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 Tjønneland, Anja Olsen, Kim Overvad, Marie Christine Boutron-Ruault, Françoise Clavel-Chapelon, Marina Kvaskoff, Tilman Kühn, 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, María José Sánchez, Eva Ardanaz, Pilar Amiano, Carmen Navarro, J. Ramón Quirós, Mårten Werner, Malin Sund, Björn Lindkvist, Johan Malm, Ruth C. Travis, Kay Tee Khaw, Magdalena Stepien, Augustin Scalbert, Isabelle Romieu, Pagona Lagiou, Elio Riboli, Mazda Jenab

Research output: Contribution to journalArticle

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; Ptrend=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.

Original languageEnglish
Pages (from-to)1222-1230
Number of pages9
JournalHepatology
Volume60
Issue number4
DOIs
Publication statusPublished - Oct 1 2014

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Vitamin D
Case-Control Studies
Hepatocellular Carcinoma
Population
Serum
Confidence Intervals
Neoplasms
Liver
Body Size
Risk Reduction Behavior
Tandem Mass Spectrometry
Developed Countries
Hepatitis B virus
Liquid Chromatography
Hepacivirus
Fasting
Public Health
Biomarkers
Logistic Models
Smoking

ASJC Scopus subject areas

  • Hepatology

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Fedirko, V., Duarte-Salles, T., Bamia, C., Trichopoulou, A., Aleksandrova, K., Trichopoulos, D., ... 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

Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations : A nested case-control study. / Fedirko, Veronika; Duarte-Salles, Talita; Bamia, Christina; Trichopoulou, Antonia; Aleksandrova, Krasimira; Trichopoulos, Dimitrios; Trepo, Elisabeth; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie Christine; Clavel-Chapelon, Françoise; Kvaskoff, Marina; Kühn, Tilman; Lukanova, Annie; Boeing, Heiner; Buijsse, Brian; Klinaki, Eleni; Tsimakidi, Chrysanthi; Naccarati, Alessio; Tagliabue, Giovanna; Panico, Salvatore; Tumino, Rosario; Palli, Domenico; Bueno-de-Mesquita, H. Bas; Siersema, Peter D.; Peters, Petra H.; Lund, Eiliv; Brustad, Magritt; Olsen, Karina Standahl; Weiderpass, Elisabete; Zamora-Ros, Raul; Sánchez, María José; Ardanaz, Eva; Amiano, Pilar; Navarro, Carmen; Quirós, J. Ramón; Werner, Mårten; Sund, Malin; Lindkvist, Björn; Malm, Johan; Travis, Ruth C.; Khaw, Kay Tee; Stepien, Magdalena; Scalbert, Augustin; Romieu, Isabelle; Lagiou, Pagona; Riboli, Elio; Jenab, Mazda.

In: Hepatology, Vol. 60, No. 4, 01.10.2014, p. 1222-1230.

Research output: Contribution to journalArticle

Fedirko, V, Duarte-Salles, T, Bamia, C, Trichopoulou, A, Aleksandrova, K, Trichopoulos, D, Trepo, E, Tjønneland, A, Olsen, A, Overvad, K, Boutron-Ruault, MC, Clavel-Chapelon, F, Kvaskoff, M, Kühn, 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, Sánchez, MJ, Ardanaz, E, Amiano, P, Navarro, C, Quirós, JR, Werner, M, Sund, M, Lindkvist, B, Malm, J, Travis, RC, Khaw, KT, 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
Fedirko V, Duarte-Salles T, Bamia C, Trichopoulou A, Aleksandrova K, Trichopoulos D et al. Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: A nested case-control study. Hepatology. 2014 Oct 1;60(4):1222-1230. https://doi.org/10.1002/hep.27079
Fedirko, Veronika ; Duarte-Salles, Talita ; Bamia, Christina ; Trichopoulou, Antonia ; Aleksandrova, Krasimira ; Trichopoulos, Dimitrios ; Trepo, Elisabeth ; Tjønneland, Anne ; Olsen, Anja ; Overvad, Kim ; Boutron-Ruault, Marie Christine ; Clavel-Chapelon, Françoise ; Kvaskoff, Marina ; Kühn, Tilman ; Lukanova, Annie ; Boeing, Heiner ; Buijsse, Brian ; Klinaki, Eleni ; Tsimakidi, Chrysanthi ; Naccarati, Alessio ; Tagliabue, Giovanna ; Panico, Salvatore ; Tumino, Rosario ; Palli, Domenico ; Bueno-de-Mesquita, H. Bas ; Siersema, Peter D. ; Peters, Petra H. ; Lund, Eiliv ; Brustad, Magritt ; Olsen, Karina Standahl ; Weiderpass, Elisabete ; Zamora-Ros, Raul ; Sánchez, María José ; Ardanaz, Eva ; Amiano, Pilar ; Navarro, Carmen ; Quirós, J. Ramón ; Werner, Mårten ; Sund, Malin ; Lindkvist, Björn ; Malm, Johan ; Travis, Ruth C. ; Khaw, Kay Tee ; Stepien, Magdalena ; Scalbert, Augustin ; Romieu, Isabelle ; Lagiou, Pagona ; Riboli, Elio ; Jenab, Mazda. / Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations : A nested case-control study. In: Hepatology. 2014 ; Vol. 60, No. 4. pp. 1222-1230.
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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; Ptrend=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.",
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T1 - Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations

T2 - 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 - Tjønneland, Anne

AU - Olsen, Anja

AU - Overvad, Kim

AU - Boutron-Ruault, Marie Christine

AU - Clavel-Chapelon, Françoise

AU - Kvaskoff, Marina

AU - Kühn, 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 - Sánchez, María José

AU - Ardanaz, Eva

AU - Amiano, Pilar

AU - Navarro, Carmen

AU - Quirós, J. Ramón

AU - Werner, Mårten

AU - Sund, Malin

AU - Lindkvist, Björn

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 - 2014/10/1

Y1 - 2014/10/1

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; Ptrend=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.

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; Ptrend=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.

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