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Title: Smoking, Alcohol, and Biliary Tract Cancer Risk: A Pooling Project of 26 Prospective Studies

Abstract

Abstract Background Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear. Methods We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random-effects meta-analysis produced summary estimates. All statistical tests were two-sided. Results Over a period of 38 369 156 person-years of follow-up, 1391 gallbladder, 758 intrahepatic bile duct, 1208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (eg, current vs never smokers HR = 1.69, 95% CI = 1.34 to 2.13 and 2.22, 95% CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all Ptrend < .01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (eg, >40 cigarettes per day vs never smokers HR = 2.15, 95 % CI = 1.15 to 4.00; Ptrend = .001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepaticmore » bile duct cancer, with increased risk for individuals consuming five or more vs zero drinks per day (HR = 2.35, 95%CI = 1.46 to 3.78; Ptrend = .04). There was evidence of statistical heterogeneity among several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers. Conclusions Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract.« less

Authors:
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  1. See the Notes section for the full list of authors’ affiliations
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1564293
Grant/Contract Number:  
HS0000031
Resource Type:
Published Article
Journal Name:
JNCI, Journal of the National Cancer Institute
Additional Journal Information:
Journal Name: JNCI, Journal of the National Cancer Institute; Journal ID: ISSN 0027-8874
Publisher:
Oxford University Press
Country of Publication:
United States
Language:
English

