Prospective association of liver function biomarkers with development of hepatobiliary cancers

M. Stepien; V. Fedirko; T. Duarte-Salles; P. Ferrari; H. Freisling; E. Trepo; A. Trichopoulou; C. Bamia; E. Weiderpass; A. Olsen; A. Tjonneland; K. Overvad; M. C. Boutron-Ruault; G. Fagherazzi; A. Racine; T. Kuhn; R. Kaaks; K. Aleksandrova; H. Boeing; P. Lagiou; V. Benetou; D. Trichopoulos; D. Palli; S. Grioni; R. Tumino; A. Naccarati; S. Panico; H. B. Bueno-de-Mesquita; P. H. Peeters; E. Lund; J. R. Quiros; O. C. Napoles; M. J. Sanchez; M. Dorronsoro; J. M. Huerta; E. Ardanaz; B. Ohlsson; K. Sjoberg; M. Werner; H. Nystrom; K. T. Khaw; T. J. Key; M. Gunter; A. Cross; E. Riboli; I. Romieu; M. Jenab

doi:10.1016/j.canep.2016.01.002

Prospective association of liver function biomarkers with development of hepatobiliary cancers

M. Stepien, V. Fedirko, T. Duarte-Salles, P. Ferrari, H. Freisling, E. Trepo, A. Trichopoulou, C. Bamia, E. Weiderpass, A. Olsen, A. Tjonneland, K. Overvad, M. C. Boutron-Ruault, G. Fagherazzi, A. Racine, T. Kuhn, R. Kaaks, K. Aleksandrova, H. Boeing, P. LagiouV. Benetou, D. Trichopoulos, D. Palli, S. Grioni, R. Tumino, A. Naccarati, S. Panico, H. B. Bueno-de-Mesquita, P. H. Peeters, E. Lund, J. R. Quiros, O. C. Napoles, M. J. Sanchez, M. Dorronsoro, J. M. Huerta, E. Ardanaz, B. Ohlsson, K. Sjoberg, M. Werner, H. Nystrom, K. T. Khaw, T. J. Key, M. Gunter, A. Cross, E. Riboli, I. Romieu, M. Jenab

School of Biological Sciences

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

47 Citations (Scopus)

Abstract

Introduction

Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers.

Methods

A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI).

Results

In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT) = 4.23, 95%CI:2.72–6.59; OR(ALP) = 3.43, 95%CI:2.31–5.10;OR(AST) = 3.00, 95%CI:2.04-4.42; OR(ALT) = 2.69, 95%CI:1.89–3.84; OR(Bilirubin) = 2.25, 95%CI:1.58–3.20). Each liver enzyme (OR(GGT) = 4.98; 95%CI:1.75–14.17; OR(AST) = 3.10, 95%CI:1.04–9.30; OR(ALT) = 2.86, 95%CI:1.26–6.48, OR(ALP) = 2.31, 95%CI:1.10–4.86) but not bilirubin (OR(Bilirubin) = 1.46,95%CI:0.85–2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP) = 1.59, 95%CI:1.20–2.09).

Conclusion

This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.

Original language	Undefined/Unknown
Pages (from-to)	179-87
Number of pages	9
Journal	Cancer Epidemiology
Volume	40
Early online date	11 Jan 2016
DOIs	https://doi.org/10.1016/j.canep.2016.01.002
Publication status	Published - Feb 2016

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Cite this

Stepien, M., Fedirko, V., Duarte-Salles, T., Ferrari, P., Freisling, H., Trepo, E., Trichopoulou, A., Bamia, C., Weiderpass, E., Olsen, A., Tjonneland, A., Overvad, K., Boutron-Ruault, M. C., Fagherazzi, G., Racine, A., Kuhn, T., Kaaks, R., Aleksandrova, K., Boeing, H., ... Jenab, M. (2016). Prospective association of liver function biomarkers with development of hepatobiliary cancers. Cancer Epidemiology, 40, 179-87. https://doi.org/10.1016/j.canep.2016.01.002

@article{3ad4e645c7494917a5c5514a8b5a7263,

title = "Prospective association of liver function biomarkers with development of hepatobiliary cancers",

abstract = "IntroductionSerum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers.MethodsA nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI).ResultsIn multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT) = 4.23, 95%CI:2.72–6.59; OR(ALP) = 3.43, 95%CI:2.31–5.10;OR(AST) = 3.00, 95%CI:2.04-4.42; OR(ALT) = 2.69, 95%CI:1.89–3.84; OR(Bilirubin) = 2.25, 95%CI:1.58–3.20). Each liver enzyme (OR(GGT) = 4.98; 95%CI:1.75–14.17; OR(AST) = 3.10, 95%CI:1.04–9.30; OR(ALT) = 2.86, 95%CI:1.26–6.48, OR(ALP) = 2.31, 95%CI:1.10–4.86) but not bilirubin (OR(Bilirubin) = 1.46,95%CI:0.85–2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP) = 1.59, 95%CI:1.20–2.09).ConclusionThis study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.",

author = "M. Stepien and V. Fedirko and T. Duarte-Salles and P. Ferrari and H. Freisling and E. Trepo and A. Trichopoulou and C. Bamia and E. Weiderpass and A. Olsen and A. Tjonneland and K. Overvad and Boutron-Ruault, {M. C.} and G. Fagherazzi and A. Racine and T. Kuhn and R. Kaaks and K. Aleksandrova and H. Boeing and P. Lagiou and V. Benetou and D. Trichopoulos and D. Palli and S. Grioni and R. Tumino and A. Naccarati and S. Panico and Bueno-de-Mesquita, {H. B.} and Peeters, {P. H.} and E. Lund and Quiros, {J. R.} and Napoles, {O. C.} and Sanchez, {M. J.} and M. Dorronsoro and Huerta, {J. M.} and E. Ardanaz and B. Ohlsson and K. Sjoberg and M. Werner and H. Nystrom and Khaw, {K. T.} and Key, {T. J.} and M. Gunter and A. Cross and E. Riboli and I. Romieu and M. Jenab",

