Hepatocellular carcinoma risk factors and disease burden in a European cohort: a nested case-control study.
BACKGROUND
To date, no attempt has been made to systematically determine the apportionment of the hepatocellular carcinoma burden in Europe or North America among established risk factors.


METHODS
Using data collected from 1992 to 2006, which included 4,409,809 person-years in the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 125 case patients with hepatocellular carcinoma, of whom 115 were matched to 229 control subjects. We calculated odds ratios (ORs) for the association of documented risk factors for hepatocellular carcinoma with incidence of this disease and estimated their importance in this European cohort.


RESULTS
Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (OR = 9.10, 95% confidence interval [CI] = 2.10 to 39.50 and OR = 13.36, 95% CI = 4.11 to 43.45, respectively), obesity (OR = 2.13, 95% CI = 1.06 to 4.29), former or current smoking (OR = 1.98, 95% CI = 0.90 to 4.39 and OR = 4.55, 95% CI = 1.90 to 10.91, respectively), and heavy alcohol intake (OR = 1.77, 95% CI = 0.73 to 4.27) were associated with hepatocellular carcinoma. Smoking contributed to almost half of all hepatocellular carcinomas (47.6%), whereas 13.2% and 20.9% were attributable to chronic HBV and HCV infection, respectively. Obesity and heavy alcohol intake contributed 16.1% and 10.2%, respectively. Almost two-thirds (65.7%, 95% CI = 50.6% to 79.3%) of hepatocellular carcinomas can be accounted for by exposure to at least one of these documented risk factors.


CONCLUSIONS
Smoking contributed to more hepatocellular carcinomas in this Europe-wide cohort than chronic HBV and HCV infections. Heavy alcohol consumption and obesity also contributed to sizeable fractions of this disease burden. These contributions may be underestimates because EPIC volunteers are likely to be more health conscious than the general population.
Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. dtrichop@hsph.harvard.edu
Dimitrios
D
Trichopoulos
Christina
C
Bamia
Pagona
P
Lagiou
Veronika
V
Fedirko
Elisabeth
E
Trepo
Mazda
M
Jenab
Tobias
T
Pischon
Ute
U
Nöthlings
Kim
K
Overved
Anne
A
Tjønneland
Malene
M
Outzen
Francoise
F
Clavel-Chapelon
Rudolf
R
Kaaks
Annekatrin
A
Lukanova
Heiner
H
Boeing
Krasimira
K
Aleksandrova
Vassiliki
V
Benetou
Dimosthenis
D
Zylis
Domenico
D
Palli
Valeria
V
Pala
Salvatore
S
Panico
Rosario
R
Tumino
Carlotta
C
Sacerdote
H Bas
HB
Bueno-De-Mesquita
Henk J
HJ
Van Kranen
Petra H M
PH
Peeters
Eiliv
E
Lund
J Ramón
JR
Quirós
Carlos A
CA
González
Maria-Jose
MJ
Sanchez Perez
Carmen
C
Navarro
Miren
M
Dorronsoro
Aurelio
A
Barricarte
Björn
B
Lindkvist
Sara
S
Regnér
Mårten
M
Werner
Göran
G
Hallmans
Kay-Tee
KT
Khaw
Nick
N
Wareham
Timothy
T
Key
Isabelle
I
Romieu
Shu-Chun
SC
Chuang
Neil
N
Murphy
Paolo
P
Boffetta
Antonia
A
Trichopoulou
Elio
E
Riboli
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000209:etiology* / Q000821:virology; D016022:Case-Control Studies; D015331:Cohort Studies; D017281:Cost of Illness; D005060:Europe / Q000453:epidemiology; D005247:Feeding Behavior; D005260:Female; D005500:Follow-Up Studies; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000453:epidemiology; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008019:Life Style; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000209:etiology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D016017:Odds Ratio; D015995:Prevalence; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*