Two Genes Linked to Risk of Gallbladder Cancer

By performing a genome-wide scan (GWAS) of gallbladder cancer patients and hospital visitor controls, a team of researchers identified two genes that were associated with a small but definite risk of developing the disease.

Gallbladder cancer is highly lethal, with notable differences in incidence by geography and ethnic background. A team comprising investigators from Johns Hopkins University, the [U.S.] National Cancer Institute and Tata Memorial Cancer Centre performed a genome-wide scan of gallbladder cancer cases and hospital visitor controls, both of Indian descent.

To carry out the study, the investigators collected blood samples from 1,042 patients who were treated in Mumbai between September 2010 and June 2015. They also collected blood samples during this time from 1,709 healthy volunteers matched by age, sex, and geographic origin with no known cancers who were visiting patients at the hospital. Thus, the discovery cohort comprised 1042 gallbladder cancer cases and 1709 controls while a replication cohort collected in 2015 and 2016 contained 428 gallbladder cancer cases and 420 controls.

The investigators examined three of the most significant single-nucleotide polymorphisms (SNPs) in the replication cohort and did a meta-analysis of the GWAS discovery and replication sets to get combined estimates of association.

Results revealed genome-wide significant associations for several markers in the chromosomal region 7q21.12 harboring both the ABCB1 (ATP-binding cassette sub-family B member 1) and ABCB4 (ATP binding cassette subfamily B member 4) genes. These genes are known to be involved in moving lipids through the liver, gallbladder, and bile ducts, and a previous study had associated ABCB4 with the formation of gallstones, a known risk factor for gallbladder cancer.

"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," said contributing author Dr. Nilanjan Chatterjee, professor of oncology and biostatistics at John Hopkins University. "Using the latest technologies to look at the causes – notably the genetic underpinnings – of this understudied disease just makes a lot of sense."

The study was published in the March 5, 2017, online edition of the journal The Lancet Oncology.