Body Mass Index, Diabetes and Intrahepatic Cholangiocarcinoma Risk: The Liver Cancer Pooling Project and Meta-analysis

Jessica L. Petrick, Jake E. Thistle, Anne Zeleniuch-Jacquotte, Xuehong Zhang, Jean Wactawski-Wende, Alison L. Van Dyke, Meir J. Stampfer, Rashmi Sinha, Howard D. Sesso, Catherine Schairer, Lynn Rosenberg, Thomas E. Rohan, Kim Robien, Mark P. Purdue, Jenny N. Poynter, Julie R. Palmer, Christina C. Newton, Martha S. Linet, Linda M. Liao, I. Min LeeJill Koshiol, Cari M. Kitahara, Jonathan N. Hofmann, Barry I. Graubard, Edward Giovannucci, J. Michael Gaziano, Susan M. Gapstur, Neal D. Freedman, Dawn Q. Chong, Andrew T. Chan, Julie E. Buring, Laura E. Beane Freeman, Peter T. Campbell, Katherine A. McGlynn

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective: Obesity and diabetes are associated with an increased liver cancer risk. However, most studies have examined all primary liver cancers or hepatocellular carcinoma, with few studies evaluating intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Thus, we examined the association between obesity and diabetes and ICC risk in a pooled analysis and conducted a systematic review/meta-analysis of the literature. Design: For the pooled analysis, we utilized the Liver Cancer Pooling Project, a consortium of 13 US-based, prospective cohort studies with data from 1,541,143 individuals (ICC cases n = 414). In our systematic review, we identified 14 additional studies. We then conducted a meta-analysis, combining the results from LCPP with results from the 5 prospective studies identified through September 2017. Results: In the LCPP, obesity and diabetes were associated with a 62% [Hazard Ratio (HR) = 1.62, 95% Confidence Interval (CI): 1.24–2.12] and an 81% (HR = 1.81, 95% CI: 1.33–2.46) increased ICC risk, respectively. In the meta-analysis of prospectively ascertained cohorts and nested case-control studies, obesity was associated with a 49% increased ICC risk [Relative Risk (RR) = 1.49, 95% CI: 1.32–1.70; n = 4 studies; I2 = 0%]. Diabetes was associated with a 53% increased ICC risk (RR = 1.53, 95% CI: 1.31–1.78; n = 6 studies). While we noted heterogeneity between studies (I2 = 67%) for diabetes, results were consistent in subgroup analyses. Results from hospital-based case–control studies (n = 9) were mostly consistent, but these studies are potentially subject to reverse causation. Conclusions: These findings suggest that obesity and diabetes are associated with increased ICC risk, highlighting similar etiologies of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. However, additional prospective studies are needed to verify these associations.

Original languageEnglish (US)
Pages (from-to)1494-1505
Number of pages12
JournalAmerican Journal of Gastroenterology
Volume113
Issue number10
DOIs
StatePublished - Oct 1 2018

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Cholangiocarcinoma
Liver Neoplasms
Meta-Analysis
Body Mass Index
Obesity
Confidence Intervals
Prospective Studies
Hepatocellular Carcinoma
Causality
Case-Control Studies
Cohort Studies

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Petrick, J. L., Thistle, J. E., Zeleniuch-Jacquotte, A., Zhang, X., Wactawski-Wende, J., Van Dyke, A. L., ... McGlynn, K. A. (2018). Body Mass Index, Diabetes and Intrahepatic Cholangiocarcinoma Risk: The Liver Cancer Pooling Project and Meta-analysis. American Journal of Gastroenterology, 113(10), 1494-1505. https://doi.org/10.1038/s41395-018-0207-4

Body Mass Index, Diabetes and Intrahepatic Cholangiocarcinoma Risk : The Liver Cancer Pooling Project and Meta-analysis. / Petrick, Jessica L.; Thistle, Jake E.; Zeleniuch-Jacquotte, Anne; Zhang, Xuehong; Wactawski-Wende, Jean; Van Dyke, Alison L.; Stampfer, Meir J.; Sinha, Rashmi; Sesso, Howard D.; Schairer, Catherine; Rosenberg, Lynn; Rohan, Thomas E.; Robien, Kim; Purdue, Mark P.; Poynter, Jenny N.; Palmer, Julie R.; Newton, Christina C.; Linet, Martha S.; Liao, Linda M.; Lee, I. Min; Koshiol, Jill; Kitahara, Cari M.; Hofmann, Jonathan N.; Graubard, Barry I.; Giovannucci, Edward; Gaziano, J. Michael; Gapstur, Susan M.; Freedman, Neal D.; Chong, Dawn Q.; Chan, Andrew T.; Buring, Julie E.; Beane Freeman, Laura E.; Campbell, Peter T.; McGlynn, Katherine A.

In: American Journal of Gastroenterology, Vol. 113, No. 10, 01.10.2018, p. 1494-1505.

