Article

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; Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. .
International Journal of Cancer (Impact Factor: 6.2). 05/2012; DOI: 10.1002/ijc.27645
Source: PubMed

ABSTRACT 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.

0 Bookmarks
 · 
150 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: It was estimated that from 2002 to 2008 the risk of developing cancer increased a quarter-fold in men and two-fold in women due to excessive BMI. Obesity, metabolic syndrome and type 2 diabetes mellitus are strictly related and are key pathogenetic factors of non-alcoholic fatty liver disease (NAFLD), the most frequent liver disease worldwide. The most important consequence of the "metabolic epidemics" is the probable rise in the incidence of hepatocarcinoma (HCC), and NAFLD is the major causative factor. Adipose tissue is not merely a storage organ where lipids are preserved as an energy source. It is an active organ with important endocrine, paracrine, and autocrine actions in addition to immune functions. Adipocytes produce a wide range of hormones, cytokines, and growth factors that can act locally in the adipose tissue microenvironment and systemically. In this article, the main roles of insulin growth factor (IGF)-1 and IGF-2 are discussed. The role of IGF-2 is not only confined to HCC, but it may also act in early hepato-carcinogenesis, as pre-neoplastic lesions express IGF-2 mRNA. IGF-1 and IGF-2 interact with specific receptors (IGF-1R and IGF-2R). IGF-1R is over-expressed in in vitro and in animal models of HCC and it was demonstrated that IGF ligands exerted their effects on HCC cells through IGF-1R and that it was involved in the degeneration of pre-neoplastic lesions via an increase in their mitotic activity. Both IGF-2R and TGF β, a growth inhibitor, levels are reduced in human HCC compared with adjacent normal liver tissues. Another key mechanism involves peroxisome proliferator-activated receptor (PPAR)γ. In in vitro studies, PPARγ inhibited various carcinomas including HCC, most probably by regulating apoptosis via the p21, p53 and p27 pathways. Finally, as a clinical consequence, to improve survival, efforts to achieve a "healthier diet" should be promoted by physicians and politicians.
    World journal of gastroenterology : WJG. 07/2014; 20(28):9217-9228.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Obesity is a complex disease that results from increased energy intake and decreased energy expenditure. The gastrointestinal system plays a key role in the pathogenesis of obesity and facilitates caloric imbalance. Changes in gastrointestinal hormones and the inhibition of mechanisms that curtail caloric intake result in weight gain. It is not clear if the gastrointestinal role in obesity is a cause or an effect of this disease. Obesity is often associated with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Obesity is also associated with gastrointestinal disorders, which are more frequent and present earlier than T2DM and CVD. Diseases such as gastroesophageal reflux disease (GERD), cholelithiasis, or nonalcoholic steatohepatitis are directly related to body weight and abdominal adiposity. Our objective is to assess the role of each gastrointestinal organ in obesity and the gastrointestinal morbidity resulting in those organs from the effects of obesity.
    Annals of the New York Academy of Sciences 03/2014; · 4.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the association between body mass index (BMI, kg/m(2)) and incidence of biliary tract disease. We performed a systematic review and a meta-analysis of prospective studies by searching the database of PubMed and EMBASE published up to December 31, 2013. Outcome of interest was disease of biliary tract system (gallbladder, extrahepatic bile duct and Ampullar of Vater). We used a random-effects model to combine the study-specific relative risks (RRs) and 95% confidence intervals (95% CIs) from 22 prospective studies. We examined whether BMI was associated with a higher risk of biliary tract disease in a combined analysis. The positive association was stronger for non-cancer biliary tract disease than biliary tract cancer; combined RRs (95% CIs) comparing the top with bottom categories were 1.40 (1.15-1.65) for biliary tract cancer and 2.75 (2.35-3.15) for non-cancer biliary tract disease (P for difference<0.001). For non-cancer biliary tract disease, combined RRs (95% CIs) comparing the top with bottom categories were 3.21 (2.48-3.93) for women and 2.01 (1.66-2.37) for men (P for difference=0.04). Obesity is associated with higher risks of biliary tract cancer and, to a greater extent, non-cancer biliary tract disease.
    Preventive Medicine 04/2014; · 3.50 Impact Factor