Prediagnostic Circulating Vitamin D Levels and Risk of Hepatocellular Carcinoma in European Populations: A Nested Case-Control Study

Veronika Fedirko; Talita Duarte-Salles; Christina Bamia; Antonia Trichopoulou; Krasimira Aleksandrova; Dimitrios Trichopoulos; Elisabeth Trepo; Anne Tjonneland; Anja Olsen; Kim Overvad; Marie-Christine Boutron-Ruault; Francoise Clavel-Chapelon; Marina Kvaskoff; Tilman Kuehn; Annie Lukanova; Heiner Boeing; Brian Buijsse; Eleni Klinaki; Chrysanthi Tsimakidi; Alessio Naccarati; Giovanna Tagliabue; Salvatore Panico; Rosario Tumino; Domenico Palli; H. Bas Bueno-de-Mesquita; Peter D. Siersema; Petra H. Peters; Eiliv Lund; Magritt Brustad; Karina Standahl Olsen; Elisabete Weiderpass; Raul Zamora-Ros; Maria-Jose Sanchez; Eva Ardanaz; Pilar Amiano; Carmen Navarro; J. Ramon Quiros; Marten Werner; Malin Sund; Bjorn Lindkvist; Johan Malm; Ruth C. Travis; Kay-Tee Khaw; Magdalena Stepien; Augustin Scalbert; Isabelle Romieu; Pagona Lagiou; Elio Riboli; Mazda Jenab

doi:10.1002/hep.27079

Prediagnostic Circulating Vitamin D Levels and Risk of Hepatocellular Carcinoma in European Populations: A Nested Case-Control Study

Veronika Fedirko, Talita Duarte-Salles, Christina Bamia, Antonia Trichopoulou, Krasimira Aleksandrova, Dimitrios Trichopoulos, Elisabeth Trepo, Anne Tjonneland, Anja Olsen, Kim Overvad, Marie-Christine Boutron-Ruault, Francoise Clavel-Chapelon, Marina Kvaskoff, Tilman Kuehn, Annie Lukanova, Heiner Boeing, Brian Buijsse, Eleni Klinaki, Chrysanthi Tsimakidi, Alessio NaccaratiGiovanna Tagliabue, Salvatore Panico, Rosario Tumino, Domenico Palli, H. Bas Bueno-de-Mesquita, Peter D. Siersema, Petra H. Peters, Eiliv Lund, Magritt Brustad, Karina Standahl Olsen, Elisabete Weiderpass, Raul Zamora-Ros, Maria-Jose Sanchez, Eva Ardanaz, Pilar Amiano, Carmen Navarro, J. Ramon Quiros, Marten Werner, Malin Sund, Bjorn Lindkvist, Johan Malm, Ruth C. Travis, Kay-Tee Khaw, Magdalena Stepien, Augustin Scalbert, Isabelle Romieu, Pagona Lagiou, Elio Riboli, Mazda Jenab

Clinical Chemistry, Malmö

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Abstract

The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between prediagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and the risk of HCC in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n=138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRRs) of HCC associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of prediagnostic 25(OH)D were calculated using conditional logistic regression. Higher 25(OH)D levels were associated with a 49% reduction in the risk of HCC (highest versus lowest tertile: multivariable IRR=0.51, 95% confidence interval [CI], 0.26 to 0.99; P-trend=0.04; per 10 nmol/L increase: IRR=0.80, 95% CI, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of preexisting liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. Conclusion: In this prospective study on western European populations, serum levels of 25(OH)D were inversely associated with the risk of HCC. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required. (Hepatology 2014;60:1222-1230)

Original language	English
Pages (from-to)	1222-1230
Journal	Hepatology
Volume	60
Issue number	4
DOIs	https://doi.org/10.1002/hep.27079
Publication status	Published - 2014

Subject classification (UKÄ)

