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Cancer Res. 2019 Aug 1;79(15):3973-3982. doi: 10.1158/0008-5472.CAN-19-0459. Epub 2019 May 21.

Anthropometric Risk Factors for Cancers of the Biliary Tract in the Biliary Tract Cancers Pooling Project.

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Division of Cancer Epidemiology and Genetics, NCI, Bethesda, Maryland.
Division of Cancer Epidemiology and Genetics, NCI, Bethesda, Maryland.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Health Management and Health Economics, University of Oslo, Oslo, Norway.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Department of Population Health and Perlmutter Cancer Center, New York University School of Medicine, New York, New York.
School of Public Health, Loma Linda University, Loma Linda, California.
Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
Behavioral and Epidemiology Research Group, American Cancer Society, Inc., Atlanta, Georgia.
Boston Veteran Affairs Healthcare System, Boston, Massachusetts.
Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia.
Department of Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan.
Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore.
Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Epidemiology and Biostatistics, School of Public Health, Indiana University Bloomington, Bloomington, Indiana.
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
Cancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
Department of Epidemiology, University of Washington, Seattle, Washington.
Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, District of Columbia.
Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
International Agency for Research on Cancer (IARC), Lyon, France.
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.


Biliary tract cancers are rare but highly fatal with poorly understood etiology. Identifying potentially modifiable risk factors for these cancers is essential for prevention. Here we estimated the relationship between adiposity and cancer across the biliary tract, including cancers of the gallbladder (GBC), intrahepatic bile ducts (IHBDC), extrahepatic bile ducts (EHBDC), and the ampulla of Vater (AVC). We pooled data from 27 prospective cohorts with over 2.7 million adults. Adiposity was measured using baseline body mass index (BMI), waist circumference, hip circumference, waist-to-hip, and waist-to-height ratios. HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models adjusted for sex, education, race, smoking, and alcohol consumption with age as the time metric and the baseline hazard stratified by study. During 37,883,648 person-years of follow-up, 1,343 GBC cases, 1,194 EHBDC cases, 784 IHBDC cases, and 623 AVC cases occurred. For each 5 kg/m2 increase in BMI, there were risk increases for GBC (HR = 1.27; 95% CI, 1.19-1.36), IHBDC (HR = 1.32; 95% CI, 1.21-1.45), and EHBDC (HR = 1.13; 95% CI, 1.03-1.23), but not AVC (HR = 0.99; 95% CI, 0.88-1.11). Increasing waist circumference, hip circumference, waist-to-hip ratio, and waist-to-height ratio were associated with GBC and IHBDC but not EHBDC or AVC. These results indicate that adult adiposity is associated with an increased risk of biliary tract cancer, particularly GBC and IHBDC. Moreover, they provide evidence for recommending weight maintenance programs to reduce the risk of developing these cancers. SIGNIFICANCE: These findings identify a correlation between adiposity and biliary tract cancers, indicating that weight management programs may help minimize the risk of these diseases.

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