Research ArticleMediterranean diet and hepatocellular carcinoma
Introduction
Hepatocellular carcinoma (HCC) is the most common histological type of primary liver cancer. The predominant role of chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in the aetiology of HCC is well documented [1]. Several other risk factors for HCC have been identified, including heavy alcohol intake, tobacco smoking, and obesity [2].
With the exception of aflatoxins, data on the role of diet on liver cancer are inconclusive. Some studies have shown a weak inverse association between fruit consumption and liver cancer risk, and a positive one with glycaemic load, but evidence is sparse and inconsistent [3], [4].
It has been reported that for certain diseases, notably coronary heart disease, no food, food group, or nutrient has been implicated as causal, but the evidence for a favorable role of the Mediterranean dietary pattern is convincing [5]. Data are much scantier on Mediterranean diet and cancer risk [6], [7], [8], [9]. Because HCC is a disease with a very poor prognosis, with a 5-year survival rate of less than 10% [10], any effort to identify additional modifiable causes of liver cancer would be important in order to allow a more effective prevention of the disease.
We have therefore evaluated the association between the Mediterranean dietary pattern and liver cancer by combining two large case-control studies undertaken in Italy and Greece, two countries in which the traditional Mediterranean diet is still prevalent. Age-standardized mortality from primary liver cancer (mainly HCC) is around 3/100,000 population in these countries [11]. Thus, despite being more common than in most other high income countries, HCC is still a rare disease, with a lifelong cumulative incidence around 1% in the general population.
Section snippets
Selection of cases and controls
The present data are derived from case-control studies of HCC in two Mediterranean countries.
The first study was conducted between 1999 and 2002, in the province of Pordenone (north-eastern Italy) and in the city of Naples (southern Italy) [12]. Cases were 258 patients under the age of 85 years with incident (newly diagnosed) HCC. Of the HCC cases, 29 cases did not provide a blood sample and 44 did not provide data on dietary habits, thus leaving 185 eligible cases for the present analysis. The
Results
Table 1 presents the main characteristics of cases and controls in the Italian and Greek studies, separately, for descriptive purposes. The prevalence of current smokers is higher in the Greek study than in the Italian one; 80% of cases and 11% of controls in the Italian study and 75% of cases and 4% of controls in the Greek study had serological evidence of chronic infection with HBV and/or HCV.
With regard to the main recognized HCC risk factors, after mutual adjustment, the ORs were 1.33 (95%
Discussion
Combining two large studies carried out in the Mediterranean region, we found that the degree of adherence to Mediterranean diet is significantly inversely related to HCC risk in a roughly monotonic way, so that the MDS ⩾5 was associated with an about 50% reduction in HCC incidence in comparison to MDS of 3 or less. We also found that there is evidence, albeit statistically non-significant, of super additivity in the risk implications of joint chronic hepatitis B and/or C infection and poor
Financial support
This work was supported by the contribution of the Italian Association for Cancer Research (Grant N. 10068), and the Kapodistrias program of the University of Athens, Greece. F.T. was supported by a fellowship from the Italian Foundation for Cancer Research (FIRC), and F.B. by a fellowship of the Fondazione Umberto Veronesi.
Conflict of interest
The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
Acknowledgments
The authors thank Ms. Garimoldi for editorial assistance.
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Carlo La Vecchia and Pagona Lagiou share senior co-authorship.