Citation Formats

McGee, Emma E., Jackson, Sarah S., Petrick, Jessica L., Van Dyke, Alison L., Adami, Hans-Olov, Albanes, Demetrius, Andreotti, Gabriella, Beane-Freeman, Laura E., de Gonzalez, Amy Berrington, Buring, Julie E., Chan, Andrew T., Chen, Yu, Fraser, Gary E., Freedman, Neal D., Gao, Yu-Tang, Gapstur, Susan M., Gaziano, J. Michael, Giles, Graham G., Grant, Eric J., Grodstein, Francine, Hartge, Patricia, Jenab, Mazda, Kitahara, Cari M., Knutsen, Synnove F., Koh, Woon-Puay, Larsson, Susanna C., Lee, I-Min, Liao, Linda M., Luo, Juhua, Milne, Roger L., Monroe, Kristine R., Neuhouser, Marian L., O’Brien, Katie M., Peters, Ulrike, Poynter, Jenny N., Purdue, Mark P., Robien, Kim, Sandler, Dale P., Sawada, Norie, Schairer, Catherine, Sesso, Howard D., Simon, Tracey G., Sinha, Rashmi, Stolzenberg-Solomon, Rachael, Tsugane, Shoichiro, Wang, Renwei, Weiderpass, Elisabete, Weinstein, Stephanie J., White, Emily, Wolk, Alicja, Yuan, Jian-Min, Zeleniuch-Jacquotte, Anne, Zhang, Xuehong, Zhu, Bin, McGlynn, Katherine A., Campbell, Peter T., and Koshiol, Jill. Smoking, Alcohol, and Biliary Tract Cancer Risk: A Pooling Project of 26 Prospective Studies. United States: N. p., 2019. Web. doi:10.1093/jnci/djz103.
McGee, Emma E., Jackson, Sarah S., Petrick, Jessica L., Van Dyke, Alison L., Adami, Hans-Olov, Albanes, Demetrius, Andreotti, Gabriella, Beane-Freeman, Laura E., de Gonzalez, Amy Berrington, Buring, Julie E., Chan, Andrew T., Chen, Yu, Fraser, Gary E., Freedman, Neal D., Gao, Yu-Tang, Gapstur, Susan M., Gaziano, J. Michael, Giles, Graham G., Grant, Eric J., Grodstein, Francine, Hartge, Patricia, Jenab, Mazda, Kitahara, Cari M., Knutsen, Synnove F., Koh, Woon-Puay, Larsson, Susanna C., Lee, I-Min, Liao, Linda M., Luo, Juhua, Milne, Roger L., Monroe, Kristine R., Neuhouser, Marian L., O’Brien, Katie M., Peters, Ulrike, Poynter, Jenny N., Purdue, Mark P., Robien, Kim, Sandler, Dale P., Sawada, Norie, Schairer, Catherine, Sesso, Howard D., Simon, Tracey G., Sinha, Rashmi, Stolzenberg-Solomon, Rachael, Tsugane, Shoichiro, Wang, Renwei, Weiderpass, Elisabete, Weinstein, Stephanie J., White, Emily, Wolk, Alicja, Yuan, Jian-Min, Zeleniuch-Jacquotte, Anne, Zhang, Xuehong, Zhu, Bin, McGlynn, Katherine A., Campbell, Peter T., & Koshiol, Jill. Smoking, Alcohol, and Biliary Tract Cancer Risk: A Pooling Project of 26 Prospective Studies. United States. doi:10.1093/jnci/djz103.
McGee, Emma E., Jackson, Sarah S., Petrick, Jessica L., Van Dyke, Alison L., Adami, Hans-Olov, Albanes, Demetrius, Andreotti, Gabriella, Beane-Freeman, Laura E., de Gonzalez, Amy Berrington, Buring, Julie E., Chan, Andrew T., Chen, Yu, Fraser, Gary E., Freedman, Neal D., Gao, Yu-Tang, Gapstur, Susan M., Gaziano, J. Michael, Giles, Graham G., Grant, Eric J., Grodstein, Francine, Hartge, Patricia, Jenab, Mazda, Kitahara, Cari M., Knutsen, Synnove F., Koh, Woon-Puay, Larsson, Susanna C., Lee, I-Min, Liao, Linda M., Luo, Juhua, Milne, Roger L., Monroe, Kristine R., Neuhouser, Marian L., O’Brien, Katie M., Peters, Ulrike, Poynter, Jenny N., Purdue, Mark P., Robien, Kim, Sandler, Dale P., Sawada, Norie, Schairer, Catherine, Sesso, Howard D., Simon, Tracey G., Sinha, Rashmi, Stolzenberg-Solomon, Rachael, Tsugane, Shoichiro, Wang, Renwei, Weiderpass, Elisabete, Weinstein, Stephanie J., White, Emily, Wolk, Alicja, Yuan, Jian-Min, Zeleniuch-Jacquotte, Anne, Zhang, Xuehong, Zhu, Bin, McGlynn, Katherine A., Campbell, Peter T., and Koshiol, Jill. Sat . "Smoking, Alcohol, and Biliary Tract Cancer Risk: A Pooling Project of 26 Prospective Studies". United States. doi:10.1093/jnci/djz103.
@article{osti_1564293,
title = {Smoking, Alcohol, and Biliary Tract Cancer Risk: A Pooling Project of 26 Prospective Studies},
author = {McGee, Emma E. and Jackson, Sarah S. and Petrick, Jessica L. and Van Dyke, Alison L. and Adami, Hans-Olov and Albanes, Demetrius and Andreotti, Gabriella and Beane-Freeman, Laura E. and de Gonzalez, Amy Berrington and Buring, Julie E. and Chan, Andrew T. and Chen, Yu and Fraser, Gary E. and Freedman, Neal D. and Gao, Yu-Tang and Gapstur, Susan M. and Gaziano, J. Michael and Giles, Graham G. and Grant, Eric J. and Grodstein, Francine and Hartge, Patricia and Jenab, Mazda and Kitahara, Cari M. and Knutsen, Synnove F. and Koh, Woon-Puay and Larsson, Susanna C. and Lee, I-Min and Liao, Linda M. and Luo, Juhua and Milne, Roger L. and Monroe, Kristine R. and Neuhouser, Marian L. and O’Brien, Katie M. and Peters, Ulrike and Poynter, Jenny N. and Purdue, Mark P. and Robien, Kim and Sandler, Dale P. and Sawada, Norie and Schairer, Catherine and Sesso, Howard D. and Simon, Tracey G. and Sinha, Rashmi and Stolzenberg-Solomon, Rachael and Tsugane, Shoichiro and Wang, Renwei and Weiderpass, Elisabete and Weinstein, Stephanie J. and White, Emily and Wolk, Alicja and Yuan, Jian-Min and Zeleniuch-Jacquotte, Anne and Zhang, Xuehong and Zhu, Bin and McGlynn, Katherine A. and Campbell, Peter T. and Koshiol, Jill},
abstractNote = {Abstract Background Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear. Methods We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random-effects meta-analysis produced summary estimates. All statistical tests were two-sided. Results Over a period of 38 369 156 person-years of follow-up, 1391 gallbladder, 758 intrahepatic bile duct, 1208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (eg, current vs never smokers HR = 1.69, 95% CI = 1.34 to 2.13 and 2.22, 95% CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all Ptrend < .01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (eg, >40 cigarettes per day vs never smokers HR = 2.15, 95 % CI = 1.15 to 4.00; Ptrend = .001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming five or more vs zero drinks per day (HR = 2.35, 95%CI = 1.46 to 3.78; Ptrend = .04). There was evidence of statistical heterogeneity among several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers. Conclusions Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract.},
doi = {10.1093/jnci/djz103},
journal = {JNCI, Journal of the National Cancer Institute},
number = ,
volume = ,
place = {United States},
year = {2019},
month = {5}
}

