Diagnosis of pernicious anemia and the risk of pancreatic cancer.

OBJECTIVES: A number of studies have demonstrated a trophic effect of gastrin on pancreatic cancer cells in vitro. Pernicious anemia (PA) is a clinical condition characterized by chronic hypergastrinemia. The aim of this study was to determine if PA is a risk factor for pancreatic cancer. METHODS: This study is a retrospective cohort study using The Health Improvement Network database, which contains comprehensive health information on 7.5 million patients in the United Kingdom from 1993 to 2009. All patients with PA in the study cohort were identified and composed of the exposed group. Each exposed patient was matched on practice site, sex, and age with up to 4 unexposed patients without PA. The outcome was incident pancreatic cancer. The hazard ratio and 95% confidence intervals were estimated using multivariable Cox regression analysis. RESULTS: We identified 15,324 patients with PA and 55,094 unexposed patients. Mean follow-up time was similar between groups (exposed 4.31 [SD, 3.38] years, unexposed 4.63 [SD, 3.44] years). The multivariable adjusted hazard ratio for pancreatic cancer associated with PA was 1.16 (95% confidence interval, 0.77-1.76; P = 0.47). CONCLUSIONS: There is no significant association between PA and the risk of pancreatic cancer.

Incidence of bladder cancer in patients with type 2 diabetes treated with metformin or sulfonylureas.

OBJECTIVE: Previous studies evaluating the effect of metformin on cancer risk have been impacted by time-related biases. To avoid these biases, we examined the incidence of bladder cancer in new users of metformin and sulfonylureas (SUs). RESEARCH DESIGN AND METHODS: This cohort study included 87,600 patients with type 2 diabetes in The Health Improvement Network database. Use of metformin or an SU was treated as a time-dependent variable. Cox regression-generated hazard ratios (HRs) compared metformin use with SU use, adjusted for age, sex, smoking, obesity, and HbA1c level. RESULTS: We identified 196 incident bladder cancers in the metformin cohort and 66 cancers in the SU cohort. Use of metformin was not associated with decreased bladder cancer risk (HR 0.81 [95% CI 0.60-1.09]). This association did not differ by sex (P for interaction = 0.20). We observed no association with duration of metformin relative to SU use (3 to <4 years of use: 0.57 [0.25-1.34]; 4 to <5 years of use: 0.93 [0.30-2.85; ≥5 years of use: 1.18 [0.44-3.19]; P for trend = 0.26). CONCLUSIONS: Use of metformin is not associated with a decreased incidence of bladder cancer. Similar methods should be used to study other cancers that have previously been identified as potentially preventable with metformin.

Metformin and survival in pancreatic cancer: a retrospective cohort study.

OBJECTIVES: Our aim was to determine the effect of metformin exposure on survival in patients with advanced pancreatic adenocarcinoma (PAC). METHODS: A retrospective cohort study was conducted using The Health Improvement Network, a primary care electronic medical record database from the United Kingdom (2003-2010). The study cohort included all subjects with a diagnostic code for incident PAC and a preexisting diagnosis of type 2 diabetes mellitus. Subjects were classified as exposed if they were prescribed metformin around the time of PAC diagnosis (between 6 months prior and 1 month after). A secondary analysis was performed only on exposed subjects without prior (ie, 6 months before PAC diagnosis) exposure to metformin. The primary outcome was overall survival. The analysis was performed using univariate and multivariable Cox proportional hazards models. RESULTS: The study included 516 subjects with preexisting type 2 diabetes mellitus and PAC, 247 of which were exposed to metformin. In univariate and multivariable analysis, there was no difference in survival between those exposed and those unexposed to metformin in the primary analysis (hazards ratio, 1.11 [0.89-1.38], P = 0.367) or the secondary analysis (hazards ratio, 1.09 [0.80-1.47], P = 0.585). CONCLUSIONS: Metformin use is not associated with improved survival in subjects with advanced PAC.