year = "2016",

month = feb,

doi = "10.1016/j.canep.2016.01.002",

language = "Undefined/Unknown",

volume = "40",

pages = "179--87",

journal = "Cancer Epidemiology",

issn = "1877-7821",

publisher = "Elsevier Ltd",

}

Stepien, M, Fedirko, V, Duarte-Salles, T, Ferrari, P, Freisling, H, Trepo, E, Trichopoulou, A, Bamia, C, Weiderpass, E, Olsen, A, Tjonneland, A, Overvad, K, Boutron-Ruault, MC, Fagherazzi, G, Racine, A, Kuhn, T, Kaaks, R, Aleksandrova, K, Boeing, H, Lagiou, P, Benetou, V, Trichopoulos, D, Palli, D, Grioni, S, Tumino, R, Naccarati, A, Panico, S, Bueno-de-Mesquita, HB, Peeters, PH, Lund, E, Quiros, JR, Napoles, OC, Sanchez, MJ, Dorronsoro, M, Huerta, JM, Ardanaz, E, Ohlsson, B, Sjoberg, K, Werner, M, Nystrom, H, Khaw, KT, Key, TJ, Gunter, M, Cross, A, Riboli, E, Romieu, I & Jenab, M 2016, 'Prospective association of liver function biomarkers with development of hepatobiliary cancers', Cancer Epidemiology, vol. 40, pp. 179-87. https://doi.org/10.1016/j.canep.2016.01.002

TY - JOUR

T1 - Prospective association of liver function biomarkers with development of hepatobiliary cancers

AU - Stepien, M.

AU - Fedirko, V.

AU - Duarte-Salles, T.

AU - Ferrari, P.

AU - Freisling, H.

AU - Trepo, E.

AU - Trichopoulou, A.

AU - Bamia, C.

AU - Weiderpass, E.

AU - Olsen, A.

AU - Tjonneland, A.

AU - Overvad, K.

AU - Boutron-Ruault, M. C.

AU - Fagherazzi, G.

AU - Racine, A.

AU - Kuhn, T.

AU - Kaaks, R.

AU - Aleksandrova, K.

AU - Boeing, H.

AU - Lagiou, P.

AU - Benetou, V.

AU - Trichopoulos, D.

AU - Palli, D.

AU - Grioni, S.

AU - Tumino, R.

AU - Naccarati, A.

AU - Panico, S.

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

AU - Peeters, P. H.

AU - Lund, E.

AU - Quiros, J. R.

AU - Napoles, O. C.

AU - Sanchez, M. J.

AU - Dorronsoro, M.

AU - Huerta, J. M.

AU - Ardanaz, E.

AU - Ohlsson, B.

AU - Sjoberg, K.

AU - Werner, M.

AU - Nystrom, H.

AU - Khaw, K. T.

AU - Key, T. J.

AU - Gunter, M.

AU - Cross, A.

AU - Riboli, E.

AU - Romieu, I.

AU - Jenab, M.

PY - 2016/2

Y1 - 2016/2

N2 - IntroductionSerum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers.MethodsA nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI).ResultsIn multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT) = 4.23, 95%CI:2.72–6.59; OR(ALP) = 3.43, 95%CI:2.31–5.10;OR(AST) = 3.00, 95%CI:2.04-4.42; OR(ALT) = 2.69, 95%CI:1.89–3.84; OR(Bilirubin) = 2.25, 95%CI:1.58–3.20). Each liver enzyme (OR(GGT) = 4.98; 95%CI:1.75–14.17; OR(AST) = 3.10, 95%CI:1.04–9.30; OR(ALT) = 2.86, 95%CI:1.26–6.48, OR(ALP) = 2.31, 95%CI:1.10–4.86) but not bilirubin (OR(Bilirubin) = 1.46,95%CI:0.85–2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP) = 1.59, 95%CI:1.20–2.09).ConclusionThis study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.

AB - IntroductionSerum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers.MethodsA nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI).ResultsIn multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT) = 4.23, 95%CI:2.72–6.59; OR(ALP) = 3.43, 95%CI:2.31–5.10;OR(AST) = 3.00, 95%CI:2.04-4.42; OR(ALT) = 2.69, 95%CI:1.89–3.84; OR(Bilirubin) = 2.25, 95%CI:1.58–3.20). Each liver enzyme (OR(GGT) = 4.98; 95%CI:1.75–14.17; OR(AST) = 3.10, 95%CI:1.04–9.30; OR(ALT) = 2.86, 95%CI:1.26–6.48, OR(ALP) = 2.31, 95%CI:1.10–4.86) but not bilirubin (OR(Bilirubin) = 1.46,95%CI:0.85–2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP) = 1.59, 95%CI:1.20–2.09).ConclusionThis study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.

U2 - 10.1016/j.canep.2016.01.002

DO - 10.1016/j.canep.2016.01.002

M3 - Article

SN - 1877-7821

VL - 40

SP - 179

EP - 187

JO - Cancer Epidemiology

JF - Cancer Epidemiology

ER -