Biliary tract cancer and stones in relation to chronic liver conditions: A population-based study in Shanghai, China.
ABSTRACT Biliary tract cancers are relatively rare but fatal tumors. Apart from a close link with gallstones and cholangitis, risk factors for biliary tract cancer are obscure. Chronic liver conditions, including liver cirrhosis, have been linked to a higher risk of biliary tract cancer. In a population-based case-control study conducted in Shanghai, China, we investigated the relationships of a history of chronic hepatitis and liver cirrhosis as well as a family history of liver cancer with biliary tract cancer risk. The study included 627 patients with biliary tract cancers (368 gallbladder, 191 bile duct and 68 ampulla of Vater), 1,037 patients with biliary stones (774 gallbladder stones and 263 bile duct stones) and 959 healthy subjects randomly selected from the population. Bile duct cancer was associated with self-reports of chronic liver conditions, including a history of chronic hepatitis (OR = 2.0, 95% CI 0.9-4.4), liver cirrhosis (OR = 4.7, 95% CI 1.9-11.7) and a family history of primary liver cancer (OR = 2.0, 95% CI 1.0-3.9). The excess risk persisted after adjustment for gallstones and were more pronounced among subjects without gallstones (OR = 5.0, 95% CI 1.3-20.0 and OR = 4.9, 95% 2.0-12.2, respectively). History of liver conditions was also associated with an excess of biliary stones (OR = 1.9, 95% CI 1.2-3.0). No association was found for cancers of the gallbladder and ampulla of Vater. A history of chronic hepatitis and cirrhosis may be risk factors for extraheptic bile duct cancer. Given that chronic infection with hepatitis B virus (HBV) is the most common cause of liver disease in China, serologic markers of HBV need to be measured in future studies to examine the link between HBV and bile duct cancer.
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ABSTRACT: Gallstone disease (GD) is a chronic recurrent hepatobiliary disease, the basis for which is the impaired metabolism of cholesterol, bilirubin and bile acids, which is characterized by the formation of gallstones in the hepatic bile duct, common bile duct, or gallbladder. GD is one of the most prevalent gastrointestinal diseases with a substantial burden to health care systems. GD can result in serious outcomes, such as acute gallstone pancreatitis and gallbladder cancer. The epidemiology, pathogenesis and treatment of GD are discussed in this review. The prevalence of GD varies widely by region. The prevalence of gallstone disease has increased in recent years. This is connected with a change in lifestyle: reduction of motor activity, reduction of the physical load and changes to diets. One of the important benefits of early screening for gallstone disease is that ultrasonography can detect asymptomatic cases, which results in early treatment and the prevention of serious outcomes. The pathogenesis of GD is suggested to be multifactorial and probably develops from complex interactions between many genetic and environmental factors. It suggests that corticosteroids and oral contraceptives, which contain hormones related to steroid hormones, may be regarded as a model system of cholelithiasis development in man. The achievement in the study of the physiology of bile formation and the pathogenesis of GD has allowed expanding indications for therapeutic treatment of GD.World journal of hepatology. 02/2012; 4(2):18-34.
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ABSTRACT: BACKGROUND AND AIM: Altered motility of the gallbladder is associated with an increased risk of gallstones and can result in biliary tract cancers. Cholecystokinin (CCK) is an important modulator of gallbladder motility which functions by activating CCK type-A receptor (CCKAR). The aim of this study was to determine whether genetic variants in CCK and CCKAR are associated with the risk of biliary tract cancers and stones. METHODS: We investigated the associations between 9 single nucleotide polymorphisms (SNPs) in CCK and CCKAR in a population-based case-control study, including 439 biliary tract cancer cases (253 gallbladder, 133 extrahepatic bile duct and 53 ampulla of Vater cancer cases), 429 biliary stone cases, and 447 population controls in Shanghai, China. Results We found that women with the CCKAR rs1800855 AA genotype had an increased risk of gallbladder cancer (odd ratio (OR) =2.37, 95% confidence interval (CI): 1.36-4.14) compared to subjects with the TT genotype, and remained significant after Bonferroni correction (P=0.0056). Additionally, female carriers of the CCKAR haplotype C-T-C-T (rs2071011-rs915889-rs3822222-rs1800855) had a reduced risk of gallbladder cancer (OR=0.61, 95%CI: 0.43-0.86) compared to those with the G-C-C-A haplotype, the association also remained significant after Bonferroni correction. CONCLUSIONS: These findings suggest that variants in the CCKAR gene may influence the risk of gallbladder cancer in women. Additional studies are needed to confirm our findings.Journal of Gastroenterology and Hepatology 05/2013; · 3.33 Impact Factor
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ABSTRACT: BACKGROUND: Genetic variants in inflammation-related genes have been associated with biliary stones and biliary tract cancers in previous studies. METHODS: To follow-up on these findings, we examined 35 single nucleotide polymorphism (SNPs) in 5 genes related to inflammation (IL8, NFKBIL, RNASEL, TNF, and VEGFA) in 456 participants with incident biliary tract cancer cases (262 gallbladder, 141 extrahepatic bile duct, 53 ampulla of Vater), 982 participants with biliary stones, and 860 healthy controls in a population--based case--control study in Shanghai, China. RESULTS: Suggestive associations were observed for SNPs in VEGFA with biliary stones, IL8 with gallbladder and ampulla of Vater cancers, and RNASEL with ampulla of Vater cancer (false discovery rate<=0.2). CONCLUSION: These findings provide additional support for the role of inflammation in biliary stones and biliary tract cancer risk and need further validation.BMC Cancer 10/2012; 12(1):468. · 3.33 Impact Factor