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DOI: 10.1093/jnci/djz103

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Works referenced in this record:

Baseline Characteristics of Participants in the Women's Health Study
journal, January 2000

  • Rexrode, Kathryn M.; Lee, I-Min; Cook, Nancy R.
  • Journal of Women's Health & Gender-Based Medicine, Vol. 9, Issue 1
  • DOI: 10.1089/152460900318911

The Agricultural Health Study.
journal, April 1996

  • Alavanja, M. C.; Sandler, D. P.; McMaster, S. B.
  • Environmental Health Perspectives, Vol. 104, Issue 4
  • DOI: 10.1289/ehp.96104362

Design and Serendipity in Establishing a Large Cohort with Wide Dietary Intake Distributions
journal, December 2001

  • Schatzkin, Arthur; Subar, Amy F.; Thompson, Frances E.
  • American Journal of Epidemiology, Vol. 154, Issue 12
  • DOI: 10.1093/aje/154.12.1119

Body Fat Distribution and 5-Year Risk of Death in Older Women
journal, January 1993


Singapore Chinese Health Study: Development, Validation, and Calibration of the Quantitative Food Frequency Questionnaire
journal, March 2001

  • Hankin, Jean H.; Stram, Daniel O.; Arakawa, Kazuko
  • Nutrition and Cancer, Vol. 39, Issue 2
  • DOI: 10.1207/S15327914nc392_5

A Multiethnic Cohort in Hawaii and Los Angeles: Baseline Characteristics
journal, February 2000


Alcohol consumption and risk of gallstone disease: a meta-analysis
journal, January 2017

  • Wang, Jiantao; Duan, Xiaolin; Li, Bingrong
  • European Journal of Gastroenterology & Hepatology, Vol. 29, Issue 4
  • DOI: 10.1097/MEG.0000000000000803

Cohort Profile: The Adventist Health Study-2 (AHS-2)
journal, August 2007

  • Butler, Terry L.; Fraser, Gary E.; Beeson, W. Lawrence
  • International Journal of Epidemiology, Vol. 37, Issue 2
  • DOI: 10.1093/ije/dym165

Implementation of the women's health initiative study design
journal, October 2003


Proportional hazards tests and diagnostics based on weighted residuals
journal, January 1994


Risk Factors for Intrahepatic and Extrahepatic Cholangiocarcinoma in the United States: A Population-Based Case-Control Study
journal, October 2007

  • Welzel, Tania M.; Graubard, Barry I.; El–Serag, Hashem B.
  • Clinical Gastroenterology and Hepatology, Vol. 5, Issue 10
  • DOI: 10.1016/j.cgh.2007.05.020

Comparison of baseline characteristics and mortality experience of participants and nonparticipants in a randomized clinical trial
journal, December 2002


Tobacco carcinogens, their biomarkers and tobacco-induced cancer
journal, December 2003

  • Hecht, Stephen S.
  • Nature Reviews Cancer, Vol. 3, Issue 10
  • DOI: 10.1038/nrc1190

Risk Factors for Intrahepatic and Extrahepatic Cholangiocarcinoma: A Hospital-Based Case?Control Study
journal, May 2007


The American Cancer Society Cancer Prevention Study II Nutrition Cohort: Rationale, study design, and baseline characteristics
journal, April 2002

  • Calle, Eugenia E.; Rodriguez, Carmen; Jacobs, Eric J.
  • Cancer, Vol. 94, Issue 9
  • DOI: 10.1002/cncr.101970

