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 ¼ 1.27; 95% CI, 1.19-1.36), IHBDC (HR ¼ 1.32; 95% CI, 1.21-1.45), and EHBDC (HR ¼ 1.13; 95% CI, 1.03-1.23), but not AVC (HR ¼ 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.
Bibliographical noteFunding Information:
AgHealth: This study was funded by the Intramural Program of the NIH, NCI (Z01 P010119), and the National Institute of Environmental Health Sciences (Z01 ES 049030-11). AHS-2: Project support was obtained from NCI Grant No. 1U01CA152939. ATBC: The ATBC Study is supported by the Intramural Research Program of the U.S. NCI, NIH, and by U.S. Public Health Service contract HHSN 261201500005C from the NCI, Department of Health and Human Services. BCDDP: The BCDDP Follow-up Study was supported by the Intramural Research Program of the NHI, NCI. COSM: This cohort is supported by the Swedish Research Council (Research Infrastructure SIMPLER), the Swedish Cancer Foundation, and by Strategic Funds from Karolinska Institutet, Stockholm, Sweden. CPS-II NC: The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II Nutrition Cohort. EPIC: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society, Denmark; Ligue Contre le Cancer, France; Institut Gustave Roussy, France; Mutuelle Generale de l'Education Nationale, France; Institut National de la Sante et de la Recherche Medicale, France; Deutsche Krebshilfe, Germany, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research, Germany; Hellenic Health Foundation, Greece; Italian Association for Research on Cancer; National Research Council, Italy; Dutch Ministry of Public Health, Welfare and Sports, the Netherlands; Netherlands Cancer Registry, the Netherlands; LK Research Funds, the Netherlands; Dutch Prevention Funds, the Netherlands; Dutch ZON (Zorg Onderzoek Nederland), the Netherlands; World Cancer Research Fund, London, UK; Statistics Netherlands, the Netherlands; European Research Council, Norway; Health Research Fund, Regional Governments of Andalucia, Asturias, Basque Country, Murcia (project no. 6236) and Navarra, ISCIII RETIC (RD06/0020/0091), Spain; Swedish Cancer Society, Sweden; Swedish Scientific Council, Sweden; Regional Government of Skane and Vasterbotten, Sweden; Cancer Research United Kingdom; Medical Research Council, United Kingdom; Stroke Association, United Kingdom, British Heart Foundation, United Kingdom; Department of Health, Food Standards Agency, United Kingdom; and Wellcome Trust; United Kingdom. We thank Bertrand Hemon for his precious help with the EPIC database. The principle investigators and funders corresponding to each of the EPIC centers that contributed cases were Kim Overvad, Anne Tjonneland (Denmark); Francoise Clavel-Chapelon (France); Heiner Boeing, Rudolf Kaaks (Germany); Antonia Trichopoulou (Greece); Vittorio Krogh, Domenico Palli, Paolo Vineis, Salvatore Panico, Rosario Tumino (Italy); Eiliv Lund (Norway); Antonio Agudo, MariaJoseSanchez,J.RamónQuirós,CarmenNavarro,AurelioBarricarte,Miren Dorronsoro (Spain); Mattias Johansson, Jonas Manjer (Sweden); H. Bas Bueno-de-Mesquita, Petra H. Peeters (The Netherlands); Timothy Key, Nick Wareham (UK); The coordination of European Prospective Investigation into Cancer and Nutrition is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the French NCI (L'Institut National du Cancer; INCA); Ligue contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santéet de la Recherche Médicale (INSERM) (France); German Cancer Aid; German Cancer Research Center (DKFZ); German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health (RTICC (DR06/0020/0091); the participating regional governments from Asturias, Andalucía, Murcia, Navarra and Vasco Country and the Catalan Institute of Oncology of Spain; Cancer Research UK; Medical Research Council, UK; the Stroke Association, UK; British Heart Foundation; Department of Health, UK; Food Standards Agency, UK; the Wellcome Trust, UK; the Hellenic Health Foundation; Italian Association for Research on Cancer; Compagnia San Paolo, Italy; Dutch Ministry of Public Health, Welfare and Sports; Dutch Ministry of Health; Dutch Prevention Funds; LK Research Funds; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); Statistics Netherlands (The Netherlands); Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane, Sweden; Nordforsk—Centre of Excellence programme. HPFS: This work was supported by grants from the NCI (UM1 CA167552, P01 CA55075), the