Metabolic syndrome and insulin resistance in relation to biliary tract cancer and stone risks: a population-based study in Shanghai, China.

BACKGROUND: Serum lipids, diabetes, and obesity, individual components of metabolic syndrome, are associated with biliary tract cancer and stone risk, but the associations of metabolic syndrome or insulin resistance with biliary tract cancers and stones are not well studied. METHODS: In this population-based case-control study in Shanghai, China (627 biliary tract cancers, 1037 biliary stones, and 959 controls), metabolic syndrome was defined as the presence of any three of the five components, including high waist circumference, high triglycerides, low high-density lipoprotein cholesterol (HDL), high blood pressure, and diabetes. Insulin resistance and ß-cell function were assessed, using homeostasis assessment models. RESULTS: Metabolic syndrome was significantly associated with gallbladder cancer (odds ratio (OR)=2.75, 95% confidence interval (95% CI)=1.82-4.15) and biliary stones (OR=1.64, 95% CI=1.24-2.16), with a significant dose effect with increasing number of metabolic syndrome components (P trend <0.0001). The observed association persisted among subjects without a history of diabetes. The association between insulin resistance and gallbladder cancer was borderline (P trend=0.06). There was a significant inverse association between ß-cell function and gallbladder cancer risk (P trend <0.001). CONCLUSION: Our findings suggest that metabolic syndrome and insulin resistance have a role in the aetiology of biliary tract cancers and biliary stones, and if confirmed, they imply that lifestyle control of these factors may lower the risk of biliary stones and biliary tract cancer.

Diabetes in relation to biliary tract cancer and stones: a population-based study in Shanghai, China.

BACKGROUND: Biliary tract cancers are rare but fatal malignancies. Diabetes has been related to biliary stones, but its association with biliary tract cancers is less conclusive. METHODS: In a population-based case-control study of 627 cancers, 1037 stones, and 959 controls in Shanghai, China, we examined the association between diabetes and the risks of biliary tract cancer and stones, as well as the effect of potential mediating factors, including serum lipids and biliary stones (for cancer), contributing to the causal pathway from diabetes to biliary diseases. RESULTS: Independent of body mass index (BMI), diabetes was significantly associated with gallbladder cancer and biliary stones ((odds ratio (OR) (95% confidence interval)=2.6 (1.5-4.7) and 2.0 (1.2-3.3), respectively). Biliary stones and low serum levels of high-density lipoprotein (HDL) were significant mediators of the diabetes effect on gallbladder cancer risk, accounting for 60 and 17% of the diabetes effect, respectively. High-density lipoprotein was also a significant mediator of the diabetes effect on biliary stones, accounting for 18% of the diabetes effect. CONCLUSIONS: Independent of BMI, diabetes is a risk factor for gallbladder cancer, but its effect is mediated in part by biliary stones and serum HDL levels, suggesting that gallbladder cancer risk may be reduced by controlling diabetes, stones, and HDL levels.

Reproductive factors and risks of biliary tract cancers and stones: a population-based study in Shanghai, China.

BACKGROUND: Parity has been linked to gallbladder cancer and gallstones, but the effects of other reproductive factors are less clear. METHODS: We examined 361 incident biliary tract cancer cases, 647 biliary stone cases, and 586 healthy women in a population-based study in Shanghai. RESULTS: The effects of parity (odds ratios, OR(> or =3 vs 1 child)=2.0, 95% confidence interval (CI) 0.7-5.1), younger age at first birth (OR(per 1-year decrease)=1.2, 95% CI 0.99-1.6), and older age at menarche (OR(per 1-year increase)=1.4, 95% CI 1.1-1.8) on gallbladder cancer risk were more pronounced among women with stones, but the interactions were not significant. CONCLUSION: Our results provide support for high parity, younger age at first birth, and late age at menarche in the development of gallbladder cancer, particularly among women with biliary stones.

Body size and the risk of biliary tract cancer: a population-based study in China.

