Natural history of gallbladder Cancer

Principal investigator: DRA. Catterina Ferreccio
Associated researchers: Juan Carlos Roa, Sandra Cortés

The objective of this project is to provide key information to understand how it develops cancer of the gallbladder (CVB) in patients with gallstones. Proposed, documenting the evolution of the risk factors of CVB, both factors known as new, to identify early markers and potential prevention or control measures. The prospective population cohort approach allows us to simultaneously evaluate the exposure to multiple factors, analyze their occurrence in time and its relationship with different results in the gallbladder, Since chronic inflammation, metaplasia, Dysplasia, cancer in situ and invasive cancer. Chilean women have one of the highest rates of mortality by CVB reported worldwide, being the main death by cancer in women up to the year 2010. Given that is rare in developed countries, the CVB is one of the least studied cancers in the world, Despite being a highly lethal cancer for which there are no measures apart from the surgery of gallbladder - cholecystectomy - early detection and prevention. In Chile, cholecystectomy is offered primarily to people aged 35-49 years of age, presenting gallstones - cholelithiasis- symptomatic. The prevalence of cholelithiasis in Chile is 27% (13% men, 37% women), only 30% of these cases are symptomatic. On the other hand, This preventive program only covers people under 49 years of age, Although the increased risk to older (CVB in cholecystectomies is 0,5% at age 30 to 39 vs 11,0more than 70%). It is estimated that only 1% of lithiasis carriers develop CVB; However, the current approach does not focus on higher risk group. This lack of focus implies higher costs for a large number of people who would not need the operation. Our goal is to find epidemiological or molecular markers that will help identify that 1% of the population that is most at risk.

Hypothesis: The risk of developing CVB or gallbladder lesions is associated with:

1.- A unique molecular profile of inflammatory markers in the blood that differ from markers that are found in individuals with lithiasis or in people without the disease of the gallbladder.
2.- Chronic infection with Enterobacteriaceae in particular, S. typhi, S. paratyphi, Helicobacter species and others.
3.- Several native Americans markers and genetic polymorphisms.
4.- Chemical contaminants in food – aflatoxins, pesticides

Specific objectives
Measure markers of inflammation at the beginning and every 2 years to describe its dynamics and association with the evolution of vesicular disease.
Current or past biliary infection through the measurement of serum antibodies against selected agents identify and characterise the Microbiome of the subjects in the study.
Determine the family aggregation of lithiasis and CVB, We will study the genes of selected candidates and measure markers of ethnicity as well as a study of whole-genome Association (In English, GWAS (Genome-wide association study).
Assess environmental factors - agro-industrial compounds, heavy metals and mycotoxins- to which participants have been exposed throughout his life and his association with CVB.
Expected results, dissemination and transfer. This single cohort study on the natural history of the CVB will enable the identification and validation of promising biomarkers of susceptibility or early disease.