Laurie Barclay, MD
Désirée Lie, MD, MSEd
Brande Nicole Martin
July 1, 2008 Higher coffee consumption was
associated with lower liver cancer risk but
higher levels of gamma-glutamyltransferase (GGT)
may increase risk for this disease, according to
the results of a study reported in the July issue of Hepatology.
"Only three Japanese prospective studies have
suggested an inverse association between coffee
drinking and liver cancer risk," write Gang Hu,
from the Department of Public Health, University
of Helsinki in Finland, and colleagues. "No
prospective studies on the association between
... GGT and liver cancer risk have been reported.
We aimed to determine the single and joint
associations of coffee consumption and serum GGT
with the risk of primary liver cancer."
The study cohort consisted of 60,323 Finns who
were 25 to 74 years of age and free of any cancer
at enrollment. Median follow-up was 19.3 years
(interquartile range, 9.3 - 29.2 years). Incident
liver cancer was diagnosed in 128 participants
during follow-up. Hazard ratios for liver cancer
risk as a function of coffee consumption were
multivariable-adjusted for age, sex, alcohol
consumption, education, smoking, diabetes and
chronic liver disease at baseline and during
follow-up, body mass index was assessed.
Adjusted hazard ratios of liver cancer in
participants who drank 0 to 1, 2 to 3, 4 to 5, 6
to 7, and more than 8 cups of coffee daily were
1.00, 0.66, 0.44, 0.38, and 0.32, respectively (P
for trend = .003), and further adjustment for
serum GGT in subgroup analysis affected the
results only slightly. For the highest vs the
lowest quartile of serum GGT, the
multivariable-adjusted and coffee-adjusted hazard
ratio of liver cancer was 3.13 (95% confidence interval, 1.22 - 8.07).
Stratification by baseline factors did not
abolish the multivariable-adjusted inverse
association between coffee consumption and liver
cancer risk; these factors included age younger
than 50 years and 50 years and older, current
smoker/never smoked/ever smoked, alcohol
drinker/never drinker, obese/nonobese, and the
highest/lowest 3 quartiles of serum GGT. Risk was
increased nearly 9-fold for the combination of
very low coffee consumption and high level of serum GGT.
"Coffee drinking has an inverse and graded
association with the risk of liver cancer," the
study authors write. "High serum GGT is
associated with an increased risk of liver cancer."
Limitations of this study include use of
self-reported data on coffee intake only at
baseline; lack of data about other main sources
of caffeine; no data on history of either
hepatitis B virus or hepatitis C virus infections
at baseline; use of only a dichotomized measure
of alcohol consumption in the whole sample; and
inability to completely exclude the effects of
residual confounding due to measurement error.
"The biological mechanisms behind the association
of coffee consumption with the risk of liver
cancer are not understood at present," the study
authors conclude. "It would be interesting to
find out whether the modification of coffee
drinking would modify the risk of liver cancer in
people positive for either HBV [hepatitis B
virus] or HCV [hepatitis C virus] infection."
In an accompanying editorial, Carlo La Vecchia,
from Universitá degli Studi di Milano in Milan,
Italy, notes the difficulties in translating the
inverse relation between coffee drinking and
liver cancer risk into potential implications for
preventing liver cancer by increasing coffee consumption.
"Together with avoidance of lung cancer through
tobacco control, primary liver cancer is the
other common neoplasm which is most largely
avoidable, through HBV vaccination, control of
HCV transmission, and reduction of alcohol
drinking," Dr. La Vecchia writes. "These three
measures can, in principle, avoid more than 90%
of primary liver cancers worldwide. Whether
coffee drinking has an additional role in liver
cancer prevention remains open to discussion, but
in any case any such role would be limited if
not negligible as compared to that achievable
through control of HBV, HCV, and alcohol
consumption, which are the major recognized risk factors for liver cancer."
The Finnish Academy and Special Research Funds of
the Social Welfare and Health Board, City of
Oulu, supported this study. The authors have
disclosed no relevant financial relationships.
The Italian Association for Cancer Research and
the Italian League Against Cancer supported this work.
Hepatology. 2008;48:7-9, 129-136.