Research output: Contribution to journalArticle

Petrick, JL, Thistle, JE, Zeleniuch-Jacquotte, A, Zhang, X, Wactawski-Wende, J, Van Dyke, AL, Stampfer, MJ, Sinha, R, Sesso, HD, Schairer, C, Rosenberg, L, Rohan, TE, Robien, K, Purdue, MP, Poynter, JN, Palmer, JR, Newton, CC, Linet, MS, Liao, LM, Lee, IM, Koshiol, J, Kitahara, CM, Hofmann, JN, Graubard, BI, Giovannucci, E, Gaziano, JM, Gapstur, SM, Freedman, ND, Chong, DQ, Chan, AT, Buring, JE, Beane Freeman, LE, Campbell, PT & McGlynn, KA 2018, 'Body Mass Index, Diabetes and Intrahepatic Cholangiocarcinoma Risk: The Liver Cancer Pooling Project and Meta-analysis', American Journal of Gastroenterology, vol. 113, no. 10, pp. 1494-1505. https://doi.org/10.1038/s41395-018-0207-4
Petrick, Jessica L. ; Thistle, Jake E. ; Zeleniuch-Jacquotte, Anne ; Zhang, Xuehong ; Wactawski-Wende, Jean ; Van Dyke, Alison L. ; Stampfer, Meir J. ; Sinha, Rashmi ; Sesso, Howard D. ; Schairer, Catherine ; Rosenberg, Lynn ; Rohan, Thomas E. ; Robien, Kim ; Purdue, Mark P. ; Poynter, Jenny N. ; Palmer, Julie R. ; Newton, Christina C. ; Linet, Martha S. ; Liao, Linda M. ; Lee, I. Min ; Koshiol, Jill ; Kitahara, Cari M. ; Hofmann, Jonathan N. ; Graubard, Barry I. ; Giovannucci, Edward ; Gaziano, J. Michael ; Gapstur, Susan M. ; Freedman, Neal D. ; Chong, Dawn Q. ; Chan, Andrew T. ; Buring, Julie E. ; Beane Freeman, Laura E. ; Campbell, Peter T. ; McGlynn, Katherine A. / Body Mass Index, Diabetes and Intrahepatic Cholangiocarcinoma Risk : The Liver Cancer Pooling Project and Meta-analysis. In: American Journal of Gastroenterology. 2018 ; Vol. 113, No. 10. pp. 1494-1505.
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abstract = "Objective: Obesity and diabetes are associated with an increased liver cancer risk. However, most studies have examined all primary liver cancers or hepatocellular carcinoma, with few studies evaluating intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Thus, we examined the association between obesity and diabetes and ICC risk in a pooled analysis and conducted a systematic review/meta-analysis of the literature. Design: For the pooled analysis, we utilized the Liver Cancer Pooling Project, a consortium of 13 US-based, prospective cohort studies with data from 1,541,143 individuals (ICC cases n = 414). In our systematic review, we identified 14 additional studies. We then conducted a meta-analysis, combining the results from LCPP with results from the 5 prospective studies identified through September 2017. Results: In the LCPP, obesity and diabetes were associated with a 62{\%} [Hazard Ratio (HR) = 1.62, 95{\%} Confidence Interval (CI): 1.24–2.12] and an 81{\%} (HR = 1.81, 95{\%} CI: 1.33–2.46) increased ICC risk, respectively. In the meta-analysis of prospectively ascertained cohorts and nested case-control studies, obesity was associated with a 49{\%} increased ICC risk [Relative Risk (RR) = 1.49, 95{\%} CI: 1.32–1.70; n = 4 studies; I2 = 0{\%}]. Diabetes was associated with a 53{\%} increased ICC risk (RR = 1.53, 95{\%} CI: 1.31–1.78; n = 6 studies). While we noted heterogeneity between studies (I2 = 67{\%}) for diabetes, results were consistent in subgroup analyses. Results from hospital-based case–control studies (n = 9) were mostly consistent, but these studies are potentially subject to reverse causation. Conclusions: These findings suggest that obesity and diabetes are associated with increased ICC risk, highlighting similar etiologies of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. However, additional prospective studies are needed to verify these associations.",
author = "Petrick, {Jessica L.} and Thistle, {Jake E.} and Anne Zeleniuch-Jacquotte and Xuehong Zhang and Jean Wactawski-Wende and {Van Dyke}, {Alison L.} and Stampfer, {Meir J.} and Rashmi Sinha and Sesso, {Howard D.} and Catherine Schairer and Lynn Rosenberg and Rohan, {Thomas E.} and Kim Robien and Purdue, {Mark P.} and Poynter, {Jenny N.} and Palmer, {Julie R.} and Newton, {Christina C.} and Linet, {Martha S.} and Liao, {Linda M.} and Lee, {I. Min} and Jill Koshiol and Kitahara, {Cari M.} and Hofmann, {Jonathan N.} and Graubard, {Barry I.} and Edward Giovannucci and Gaziano, {J. Michael} and Gapstur, {Susan M.} and Freedman, {Neal D.} and Chong, {Dawn Q.} and Chan, {Andrew T.} and Buring, {Julie E.} and {Beane Freeman}, {Laura E.} and Campbell, {Peter T.} and McGlynn, {Katherine A.}",
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TY - JOUR

T1 - Body Mass Index, Diabetes and Intrahepatic Cholangiocarcinoma Risk

T2 - The Liver Cancer Pooling Project and Meta-analysis

AU - Petrick, Jessica L.

