2019",

month = aug,

day = "21",

doi = "10.1093/jnci/djz166",

language = "English",

volume = "112",

pages = "516",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

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Kühn, T, Stepien, M, López-Nogueroles, M, Machado, AD, Sookthai, D, Johnson, T, Roca, M, Hüsing, A, Maldonado, SG, Cross, AJ, Murphy, N, Freisling, H, Rinaldi, S, Scalbert, A, Fedirco, V, Severi, G, Boutron-Ruault, M-C, Mancini, FR, Sowah, SA, Boeing, H, Jakszyn, P, Sánchez, M-J, Merino, S, Colorado-Yohar, S, Barricarte, A, Khaw, KT, Schmidt, JA, Perez-Cornago, A, Trichopoulou, A, Karakatsani, A, Thriskos, P, Palli, D, Agnoli, C, Tumino, R, Sacerdote, C, Panico, S, Bueno-de-Mesquita, B, van Gils, CH, Heath, A, Gunter, MJ, Riboli, E, Lahoz, A, Jenab, M & Kaaks, R 2019, 'Pre-diagnostic plasma bile acid levels and colon cancer risk: A prospective study', Journal of the National Cancer Institute, vol. 112, no. 5, pp. 516. https://doi.org/10.1093/jnci/djz166

TY - JOUR

T1 - Pre-diagnostic plasma bile acid levels and colon cancer risk: A prospective study

AU - Kühn, Tilman

AU - Stepien, Magdalena

AU - López-Nogueroles, Marina

AU - Machado, Antje Damms

AU - Sookthai, Disorn

AU - Johnson, Theron

AU - Roca, Marta

AU - Hüsing, Anika

AU - Maldonado, Sandra González

AU - Cross, Amanda J

AU - Murphy, Neil

AU - Freisling, Heinz

AU - Rinaldi, Sabina

AU - Scalbert, Augustin

AU - Fedirco, Veronika

AU - Severi, Gianluca

AU - Boutron-Ruault, Marie-Christine

AU - Mancini, Francesca Romana

AU - Sowah, Solomon A

AU - Boeing, Heiner

AU - Jakszyn, Paula

AU - Sánchez, Maria-Jose

AU - Merino, Susana

AU - Colorado-Yohar, Sandra

AU - Barricarte, Aurelio

AU - Khaw, Kay Tee

AU - Schmidt, Julie A

AU - Perez-Cornago, Aurora

AU - Trichopoulou, Antonia

AU - Karakatsani, Anna

AU - Thriskos, Paschalis

AU - Palli, Domenico

AU - Agnoli, Claudia

AU - Tumino, Rosario

AU - Sacerdote, Carlotta

AU - Panico, Salvatore

AU - Bueno-de-Mesquita, Bas

AU - van Gils, Carla H

AU - Heath, Alicia

AU - Gunter, Marc J

AU - Riboli, Elio

AU - Lahoz, Agustín

AU - Jenab, Mazda

AU - Kaaks, Rudolf

PY - 2019/8/21

Y1 - 2019/8/21

N2 - BACKGROUND: Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans.METHODS: Associations between pre-diagnostic plasma levels of 17 primary, secondary and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations.RESULTS: Positive associations were observed between colon cancer risk and plasma levels of 7 conjugated bile acid metabolites, i.e. primary bile acids glycocholic acid (ORQuartile 4 vs. Quartile 1=2.22,95 % confidence interval[CI]=1.52, 3.26), taurocholic acid (OR = 1.78, 95%CI=1.23, 2.58), glycochenodeoxycholic acid (OR = 1.68, 95%CI=1.13, 2.48), taurochenodeoxycholic acid (OR = 1.62, 95%CI=1.11-2.36), and glycohyocholic acid (OR = 1.65, 95%CI=1.13, 2.40) as well as the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95%CI=1.12, 2.54) and taurodeoxycholic acid (OR = 1.54, 95%CI=1.02, 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk.CONCLUSIONS: This prospective study showed that pre-diagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.

AB - BACKGROUND: Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans.METHODS: Associations between pre-diagnostic plasma levels of 17 primary, secondary and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations.RESULTS: Positive associations were observed between colon cancer risk and plasma levels of 7 conjugated bile acid metabolites, i.e. primary bile acids glycocholic acid (ORQuartile 4 vs. Quartile 1=2.22,95 % confidence interval[CI]=1.52, 3.26), taurocholic acid (OR = 1.78, 95%CI=1.23, 2.58), glycochenodeoxycholic acid (OR = 1.68, 95%CI=1.13, 2.48), taurochenodeoxycholic acid (OR = 1.62, 95%CI=1.11-2.36), and glycohyocholic acid (OR = 1.65, 95%CI=1.13, 2.40) as well as the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95%CI=1.12, 2.54) and taurodeoxycholic acid (OR = 1.54, 95%CI=1.02, 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk.CONCLUSIONS: This prospective study showed that pre-diagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.

U2 - 10.1093/jnci/djz166

DO - 10.1093/jnci/djz166

M3 - Article

C2 - 31435679

SN - 0027-8874

VL - 112

SP - 516

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 5

ER -

Pre-diagnostic plasma bile acid levels and colon cancer risk: A prospective study

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