A Randomized Double-Blind, Placebo-Controlled Multicenter 26-Week Study on the Effects of Dexlansoprazole and Esomeprazole on Bone Homeostasis in Healthy Postmenopausal Women

Background The incidence of hepatobiliary cancer is steadily increasing. The age standardized incidence rate of liver cancers has increased by 224% for males and 227% for females over the last few decades with similar trends in the incidence of bile duct and gall bladder cancers. It is unclear if this rise is related to increasing trends in in obesity, metabolic syndrome and lifestyle changes. The current evidence base is unclear. Aim To determine the association between obesity, metabolic syndrome and hepatobiliary cancers using UK primary care data. Methods A nested case-control study was performed using the THIN (The Health Improvement Network) database in the UK. Read codes were used to capture patients with a diagnosis of liver, bile duct and gall bladder cancers and these patients were matched in a 1:2 fashion with controls without a diagnosis of cancer by age, GP practice and gender, with at least one year of follow up on the database. Data on co-morbidities, events (GP or hospital visits), drug history, anthropometric data (weight, log-transformed-body mass index (BMI), blood pressure, cholesterol and glucose levels) and data on smoking and alcohol consumption was extracted from the database and analyzed in an analytical model for potential associations between hepatobiliary cancer and obesity / metabolic syndrome. Results 4287 patients (62% male, 38% female) with hepatobiliary cancers were matched with 8574 controls. On univariate analysis, age (0.99 (0.98-0.99), p<0.001), log BMI (3.223 (2.58-4.03), p<0.001), smoking (38.62 (31.47-47.4), p<0.001), diabetes (2.12 (1.94-2.31), p<0.001) and ischemic heart disease (IHD) (2.06 (1.85-2.29), p<0.001) were associated with hepatobiliary cancer. Interestingly, statin use (0.71 (0.65-0.78), p<0.001) had a negative association with hepatobiliary cancer and PPI use (3.36 (3.09-3.65), p<0.001) had a positive association. On step-wise forward conditional logistic regression, age (0.98 (0.977-0.98), p<0.001), smoking (34.58, (28.09-42.57), p<0.001), diabetes (2.28 (2.05-2.53), p<0.001), IHD (1.36 (1.2-1.54), p<0.001), PPI use (2.97 (2.71-3.26), p<0.001) and statin use (0.52 (0.47-0.58), p<0.001) were associated with the risk of hepatobiliary cancers. On modelling log BMI, diabetes and hypertension as a single covariate, there was a significant association with hepatobiliary cancer (1.59 (1,49-1.69), p<0.001), which remained significant when