Modern perspectives on factors predisposing to the development of gallbladder cancer.

BACKGROUND: Gallbladder cancer (GBC) is a rare malignancy, yet certain groups are at higher risk. Knowledge of predisposing factors may facilitate earlier diagnosis by enabling targeted investigations into otherwise non-specific presenting signs and symptoms. Detecting GBC in its initial stages offers patients their best chance of cure.

METHODS: PubMed was searched for recent articles (2008-2012) on the topic of risk factors for GBC. Of 1490 initial entries, 32 manuscripts reporting on risk factors for GBC were included in this review.

RESULTS: New molecular perspectives on cholesterol cycling, hormonal factors and bacterial infection provide fresh insights into the established risk factors of gallstones, female gender and geographic locality. The significance of polyps in predisposing to GBC is probably overstated given the known dysplasia-carcinoma and adenoma-carcinoma sequences active in this disease. Bacteria such as Salmonella species may contribute to regional variations in disease prevalence and might represent powerful targets of therapy to reduce incidences in high-risk areas. Traditional risk factors such as porcelain gallbladder, Mirizzi's syndrome and bile reflux remain important as predisposing factors.

CONCLUSIONS: Subcentimetre gallbladder polyps rarely become cancerous. Because gallbladder wall thickening is often the first sign of malignancy, all gallbladder imaging should be scrutinized carefully for this feature.