Gastroenterology and Hepatology

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10.1002/hep.27079

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Fedirko, V., Duarte-Salles, T., Bamia, C., Trichopoulou, A., Aleksandrova, K., Trichopoulos, D., Trepo, E., Tjonneland, A., Olsen, A., Overvad, K., Boutron-Ruault, M-C., Clavel-Chapelon, F., Kvaskoff, M., Kuehn, T., Lukanova, A., Boeing, H., Buijsse, B., Klinaki, E., Tsimakidi, C., ... Jenab, M. (2014). Prediagnostic Circulating Vitamin D Levels and Risk of Hepatocellular Carcinoma in European Populations: A Nested Case-Control Study. Hepatology, 60(4), 1222-1230. https://doi.org/10.1002/hep.27079

@article{c3df05e29d4a425ab868261985678898,

title = "Prediagnostic Circulating Vitamin D Levels and Risk of Hepatocellular Carcinoma in European Populations: A Nested Case-Control Study",

abstract = "The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between prediagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and the risk of HCC in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n=138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRRs) of HCC associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of prediagnostic 25(OH)D were calculated using conditional logistic regression. Higher 25(OH)D levels were associated with a 49% reduction in the risk of HCC (highest versus lowest tertile: multivariable IRR=0.51, 95% confidence interval [CI], 0.26 to 0.99; P-trend=0.04; per 10 nmol/L increase: IRR=0.80, 95% CI, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of preexisting liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. Conclusion: In this prospective study on western European populations, serum levels of 25(OH)D were inversely associated with the risk of HCC. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required. (Hepatology 2014;60:1222-1230)",

author = "Veronika Fedirko and Talita Duarte-Salles and Christina Bamia and Antonia Trichopoulou and Krasimira Aleksandrova and Dimitrios Trichopoulos and Elisabeth Trepo and Anne Tjonneland and Anja Olsen and Kim Overvad and Marie-Christine Boutron-Ruault and Francoise Clavel-Chapelon and Marina Kvaskoff and Tilman Kuehn and Annie Lukanova and Heiner Boeing and Brian Buijsse and Eleni Klinaki and Chrysanthi Tsimakidi and Alessio Naccarati and Giovanna Tagliabue and Salvatore Panico and Rosario Tumino and Domenico Palli and Bueno-de-Mesquita, {H. Bas} and Siersema, {Peter D.} and Peters, {Petra H.} and Eiliv Lund and Magritt Brustad and Olsen, {Karina Standahl} and Elisabete Weiderpass and Raul Zamora-Ros and Maria-Jose Sanchez and Eva Ardanaz and Pilar Amiano and Carmen Navarro and {Ramon Quiros}, J. and Marten Werner and Malin Sund and Bjorn Lindkvist and Johan Malm and Travis, {Ruth C.} and Kay-Tee Khaw and Magdalena Stepien and Augustin Scalbert and Isabelle Romieu and Pagona Lagiou and Elio Riboli and Mazda Jenab",

year = "2014",

doi = "10.1002/hep.27079",

language = "English",

volume = "60",

pages = "1222--1230",

journal = "Hepatology",

issn = "1527-3350",

publisher = "John Wiley & Sons Inc.",

number = "4",

}

Fedirko, V, Duarte-Salles, T, Bamia, C, Trichopoulou, A, Aleksandrova, K, Trichopoulos, D, Trepo, E, Tjonneland, A, Olsen, A, Overvad, K, Boutron-Ruault, M-C, Clavel-Chapelon, F, Kvaskoff, M, Kuehn, T, Lukanova, A, Boeing, H, Buijsse, B, Klinaki, E, Tsimakidi, C, Naccarati, A, Tagliabue, G, Panico, S, Tumino, R, Palli, D, Bueno-de-Mesquita, HB, Siersema, PD, Peters, PH, Lund, E, Brustad, M, Olsen, KS, Weiderpass, E, Zamora-Ros, R, Sanchez, M-J, Ardanaz, E, Amiano, P, Navarro, C, Ramon Quiros, J, Werner, M, Sund, M, Lindkvist, B, Malm, J, Travis, RC, Khaw, K-T, Stepien, M, Scalbert, A, Romieu, I, Lagiou, P, Riboli, E & Jenab, M 2014, 'Prediagnostic Circulating Vitamin D Levels and Risk of Hepatocellular Carcinoma in European Populations: A Nested Case-Control Study', Hepatology, vol. 60, no. 4, pp. 1222-1230. https://doi.org/10.1002/hep.27079

