Tumori, 96: 911-917, 2010
Risk factors for hepatocellular carcinoma: a case-control study in Belgrade (Serbia) Milena Kanazir1, Ivan Boricic2, Dragan Delic3, Darija Kisic Tepavcevic4, Aleksandra Knezevic5, Tanja Jovanovic5, and Tatjana Pekmezovic4 1
Institute of Public Health of Serbia, Belgrade; 2Institute of Pathology, School of Medicine, Belgrade; Institute of Infectious and Tropical Diseases, Clinical Center of Serbia, Belgrade; 4 Institute of Epidemiology, School of Medicine, Belgrade; 5Institute of Microbiology and Immunology, School of Medicine, Belgrade, Serbia 3
ABSTRACT
Aims and background. The objective of this case-control study was to test the existing hypotheses about factors related to the occurrence of hepatocellular carcinoma in the population of Belgrade (Serbia). Methods and study design. The investigation was conducted between 2004 and 2007 and consisted of 45 newly diagnosed, histologically confirmed hepatocellular carcinoma patients and 90 individually gender- and age-matched hospital controls. Conditional univariate and multivariate logistic regression analyses were applied. Results. A highly statistically significant association (P = 0.001) was demonstrated between hepatocellular carcinoma and HBsAg positivity and the presence of hepatitis C virus antibodies. Diabetes mellitus was significantly (P = 0.018) associated with an increased risk of hepatocellular carcinoma. A statistically significant inverse association was shown between low parity and the risk of hepatocellular carcinoma (P = 0.033). The risk increased significantly with a longer history of cigarette smoking (P = 0.044), as well as the daily consumption of hard liquor (P = 0.049). A weekly intake of fish (P = 0.003) and yogurt (P = 0.003) and daily intake of boiled vegetables (P = 0.001) were reported more frequently by controls than hepatocellular carcinoma cases. In the current study, a high intake of salty food also significantly increased the risk of hepatocellular carcinoma (P = 0.027). Based on multivariate analysis, the presence of hepatitis C virus antibodies (OR = 24.6, P = 0.001) and duration of smoking ≥25 years (OR = 3.8, P = 0.020) were significantly related to hepatocellular carcinoma, whereas the daily consumption of boiled vegetables (OR = 0.1, P = 0.011) was inversely associated with the risk of hepatocellular carcinoma. Conclusions. The findings obtained in the current study support the hypotheses that non-viral factors, such as lifestyle factors, reproductive factors, and a history of diabetes, might be involved in the etiology of hepatocellular carcinoma. Free full text available at www.tumorionline.it Key words: case-control study, hepatocellular carcinoma, risk factors.
Introduction Hepatocellular carcinoma (HCC) is a common malignant disease in many regions of the world. HCC is the fifth most common cancer and the third most common cause of cancer-related deaths worldwide1. HCC exhibits dynamic temporal trends and evident variations among geographic areas. Therefore, the burden of HCC is not distributed uniformly throughout the world. Serbia is located in southeastern Europe and is situated in the low-medium risk zone for HCC2. The geographic distribution of HCC and the pattern of its occurrence in migrant populations indicate that this type of cancer is caused, in most cases, by environmental factors. Furthermore, epidemiologic studies have shown effects of lifestyle-related factors on the risk of HCC3-8. Many risk factors for HCC have been described, including liver cirrhosis, chronic infection with hepatitis B and/or C viruses, aflatoxin B exposure, alcohol drinking,
Acknowledgments: The work was supported by a grant from the Ministry of Science of the Republic of Serbia (grant No. 145045). Correspondence to: Tatjana Pekmezovic, Institute of Epidemiology, School of Medicine, Visegradska 26A, Belgrade 11000, Serbia. Tel/fax +381-11-3607-062; e-mail
[email protected] Received March 30, 2009; accepted March 1, 2010.
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and cigarette smoking. Overall, 80% of cases of HCC are attributable to chronic viral infections with either hepatitis B (HBV) and/or hepatitis C virus (HCV). HBV infection is the main risk factor for HCC in Asia and Africa, whereas HCV infection in Western countries and Japan has a key role in the development of HCC1. However, other factors, including diet, may be relevant, but the evidence is still unclear, except for aflatoxin B contamination8. The aim of this case-control study was to determine the risk factors for HCC in the population of Belgrade (Serbia).
Materials and methods The current study was conducted in Belgrade between 2004 and 2007. The study group consisted of 45 consecutive patients diagnosed with HCC and histologically confirmed in the Department of Gastroenterology of the Institute of Infectious Diseases and the Institute of Gastroenterology at the Clinical Center of Serbia, Belgrade, during the period between 2004 and 2007. These Institutes are the national reference centers for HCC, and virtually all patients with HCC from Belgrade are diagnosed and treated at one of these Institutes. The patients were
