INTRODUCTION

Gallbladder cancer (GBC) is an uncommon but highly fatal malignancy; fewer than 5000 new cases are diagnosed each year in the United States. The majority are found incidentally in patients undergoing exploration for cholelithiasis; a tumor will be found in 1 to 2 percent of such cases [1-4]. The poor prognosis associated with GBC is thought to be related to advanced stage at diagnosis, which is due both to the anatomic position of the gallbladder, and the vagueness and nonspecificity of symptoms.

Here we will discuss the epidemiology, risk factors, clinical features, and diagnostic evaluation of GBC. Treatment of localized, potentially resectable GBC, and treatment for advanced disease are covered separately, as is cholangiocarcinoma. (See "Adjuvant treatment for localized, potentially resectable gallbladder cancer" and "Treatment of advanced, unresectable gallbladder cancer" and "Epidemiology, pathogenesis, and classification of cholangiocarcinoma" and "Clinical manifestations and diagnosis of cholangiocarcinoma".)

EPIDEMIOLOGY

Worldwide, there is a prominent geographic variability in GBC incidence that correlates with the prevalence of cholelithiasis. High rates of GBC are seen in South American countries, particularly Chile, Bolivia, and Ecuador, as well as some areas of India, Pakistan, Japan and Korea [5,6]. In Chile, mortality rates from GBC are the highest in the world. These populations all share a high prevalence of gallstones and/or salmonella infection, both recognized risk factors for GBC [7-9]. Both genetic factors and socioeconomic issues that delay or prevent access to cholecystectomy for gallstones are thought to be contributory [10,11]. (See 'Risk factors' below and 'Molecular pathogenesis' below.)

North America is considered a low incidence area. In the United States, GBC is the most common cancer arising in the biliary tract [1]. Estimates from the SEER (Surveillance, Epidemiology and End Results) database reveal an incidence of 1 to 2 cases per 100,000 population in the US [1]. Although the available data support a decreased overall incidence of GBC in the United States over the last 30 years, the incidence may be increasing in younger individuals [12,13]. In contrast to the general population, GBC is the most common GI malignancy in both Southwestern Native Americans and in Mexican Americans [14].

In addition to geography, there are also age, race, and gender-related differences in the incidence of GBC. Incidence steadily increases with age, women are affected two to six times more often than men [15,16], and GBC is more common in Caucasians than in blacks [17].