MEDICAL: DISEASES: CANCER : LIVER CANCER :
MEDICAL: CONDITIONS: OBESITY :
Overweight, Obesity and Risk of Liver Cancer:
A Meta-Analysis of Cohort Studies
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
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.
Keywords: body mass index, cohort studies, liver cancer, meta-analysis, obesity, review
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.
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.
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.
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.
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.
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.
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).
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.
This work was supported by grants from the Swedish Cancer Society.
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