Alcohol and cancer
journal, February 2006


Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012: Globocan 2012
journal, October 2014

  • Ferlay, Jacques; Soerjomataram, Isabelle; Dikshit, Rajesh
  • International Journal of Cancer, Vol. 136, Issue 5
  • DOI: 10.1002/ijc.29210

Cancer incidence and mortality attributable to alcohol consumption: Alcohol Attributable Cancers
journal, October 2015

  • Praud, Delphine; Rota, Matteo; Rehm, Jürgen
  • International Journal of Cancer, Vol. 138, Issue 6
  • DOI: 10.1002/ijc.29890

Invited Commentary: Consolidating Data Harmonization--How to Obtain Quality and Applicability?
journal, July 2011

  • Fortier, I.; Doiron, D.; Burton, P.
  • American Journal of Epidemiology, Vol. 174, Issue 3
  • DOI: 10.1093/aje/kwr194

Design of the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial
journal, December 2000


Cigarette smoking, alcohol drinking and the risk of gallbladder cancer death: A prospective cohort study in Japan
journal, January 2007

  • Yagyu, Kiyoko; Kikuchi, Shogo; Obata, Yuki
  • International Journal of Cancer, Vol. 122, Issue 4
  • DOI: 10.1002/ijc.23159

The effect of smoking on the risk of gallbladder cancer: a meta-analysis of observational studies
journal, January 2013

  • Wenbin, Ding; Zhuo, Chen; Zhibing, Ming
  • European Journal of Gastroenterology & Hepatology, Vol. 25, Issue 3
  • DOI: 10.1097/MEG.0b013e32835a870b

Alcohol consumption and site-specific cancer risk: a comprehensive dose–response meta-analysis
journal, November 2014

  • Bagnardi, V.; Rota, M.; Botteri, E.
  • British Journal of Cancer, Vol. 112, Issue 3
  • DOI: 10.1038/bjc.2014.579

Quantifying heterogeneity in a meta-analysis
journal, January 2002

  • Higgins, Julian P. T.; Thompson, Simon G.
  • Statistics in Medicine, Vol. 21, Issue 11
  • DOI: 10.1002/sim.1186

Combined effects of obesity and physical activity in predicting mortality among men
journal, November 2008


Smoking, alcohol consumption, and the risk of extrahepatic cholangiocarcinoma: A meta-analysis
journal, January 2013


The Sister Study Cohort: Baseline Methods and Participant Characteristics
journal, December 2017

  • Sandler, Dale P.; Hodgson, M. Elizabeth; Deming-Halverson, Sandra L.
  • Environmental Health Perspectives, Vol. 125, Issue 12
  • DOI: 10.1289/EHP1923

Biliary tract cancer incidence in the United States-Demographic and temporal variations by anatomic site: Biliary tract cancer incidence in the US by anatomic site
journal, April 2013

  • Castro, Felipe A.; Koshiol, Jill; Hsing, Ann W.
  • International Journal of Cancer, Vol. 133, Issue 7
  • DOI: 10.1002/ijc.28161

Effect of dietary ethanol on gallbladder absorption and cholesterol gallstone formation in the prairie dog
journal, April 1991

  • Kurtin, William E.; Schwesinger, Wayne H.; Stewart, Ronald M.
  • The American Journal of Surgery, Vol. 161, Issue 4
  • DOI: 10.1016/0002-9610(91)91114-X

Menopausal Estrogen and Estrogen-Progestin Replacement Therapy and Breast Cancer Risk
journal, January 2000


Biliary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in the rat
journal, January 1992


European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection
journal, December 2002

  • Riboli, E.; Hunt, Kj; Slimani, N.
  • Public Health Nutrition, Vol. 5, Issue 6b
  • DOI: 10.1079/PHN2002394

Changing pattern of epidemiology in intrahepatic cholangiocarcinoma: Correspondence
journal, July 2014


Risk factors for extrahepatic biliary tract carcinoma in men: medical conditions and lifestyle: Results from a European multicentre case–control study
journal, January 2007


A Prospective Study of Endogenous Estrogens and Breast Cancer in Postmenopausal Women
journal, February 1995