Entertainment Industry Foundation, and the National Colorectal Cancer Research Alliance. HPFS would like to thank the participants and staff of the HPFS for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. IWHS: IWHS was funded by a grant from the NCI (R01 CA39742). JPHC: This work was supported by the National Cancer Center Research and Development Fund (since 2011) and a grant-in-aid from Cancer Research (1989–2010) from the Ministry of Health, Labor, and Welfare of Japan. MCCS: MCCS receives core funding from Cancer Council Victoria and is additionally supported by grants from the Australian NHMRC (209057, 251533, 396414, and 504715). MEC: This work was supported by the NIH (P01 CA33619 and U01 CA164973). NHS: Data used in this study was supported by an infrastructure grant (UM1 CA186107) and a program project grant that funds cancer research (P01 CA87969). NHS would like to thank the participants and staff of the NHS for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. NIH-AARP: This research was supported [in part] by the Intramural Research Program of the NIH, NCI. Cancer incidence data from the Atlanta metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA. Cancer incidence data from California were collected by the California Cancer Registry, California Department of Public Health's Cancer Surveillance and Research Branch, Sacramento, CA. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, Lansing, MI. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System (Miami, FL) under contract with the Florida Department of Health, Tallahassee, FL. The views expressed herein are solely those of the authors and do not necessarily reflect those of the FCDC or FDOH. Cancer incidence data from Louisiana were collected by the Louisiana Tumor Registry, Louisiana State University Health Sciences Center School of Public Health, New Orleans, LA. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, The Rutgers Cancer Institute of New Jersey, New Brunswick, NJ. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry, Raleigh, NC. Cancer incidence data from Pennsylvania were supplied by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, PA. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations or conclusions. Cancer incidence data from Arizona were collected by the
Arizona Cancer Registry, Division of Public Health Services, Arizona Department of Health Services, Phoenix, AZ. Cancer incidence data from Texas were collected by the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, TX. Cancer incidence data from Nevada were collected by the Nevada Central Cancer Registry, Division of Public and Behavioral Health, State of Nevada Department of Health and Human Services, Carson City, NV. NYUWHS: The NYUWHS is supported by grants UM1 CA182934 and P30 CA16087 from the NCI and by grant P30 ES000260 from the National Institute of Environmental Health Sciences. PHS: PHS is supported by grants from the NCI (CA-34933, CA-40360, and CA-097193) and from the National Heart, Lung, and Blood Institute (HL-26490 and HL-34595), NIH, Bethesda, MD. PLCO: The PLCO Cancer Screening Trial is supported by contracts from the NCI. RERF: The Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan is a public interest foundation funded by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the US Department of Energy (DOE). The research was also funded in part through DOE award DE-HS0000031 to the National Academy of Sciences. This publication was supported by RERF Research Protocol A2-13. The views of the authors do not necessarily reflect those of the two governments. SCHS: This study is supported by the NCI (R01CA080205, R01CA144034, UM1CA182876). SCS: The Shanghai Cohort Study is supported by the NCI (R01CA043092, R01CA144034, UM1CA182876). SISTER: The Sister Study is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ZO1-ES-044005). Support for data collection and study and data management are provided by Social & Scientific Systems, Inc., and Westat, Inc., Durham, NC. SMC: This cohort is supported by the Swedish Research Council (Research Infrastructure SIMPLER), the Swedish Cancer Foundation, and by Strategic Funds from Karolinska Institutet, Stockholm, Sweden. VITAL: The VITAL study was supported by the NIH grant K05-CA154337 (NCI and Office of Dietary Supplements). WHI: The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services
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