A team of researchers from India and the US has identified several gene variants which may predispose individuals to develop gallbladder cancer.Although gallbladder cancer is rare in most parts of the world, it is far more common among some ethnic groups, such as Native Americans in North America, and in certain geographic regions, including Central and South America and East and Southeast Asia.The 178,000 new cases diagnosed worldwide each year are centered primarily in these high-risk regions."Using the latest technologies to look at the causes - notably the genetic underpinnings - of this understudied disease just makes a lot of sense," said study co-leader Nilanjan Chatterjee, Professor at Johns Hopkins University Bloomberg School of Public Health in the US.The researchers estimated that as much as 25 per cent of gallbladder cancer risk could be explained by common genetic variants."Gallbladder cancer, like many other cancers and complex diseases, is likely to be associated with many genetic markers, each of which may have small effects, but in combination they can explain substantial variation in risk," Chatterjee said.
The findings, published in the journal The Lancet Oncology, could lead to a better understanding of the causes of this highly fatal condition, which could in turn lead to better treatments for the disease.The gallbladder is a tiny organ in the abdomen which stores bile, the digestive fluid produced by the liver.When gallbladder cancer is discovered early, the chances for survival are good, but most gallbladder cancers are discovered late as it is difficult to diagnose since it often causes no specific symptoms.To search for which genes might be important in gallbladder cancer, investigators at the Tata Memorial Centre gathered blood samples from 1,042 patients who were treated at the Centre's Hospital in Mumbai between September 2010 and June 2015. The researchers also collected blood samples during this time from 1,709 healthy volunteers with no known cancers who were visiting patients at the hospital.
The researchers found highly significant association for multiple DNA variants near two genes -- ABCB4 and ABCB1 -- known to be involved in moving lipids through the liver, gallbladder and bile ducts. A previous study had associated ABCB4 with the formation of gallstones, a known risk factor for gallbladder cancer. But the new results showed for the first time that common inherited variants in this region may predispose individuals to gallbladder cancer itself, independent of gallstone status, Chatterjee said.The researchers later replicated these results using blood samples gathered from 447 more patients with gallbladder cancer and 470 healthy volunteers from Tata Memorial Hospital and Sanjay Gandhi Postgraduate Institute of Medical Science in Uttar Pradesh, India.