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MEDICAL: DISEASES: CANCER : LIVER CANCER :

META-ANALYSIS :

MEDICAL: CONDITIONS: OBESITY :

JOURNAL ARTICLE:

Overweight, Obesity and Risk of Liver Cancer:
A Meta-Analysis of Cohort Studies

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Overweight, obesity and risk of liver cancer: a meta-analysis of cohort 
studies
S C Larsson1,* and A Wolk1
Br J Cancer. 2007 Oct 8; 97(7): 10051008.
Published online 2007 Aug 14. doi:  10.1038/sj.bjc.6603932

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360408/

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ABSTRACT

Cohort studies of excess body weight and risk of liver cancer were 
identified for a meta-analysis by searching MEDLINE and EMBASE databases 
from 1966 to June 2007 and the reference lists of retrieved articles. 
Results from individual studies were combined using a random-effects 
model. We identified 11 cohort studies, of which seven on overweight (with 
a total of 5037 cases) and 10 on obesity (with 6042 cases) were suitable 
for meta-analysis. Compared with persons of normal weight, the summary 
relative risks of liver cancer were 1.17 (95% confidence interval (CI): 
1.021.34) for those who were overweight and 1.89 (95% CI: 1.512.36) for 
those who were obese. This meta-analysis finds that excess body weight is 
associated with an increased risk of liver cancer.

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Keywords: body mass index, cohort studies, liver cancer, meta-analysis, 
obesity, review

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Although relatively rare in the United States and other developed 
countries, liver cancer is the third most common cause of death from 
cancer worldwide (Parkin et al, 2005). It is rarely detected early and is 
often fatal within a few months of diagnosis. The 5-year survival rate is 
only about 611% (Coleman et al, 2003; Ries et al, 2006). The age-adjusted 
incidence and mortality rates of liver cancer have been increasing rapidly 
in the United States since the mid-1980s (Ries et al, 2006). While 
approximately half of this increase can be attributable to hepatitis C 
virus infection, a minimal or no increase has been related to hepatitis B 
virus and alcoholic liver disease (El-Serag and Mason, 2000; Hassan et al, 
2002). Given that about half of the increase in liver cancer incidence is 
not related to hepatitis, the major risk factor in a significant 
proportion of the cases has yet to be identified.

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Coinciding with the rising incidence of liver cancer, the prevalence of 
obesity has been increasing markedly over the past two decades worldwide 
(Larsson and Wolk, 2006). Obesity has been recognised as a risk factor for 
several malignancies, including cancer of the breast (in premenopausal 
women), endometrium, kidney (renal cell), colon, pancreas, gallbladder, 
and esophagus (adenocarcinoma) (IARC, 2002; Larsson et al, 2007; Larsson 
and Wolk, 2007). Accumulating epidemiologic evidence also indicates that 
excess body weight may be a risk factor for liver cancer, but the evidence 
has not been quantitatively summarised. We have therefore quantitatively 
assessed the associations of overweight and obesity with liver cancer risk 
in a meta-analysis of cohort studies.

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snip

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DISCUSSION

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This is the first meta-analysis on overweight and obesity in relation to 
liver cancer risk and it indicates that excess body weight is associated 
with increased risk. Summary results showed that the risk was 17 and 89% 
higher among persons who were overweight and obese, respectively, compared 
with those of normal weight. The relation between obesity and liver cancer 
seemed to be stronger in men than in women.

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Although there was statistically significant heterogeneity among study 
results, the relation between obesity and risk of liver cancer was 
consistent. Differences in the relative risk estimates were largely in the 
magnitude rather than the direction of the association. All but 1 out of 
the 14 relative risk estimates for the association between obesity and 
liver cancer were above one (ranging from 1.44 to 3.76), and 12 of these 
estimates were statistically significant.

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A potential limitation of this meta-analysis is that individual studies 
may have failed to control for potential known or unknown confounders. The 
most important risk factors for the development of liver cancer are 
chronic infections with hepatitis B virus and hepatitis C virus. Heavy, 
long-term alcohol consumption is also a risk factor (Yu and Yuan, 2004). 
None of the studies adjusted for hepatitis B or C virus infections, and 
only three (Calle et al, 2003; Kuriyama et al, 2005; Oh et al, 2005) 
controlled for alcohol intake. It is unlikely, however, that these risk 
factors are strongly related to body weight and entirely explain the 
observed relationship between excess body weight and liver cancer risk. 
Another limitation is that we could not examine whether the association 
between excess body weight and liver cancer was modified by hepatitis 
virus infections and alcohol intake because the studies included in this 
meta-analysis did not provide results stratified by these factors.

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As this meta-analysis was based on published studies, possible publication 
bias could have affected the results. However, neither funnel plots nor 
formal statistical tests showed evidence for publication bias.

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The observed increased risk of liver cancer associated with excess body 
weight may be mediated through the development of non-alcoholic fatty 
liver disease (NAFLD), a chronic liver disease that occurs in 
non-drinkers. NAFLD is characterized by a spectrum of liver tissue 
changes, ranging from accumulation of fat in the liver to non-alcoholic 
steatohepatitis (NASH), cirrhosis, and liver cancer at the most extreme 
end of the spectrum. Up to 90% of obese individuals have some degree of 
fatty liver, and approximately 2530% have NASH (Neuschwander-Tetri and 
Caldwell, 2003).

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In summary, this meta-analysis supports evidence of an increased risk of 
liver cancer among overweight and obese persons. These findings indicate 
that liver cancer may, in part, be prevented by maintaining a healthy body 
weight.

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ACKNOWLEDGMENTS

This work was supported by grants from the Swedish Cancer Society.

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REFERENCES

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snip

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Similar Articles in PUBMED

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