Though obesity is an established risk factor for gall bladder cancer, its role in cancers of the extrahepatic bile ducts and ampulla of Vater is less clear, as also is the role of abdominal obesity. In a population-based case-control study of biliary tract cancer in Shanghai, China, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for biliary tract cancer in relation to anthropometric measures, including body mass index (BMI) at various ages and waist-to-hip ratio (WHR), adjusting for age, sex, and education. The study included 627 patients with biliary tract cancer (368 gall bladder, 191 bile duct, 68 ampulla of Vater) and 959 healthy subjects randomly selected from the population. A higher BMI at all ages, including early adulthood (ages 20-29 years), and a greater WHR were associated with an increased risk of gall bladder cancer. A high usual adult BMI (>or=25) was associated with a 1.6-fold risk of gall bladder cancer (95% CI 1.2-2.1, P for trend <0.001). Among subjects without gallstones, BMI was also positively associated with gall bladder cancer risk. Regardless of BMI levels, increasing WHR was associated with an excess risk of gall bladder cancer risk, with those having a high BMI (>or=25) and a high WHR (>0.90) having the highest risk of gall bladder cancer (OR=12.6, 95% CI 4.8-33.2), relative to those with a low BMI and WHR. We found no clear risk patterns for cancers of the bile duct and ampulla of Vater. These results suggest that both overall and abdominal obesity, including obesity in early adulthood, are associated with an increased risk of gall bladder cancer. The increasing prevalence of obesity and cholesterol stones in Shanghai seems at least partly responsible for the rising incidence of gall bladder cancer in Shanghai.

[The possibility of prediction of cholesterol saturation of gallbladder bile].

Using stepwise regression we studied the possibility to determine the cholesterol saturation index (CSI) of gallbladder bile from analysis of fasting serum bile acid, 24 hour urine bile acid or serum lipids (cholesterol and triglyceride) in 31 gallstone patients. Two multiple regression equations were obtained to predict the CSI of bile from fasting serum bile acid compositions based on absolute concentration and relative concentration. The CSI of the gallbladder bile could not be predicted from 24 hour bile acid or serum lipids. Four critical values were calculated from regression equations, which predicted the CSI of bile with the efficiency above 70 percent. This study indicated for the first time that the prediction of CSI of gallbladder bile can be obtained from an analysis of fasting serum bile acid and hence it is possible to prevent gallstone formation at the stage of cholesterol supersaturated bile production.

Gallstones and the risk of biliary tract cancer: a population-based study in China.

We conducted a population-based study of 627 patients with biliary tract cancers (368 of gallbladder, 191 bile duct, and 68 ampulla of Vater), 1037 with biliary stones, and 959 healthy controls randomly selected from the Shanghai population, all personally interviewed. Gallstone status was based on information from self-reports, imaging procedures, surgical notes, and medical records. Among controls, a transabdominal ultrasound was performed to detect asymptomatic gallstones. Gallstones removed from cancer cases and gallstone patients were classified by size, weight, colour, pattern, and content of cholesterol, bilirubin, and bile acids. Of the cancer patients, 69% had gallstones compared with 23% of the population controls. Compared with subjects without gallstones, odds ratios associated with gallstones were 23.8 (95% confidence interval (CI), 17.0-33.4), 8.0 (95% CI 5.6-11.4), and 4.2 (95% CI 2.5-7.0) for cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, respectively, persisting when restricted to those with gallstones at least 10 years prior to cancer. Biliary cancer risks were higher among subjects with both gallstones and self-reported cholecystitis, particularly for gallbladder cancer (OR=34.3, 95% CI 19.9-59.2). Subjects with bile duct cancer were more likely to have pigment stones, and with gallbladder cancer to have cholesterol stones (P<0.001). Gallstone weight in gallbladder cancer was significantly higher than in gallstone patients (4.9 vs 2.8 grams; P=0.001). We estimate that in Shanghai 80% (95% CI 75-84%), 59% (56-61%), and 41% (29-59%) of gallbladder, bile duct, and ampulla of Vater cancers, respectively, could be attributed to gallstones.