title: Coffee Consumption and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma by Sex: The Liver Cancer Pooling Project.
abstract: BACKGROUND
  Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee-HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer.
  
  
  METHODS
  In the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, data from 1,212,893 individuals (HCC, n = 860; ICC, n = 260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards regression.
  
  
  RESULTS
  Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53-0.99; Ptrend cups/day = <0.0001). More notable reduced risk was seen among women than men (Pinteraction = 0.07). Women who consumed more than three cups of coffee per day were at a 54% lower risk of HCC (HR, 0.46; 95% CI, 0.26-0.81), whereas men had more modest reduced risk of HCC (HR, 0.93; 95% CI, 0.63-1.37). The associations were stronger for caffeinated coffee (HR>3 cups/day vs. non-drinker, 0.71; 95% CI, 0.50-1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55-1.54). There was no association between coffee consumption and ICC.
  
  
  CONCLUSIONS
  These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC.
  
  
  CONCLUSIONS
  Further research into specific coffee compounds and mechanisms that may account for these associations is needed.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. jessica.petrick@nih.gov.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Petrick
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Neal D
authors.initials: ND
authors.lastname: Freedman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Barry I
authors.initials: BI
authors.lastname: Graubard
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Vikrant V
authors.initials: VV
authors.lastname: Sahasrabuddhe
authors.affiliation: Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland.
authors.forename: Gabriel Y
authors.initials: GY
authors.lastname: Lai
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Alavanja
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Beane-Freeman
authors.affiliation: Slone Epidemiology Center at Boston University, Boston, Massachusetts.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Boggs
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Dawn Q
authors.initials: DQ
authors.lastname: Chong
authors.affiliation: Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gapstur
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: John Michael
authors.initials: JM
authors.lastname: Gaziano
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.affiliation: AARP, Washington, DC.
authors.forename: Albert R
authors.initials: AR
authors.lastname: Hollenbeck
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Lindsay Y
authors.initials: LY
authors.lastname: King
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Jill
authors.initials: J
authors.lastname: Koshiol
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: I-Min
authors.initials: IM
authors.lastname: Lee
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Martha S
authors.initials: MS
authors.lastname: Linet
authors.affiliation: Slone Epidemiology Center at Boston University, Boston, Massachusetts.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Palmer
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Jenny N
authors.initials: JN
authors.lastname: Poynter
authors.affiliation: Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Purdue
authors.affiliation: Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, DC.
authors.forename: Kim
authors.initials: K
authors.lastname: Robien
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Schairer
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Howard D
authors.initials: HD
authors.lastname: Sesso
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Sigurdson
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, New York.
authors.forename: Anne
authors.initials: A
authors.lastname: Zeleniuch-Jacquotte
authors.affiliation: Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York.
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Campbell
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: McGlynn
mesh_terms: D000368:Aged; D001650:Bile Duct Neoplasms / Q000453:epidemiology*; D001653:Bile Ducts, Intrahepatic; D002110:Caffeine / Q000008:administration & dosage / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D018281:Cholangiocarcinoma / Q000453:epidemiology*; D003069:Coffee / Q000737:chemistry; D004326:Drinking; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D014481:United States / Q000453:epidemiology
chemical_list: D003069:Coffee; D002110:Caffeine