Abstract
ObjectiveTo investigate the association between metabolic risk factors (individually and in combination) and risk of gallbladder cancer (GBC).MethodsThe metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway, Austria, and Sweden with data on 578,700 men and women. We used Cox proportional hazard regression models to calculate relative risks of GBC by body mass index (BMI), blood pressure, and plasma levels of glucose, cholesterol, and triglycerides as continuous standardised variables and their standardised sum of metabolic syndrome (MetS) z-score. The risk estimates were corrected for random error in measurements.ResultsDuring an average follow-up of 12.0 years (SD = 7.8), 184 primary gallbladder cancers were diagnosed. Relative risk of gallbladder cancer per unit increment of z-score adjusted for age, smoking status and BMI (except for BMI itself) and stratified by birth year, sex and sub-cohorts, was for BMI 1.31 (95% confidence interval 1.11, 1.57) and blood glucose 1.76 (1.10, 2.85). Further analysis showed that the effect of BMI on GBC risk is larger among women in the premenopausal age group (1.84 (1.23, 2.78)) compared to those in the postmenopausal age group (1.29 (0.93, 1.79)). For the other metabolic factors no significant association was found (mid blood pressure 0.96 (0.71, 1.31), cholesterol 0.84 (0.66, 1.06) and serum triglycerides 1.16 (0.82, 1.64)). The relative risk per one unit increment of the MetS z-score was 1.37 (1.07, 1.73).ConclusionThis study showed that increasing BMI and impaired glucose metabolism pose a possible risk for gallbladder cancer. Beyond the individual factors, the results also showed that the metabolic syndrome as an entity presents a risk constellation for the occurrence of gallbladder cancer.
Highlights
Primary gallbladder cancer (GBC) is the most common biliary tract tumour and the sixth most common cancer affecting the gastrointestinal tract [1,2]
Most of these studies are either based on a single specific metabolic factor like obesity or diabetes [10,11,12,14], apply an unfavourable proxy for Metabolic syndrome (MetS) or they are non-prospective in nature [13,14,15,16,17]. To our knowledge this is the largest prospective study that assessed MetS and separate metabolic risk factors like serum lipids and blood pressure in association with gallbladder carcinoma. In this large study of 578,700 participants, we aimed to investigate the association between metabolic risk factors, individually and in combination, and the risk of gallbladder cancer, taking random error into account
Study Population and Measurements The study population comes from the Metabolic syndrome and Cancer project (Me-Can) which includes cohorts with 578,700 participants from Norway, Austria and Sweden
Summary
Primary gallbladder cancer (GBC) is the most common biliary tract tumour and the sixth most common cancer affecting the gastrointestinal tract [1,2]. Metabolic syndrome (MetS) is a constellation of factors related to insulin resistance including obesity, impaired glucose tolerance, dyslipidaemia and hypertension with varying definitions [5] It has consistently been associated with an increased risk of cardiovascular diseases and diabetes type 2 [6,7], and recently with risk of cancer at some sites like colorectal, prostate and liver cancers [8,9,10,11,12,13]. To our knowledge this is the largest prospective study that assessed MetS and separate metabolic risk factors like serum lipids and blood pressure in association with gallbladder carcinoma
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