AU - Thistle, Jake E.

AU - Zeleniuch-Jacquotte, Anne

AU - Zhang, Xuehong

AU - Wactawski-Wende, Jean

AU - Van Dyke, Alison L.

AU - Stampfer, Meir J.

AU - Sinha, Rashmi

AU - Sesso, Howard D.

AU - Schairer, Catherine

AU - Rosenberg, Lynn

AU - Rohan, Thomas E.

AU - Robien, Kim

AU - Purdue, Mark P.

AU - Poynter, Jenny N.

AU - Palmer, Julie R.

AU - Newton, Christina C.

AU - Linet, Martha S.

AU - Liao, Linda M.

AU - Lee, I. Min

AU - Koshiol, Jill

AU - Kitahara, Cari M.

AU - Hofmann, Jonathan N.

AU - Graubard, Barry I.

AU - Giovannucci, Edward

AU - Gaziano, J. Michael

AU - Gapstur, Susan M.

AU - Freedman, Neal D.

AU - Chong, Dawn Q.

AU - Chan, Andrew T.

AU - Buring, Julie E.

AU - Beane Freeman, Laura E.

AU - Campbell, Peter T.

AU - McGlynn, Katherine A.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Objective: Obesity and diabetes are associated with an increased liver cancer risk. However, most studies have examined all primary liver cancers or hepatocellular carcinoma, with few studies evaluating intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Thus, we examined the association between obesity and diabetes and ICC risk in a pooled analysis and conducted a systematic review/meta-analysis of the literature. Design: For the pooled analysis, we utilized the Liver Cancer Pooling Project, a consortium of 13 US-based, prospective cohort studies with data from 1,541,143 individuals (ICC cases n = 414). In our systematic review, we identified 14 additional studies. We then conducted a meta-analysis, combining the results from LCPP with results from the 5 prospective studies identified through September 2017. Results: In the LCPP, obesity and diabetes were associated with a 62% [Hazard Ratio (HR) = 1.62, 95% Confidence Interval (CI): 1.24–2.12] and an 81% (HR = 1.81, 95% CI: 1.33–2.46) increased ICC risk, respectively. In the meta-analysis of prospectively ascertained cohorts and nested case-control studies, obesity was associated with a 49% increased ICC risk [Relative Risk (RR) = 1.49, 95% CI: 1.32–1.70; n = 4 studies; I2 = 0%]. Diabetes was associated with a 53% increased ICC risk (RR = 1.53, 95% CI: 1.31–1.78; n = 6 studies). While we noted heterogeneity between studies (I2 = 67%) for diabetes, results were consistent in subgroup analyses. Results from hospital-based case–control studies (n = 9) were mostly consistent, but these studies are potentially subject to reverse causation. Conclusions: These findings suggest that obesity and diabetes are associated with increased ICC risk, highlighting similar etiologies of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. However, additional prospective studies are needed to verify these associations.

AB - Objective: Obesity and diabetes are associated with an increased liver cancer risk. However, most studies have examined all primary liver cancers or hepatocellular carcinoma, with few studies evaluating intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Thus, we examined the association between obesity and diabetes and ICC risk in a pooled analysis and conducted a systematic review/meta-analysis of the literature. Design: For the pooled analysis, we utilized the Liver Cancer Pooling Project, a consortium of 13 US-based, prospective cohort studies with data from 1,541,143 individuals (ICC cases n = 414). In our systematic review, we identified 14 additional studies. We then conducted a meta-analysis, combining the results from LCPP with results from the 5 prospective studies identified through September 2017. Results: In the LCPP, obesity and diabetes were associated with a 62% [Hazard Ratio (HR) = 1.62, 95% Confidence Interval (CI): 1.24–2.12] and an 81% (HR = 1.81, 95% CI: 1.33–2.46) increased ICC risk, respectively. In the meta-analysis of prospectively ascertained cohorts and nested case-control studies, obesity was associated with a 49% increased ICC risk [Relative Risk (RR) = 1.49, 95% CI: 1.32–1.70; n = 4 studies; I2 = 0%]. Diabetes was associated with a 53% increased ICC risk (RR = 1.53, 95% CI: 1.31–1.78; n = 6 studies). While we noted heterogeneity between studies (I2 = 67%) for diabetes, results were consistent in subgroup analyses. Results from hospital-based case–control studies (n = 9) were mostly consistent, but these studies are potentially subject to reverse causation. Conclusions: These findings suggest that obesity and diabetes are associated with increased ICC risk, highlighting similar etiologies of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. However, additional prospective studies are needed to verify these associations.

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