Clinical Context
According to the current authors, liver cancer is
the third most common cause of death from cancer
worldwide. The incidence rate is high in western
and central Africa and southeastern and eastern
Asia and low in most developed countries except
Japan, and hepatitis B and C virus infections
have been identified as causative factors in more
than 75% of cases. However, according to the
current authors, coffee consumption has been
found to be inversely related to risk for primary
liver cancer, whereas GGT levels has been linked
to increased risk. Finns drink coffee daily and
have a higher per capita consumption of coffee
(11.4 kg/year) than others such as the Japanese
(3.2 kg/year) and Americans (4.1 kg/year). The
prevalence of primary liver cancer and of
hepatitis B and C virus infection is low in the
Finnish population, making it a good setting to
test the hypothesis that coffee consumption
protects against primary liver cancer.
This is a population-based prospective cohort
study to examine the association between coffee
consumption and GGT level and risk for primary
liver cancer during 19 years of follow-up in the Finn population.
Study Highlights
* 7 independent surveys were conducted in 6
geographic areas of Finland between 1972 and
2002, and a randomly selected sample was drawn
during 2 of the years, and stratified by area,
sex, and age, according to the World Health
Organization MONICA [MONItoring trends and
determinants of CArdiovascular disease] protocol.
* Subjects included were those 25 to 64 years
of age and 65 to 74 years with a total sample size of 62,015.
* After excluding those with any history of
cancer and incomplete data, 29,286 men and 31,037
women were analyzed and observed.
* Participants completed a questionnaire at
baseline for medical history, lifestyle, and demographics.
* Smoking was categorized as never,
ex-smoker, and current smoker; diabetes was
documented from disease registers, and
participants were asked "How many cups of coffee do you drink daily?".
* 1 cup of coffee in Finland is 1 dL.
* Alcohol consumption was categorized as
abstainers and users and also into 4 subgroups of consumption.
* Body mass index was calculated.
* GGT was determined from venous blood using a kinetic method.
* All cancers were identified using the
Finnish Cancer Registry, and survey cohorts were
followed with computer-based registry linkage to 2006.
* Primary liver cancer included all types of
cancer, such as hepatocellular carcinoma,
cholangiocarcinoma, and adenocarcinoma.
* Mean age was 45 years, mean body mass index
was 26 kg/m2, 60% to 72% were alcohol drinkers,
24% to 60% were current smokers, 7% had incident
diabetes during follow-up, and less than 0.4% had chronic liver disease.
* Median coffee consumption was 5.0 cups, and
only 6.9% reported no coffee consumption and 3.3% reported 1 cup a day.
* Coffee consumption was positively
associated with body mass index and smoking and
inversely related to education and serum GGT.
* After excluding those with chronic liver
disease, the multivariate adjusted hazard ratios
during the first 2 years of follow-up for liver
cancer for those who drank 0 to 1, 2 to 3, 4 to
5, 6 to 7, and 8 or more cups daily were 1.00,
0.66, 0.43, 0.42, and 0.35, respectively (P for trend .013).
* For the entire cohort for a median
follow-up of 19.3 years, the adjusted hazard
ratios for 0 to 1, 2 to 3, 4 to 5, 5 to 6, 6 to 7
and 8 or more cups daily were 1.00, 0.66, 0.44,
0.38, and 0.32 (P for trend .003).
* When analysis was restricted to 1982 to
2002 (n = 37,842) for a median of 14.3 years of
follow-up, the multivariate and GGT adjusted odds
of liver cancer for 0 to 1, 2 to 3, 4 to 5, 6 to
7 and 8 or more cups daily were 1.00, 0.53, 0.41,
0.29, and 0.22 respectively (P for trend .018).
* A significant positive association was
found for serum GGT and liver cancer risk, with a
hazard ratio of 3.13 for the highest vs the
lowest quartile of GGT, excluding those with
chronic liver disease or those who died from any
cause did not change this association.
* No interactions were found for age group,
smoking, body mass index, and alcohol consumption.
* The association did not change for filtered vs pot-boiled coffee.
* Those who drank the least coffee (0-1 cups
daily) and in the highest quartile of serum GGT
level had a 9.2 times increased risk for liver cancer.
* There was no significant interaction
between coffee intake and GGT level for the risk for liver cancer.
* The authors concluded that coffee
consumption and serum GGT were independently
associated with liver cancer risk.
MEDSCAPE
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