TY - JOUR

T1 - Prediagnostic Circulating Vitamin D Levels and Risk of Hepatocellular Carcinoma in European Populations: A Nested Case-Control Study

AU - Fedirko, Veronika

AU - Duarte-Salles, Talita

AU - Bamia, Christina

AU - Trichopoulou, Antonia

AU - Aleksandrova, Krasimira

AU - Trichopoulos, Dimitrios

AU - Trepo, Elisabeth

AU - Tjonneland, Anne

AU - Olsen, Anja

AU - Overvad, Kim

AU - Boutron-Ruault, Marie-Christine

AU - Clavel-Chapelon, Francoise

AU - Kvaskoff, Marina

AU - Kuehn, Tilman

AU - Lukanova, Annie

AU - Boeing, Heiner

AU - Buijsse, Brian

AU - Klinaki, Eleni

AU - Tsimakidi, Chrysanthi

AU - Naccarati, Alessio

AU - Tagliabue, Giovanna

AU - Panico, Salvatore

AU - Tumino, Rosario

AU - Palli, Domenico

AU - Bueno-de-Mesquita, H. Bas

AU - Siersema, Peter D.

AU - Peters, Petra H.

AU - Lund, Eiliv

AU - Brustad, Magritt

AU - Olsen, Karina Standahl

AU - Weiderpass, Elisabete

AU - Zamora-Ros, Raul

AU - Sanchez, Maria-Jose

AU - Ardanaz, Eva

AU - Amiano, Pilar

AU - Navarro, Carmen

AU - Ramon Quiros, J.

AU - Werner, Marten

AU - Sund, Malin

AU - Lindkvist, Bjorn

AU - Malm, Johan

AU - Travis, Ruth C.

AU - Khaw, Kay-Tee

AU - Stepien, Magdalena

AU - Scalbert, Augustin

AU - Romieu, Isabelle

AU - Lagiou, Pagona

AU - Riboli, Elio

AU - Jenab, Mazda

PY - 2014

Y1 - 2014

N2 - The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between prediagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and the risk of HCC in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n=138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRRs) of HCC associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of prediagnostic 25(OH)D were calculated using conditional logistic regression. Higher 25(OH)D levels were associated with a 49% reduction in the risk of HCC (highest versus lowest tertile: multivariable IRR=0.51, 95% confidence interval [CI], 0.26 to 0.99; P-trend=0.04; per 10 nmol/L increase: IRR=0.80, 95% CI, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of preexisting liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. Conclusion: In this prospective study on western European populations, serum levels of 25(OH)D were inversely associated with the risk of HCC. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required. (Hepatology 2014;60:1222-1230)

AB - The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between prediagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and the risk of HCC in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n=138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRRs) of HCC associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of prediagnostic 25(OH)D were calculated using conditional logistic regression. Higher 25(OH)D levels were associated with a 49% reduction in the risk of HCC (highest versus lowest tertile: multivariable IRR=0.51, 95% confidence interval [CI], 0.26 to 0.99; P-trend=0.04; per 10 nmol/L increase: IRR=0.80, 95% CI, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of preexisting liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. Conclusion: In this prospective study on western European populations, serum levels of 25(OH)D were inversely associated with the risk of HCC. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required. (Hepatology 2014;60:1222-1230)

U2 - 10.1002/hep.27079

DO - 10.1002/hep.27079

M3 - Article

C2 - 24644045

VL - 60

SP - 1222

EP - 1230

JO - Hepatology

JF - Hepatology

SN - 1527-3350

IS - 4

ER -

Prediagnostic Circulating Vitamin D Levels and Risk of Hepatocellular Carcinoma in European Populations: A Nested Case-Control Study

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