Abdominal obesity, weight gain during adulthood and risk of liver and biliary tract cancer in a European cohort

Section of Epidemiology, Institute of Experimental Medicine, Christian-Albrechts University of Kiel, Kiel, Germany
International Journal of Cancer (Impact Factor: 5.09). 05/2012; 132(3). DOI: 10.1002/ijc.27645
Source: PubMed


General obesity has been positively associated with risk of liver and probably with biliary tract cancer, but little is known about abdominal obesity or weight gain during adulthood. We used multivariable Cox proportional hazard models to investigate associations between weight, body mass index, waist and hip circumference, waist-to-hip and waist-to-height ratio (WHtR), weight change during adulthood and risk of hepatocellular carcinoma (HCC), intrahepatic (IBDC) and extrahepatic bile duct system cancer [EBDSC including gallbladder cancer (GBC)] among 359,525 men and women in the European Prospective Investigation into Cancer and Nutrition study. Hepatitis B and C virus status was measured in a nested case-control subset. During a mean follow-up of 8.6 years, 177 cases of HCC, 58 cases of IBDC and 210 cases of EBDSC, including 76 cases of GBC, occurred. All anthropometric measures were positively associated with risk of HCC and GBC. WHtR showed the strongest association with HCC [relative risk (RR) comparing extreme tertiles 3.51, 95% confidence interval (95% CI): 2.09-5.87; p(trend) < 0.0001] and with GBC (RR: 1.56, 95% CI: 1.12-2.16 for an increment of one unit in WHtR). Weight gain during adulthood was also positively associated with HCC when comparing extreme tertiles (RR: 2.48, 95% CI: 1.49-4.13; <0.001). No statistically significant association was observed between obesity and risk of IBDC and EBDSC. Our results provide evidence of an association between obesity, particularly abdominal obesity, and risk of HCC and GBC. Our findings support public health recommendations to reduce the prevalence of obesity and weight gain in adulthood for HCC and GBC prevention in Western populations.

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    • "Most HCC occurs in the setting of viral infection, alcohol abuse, and/or nonalcoholic steatohepatitis. Therefore, the prevention of hepatitis B and C virus transmission as well as the institution of guidelines to reduce the prevalence of obesity must be the focus for HCC prevention [4,5]. Therefore, understanding the molecular mechanisms of HCC and establishing more effective therapies are critical and urgent issues. "
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    ABSTRACT: Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor in men and the seventh in women and understanding the molecular mechanisms of HCC and establishing more effective therapies are critical and urgent issues. Our objective was to study the expression of ferroportin in hepatocellular carcinoma (HCC) tissue samples and the relationship between ferroportin expression and HCC characteristics. Sixty HCC tissues and their corresponding para-cancer liver tissues (PCLT) were obtained from sixty HCC patients who had undergone hepatectomy in the Second Xiangya Hospital of Central South University. Ten normal liver tissue samples were also obtained as a control. Immunohistochemistry (IHC) was performed to analyze the ferroportin expression in HCC, and the relationship between ferroportin expression and HCC clinical pathological characteristics also was analyzed. For the evaluation of IHC results, the comprehensive scoring criteria were met according to the staining intensity and the number of positive staining cells. Western blotting was performed to detect the expression level of ferroportin in HCC cell lines. Ferroportin expression in HCC tissue was significantly lower compared to PCLT and normal liver tissue (P <0.05). Moreover, ferroportin expression was related to liver cancer cell de-differentiation, the severity degree in TNM staging, Edmondson-Steiner grading, intrahepatic metastasis and portal vein invasion. In addition, high expression of ferroportin was observed in normal human liver cell lines L02 and HL7702, whereas weak positive expression and even negative expression of ferroportin were observed in HCC cell lines FOCUS, MHCC-97H, HepG2 and SMMC-7721. Furthermore, among the four kinds of HCC cell lines, the expression level of ferroportin was the lowest in MHCC-97H cells. Ferroportin expression level declines along with the progression of liver cancer, suggesting that the reduction of ferroportin may serve as an important marker for poor HCC prognosis and as a new therapeutic target.
    12/2013; 18(1):59. DOI:10.1186/2047-783X-18-59
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    ABSTRACT: Gallbladder cancer (GBC) is a lethal and a common malignancy affecting mostly females. There are restricted high incidence pockets across the world and in northern India highest incidence of GBC is reported from the Gangetic belt. The etiology of this disease remains largely unknown though several risk factors have been stated. The genetic aberrations in GBC involving mutations in tumor suppressor genes and oncogenes have been reported in literature. However, there is scarcity of data regarding epigenetic changes that may also be involved in gallbladder carcinogenesis. This review attempts to summarize our current understanding of the epigenetic changes in GBC.
    Indian Journal of Surgical Oncology 12/2013; 4(4). DOI:10.1007/s13193-013-0240-0
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    ABSTRACT: Background The type and quantity of dietary carbohydrate as quantified by glycemic index (GI) and glycemic load (GL), and dietary fiber may influence the risk of liver and biliary tract cancers, but convincing evidence is lacking.Patients and methodsThe association between dietary GI/GL and carbohydrate intake with hepatocellular carcinoma (HCC; N = 191), intrahepatic bile duct (IBD; N = 66), and biliary tract (N = 236) cancer risk was investigated in 477 206 participants of the European Prospective Investigation into Cancer and Nutrition cohort. Dietary intake was assessed by country-specific, validated dietary questionnaires. Hazard ratios and 95% confidence intervals were estimated from proportional hazard models. HBV/HCV status was measured in a nested case-control subset.ResultsHigher dietary GI, GL, or increased intake of total carbohydrate was not associated with liver or biliary tract cancer risk. For HCC, divergent risk estimates were observed for total sugar = 1.43 (1.17-1.74) per 50 g/day, total starch = 0.70 (0.55-0.90) per 50 g/day, and total dietary fiber = 0.70 (0.52-0.93) per 10 g/day. The findings for dietary fiber were confirmed among HBV/HCV-free participants [0.48 (0.23-1.01)]. Similar associations were observed for IBD [dietary fiber = 0.59 (0.37-0.99) per 10 g/day], but not biliary tract cancer.Conclusions Findings suggest that higher consumption of dietary fiber and lower consumption of total sugars are associated with lower HCC risk. In addition, high dietary fiber intake could be associated with lower IBD cancer risk.
    Annals of Oncology 11/2012; 24(2). DOI:10.1093/annonc/mds434 · 7.04 Impact Factor
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