  • Toniolo, P. G.; Levitz, M.; Zeleniuch-Jacquotte, A.
  • JNCI Journal of the National Cancer Institute, Vol. 87, Issue 3
  • DOI: 10.1093/jnci/87.3.190

VITamins And Lifestyle Cohort Study: Study Design and Characteristics of Supplement Users
journal, January 2004


Immunomodulatory effects of cigarette smoke
journal, March 1998


Risk factors for extrahepatic bile duct cancers: Los Angeles County, California (USA)
journal, May 1994

  • Chow, Wong-Ho; McLaughlin, Joseph K.; Menck, Herman R.
  • Cancer Causes & Control, Vol. 5, Issue 3
  • DOI: 10.1007/BF01830247

Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project
journal, March 2018

  • Petrick, Jessica L.; Campbell, Peter T.; Koshiol, Jill
  • British Journal of Cancer, Vol. 118, Issue 7
  • DOI: 10.1038/s41416-018-0007-z

Smoking and risk of cholangiocarcinoma: a systematic review and meta-analysis
journal, August 2017


Intrahepatic Cholangiocarcinoma: Rising Frequency, Improved Survival, and Determinants of Outcome After Resection
journal, January 2008


A review of human carcinogens—Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish
journal, November 2009


Joint Analysis of Site-Specific Cance Risks for the Atomic Bomb Survivors
journal, May 1993

  • Pierce, Donald A.; Preston, Dale L.
  • Radiation Research, Vol. 134, Issue 2
  • DOI: 10.2307/3578452

Risk factors for gallbladder cancer: A polish case-control study
journal, July 1992

  • Zatonski, Witold A.; La Vecchia, Carlo; Przewozniak, Krzysztof
  • International Journal of Cancer, Vol. 51, Issue 5
  • DOI: 10.1002/ijc.2910510508

The JPHC Study: Design and Some Findings on the Typical Japanese Diet
journal, August 2014

  • Tsugane, S.; Sawada, N.
  • Japanese Journal of Clinical Oncology, Vol. 44, Issue 9
  • DOI: 10.1093/jjco/hyu096

Cigarette Smoking and Cancer Risk: Modeling Total Exposure and Intensity
journal, June 2007

  • Lubin, J. H.; Alavanja, M. C. R.; Caporaso, N.
  • American Journal of Epidemiology, Vol. 166, Issue 4
  • DOI: 10.1093/aje/kwm089

The antecedents of biliary cancer: a primary care case–control study in the United Kingdom
journal, November 2008

  • Grainge, M. J.; West, J.; Solaymani-Dodaran, M.
  • British Journal of Cancer, Vol. 100, Issue 1
  • DOI: 10.1038/sj.bjc.6604765

Smoking, Alcohol Consumption, and Risks for Biliary Tract Cancer and Intrahepatic Bile Duct Cancer
journal, January 2019

  • Makiuchi, Takeshi; Sobue, Tomotaka; Kitamura, Tetsuhisa
  • Journal of Epidemiology, Vol. 29, Issue 5
  • DOI: 10.2188/jea.JE20180011

Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: A population-based study in SEER-Medicare
journal, October 2017


Studies of the Mortality of A-Bomb Survivors: I. Plan of Study and Mortality in the Medical Subsample (Selection I), 1950-1958
journal, March 1962

  • Beebe, Gilbert W.; Ishida, Morihiro; Jablon, Seymour
  • Radiation Research, Vol. 16, Issue 3
  • DOI: 10.2307/3571157

Coffee, Caffeine, and Cardiovascular Disease in Men
journal, October 1990

  • Grobbee, Diederick E.; Rimm, Eric B.; Giovannucci, Edward
  • New England Journal of Medicine, Vol. 323, Issue 15
  • DOI: 10.1056/NEJM199010113231504

Gallstones and the risk of biliary tract cancer: a population-based study in China
journal, November 2007


Long-term Fatty Fish Consumption and Renal Cell Carcinoma Incidence in Women
journal, September 2006


Traditional reviews, meta-analyses and pooled analyses in epidemiology
journal, February 1999

  • Blettner, M.
  • International Journal of Epidemiology, Vol. 28, Issue 1
  • DOI: 10.1093/ije/28.1.1

Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma
journal, April 1992