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From India, first evidence of common genetic variation associated with gallbladder cancer risk

, by DCEG Staff

In the first-ever large genome-wide association study (GWAS) of gallbladder cancer, researchers have identified common genetic changes associated with elevated risk of the often fatal malignancy. Investigators from the National Cancer Institute, Division of Cancer Epidemiology and Genetics (NCI/DCEG) collaborated with colleagues at the Centre for Cancer Epidemiology and the Tata Memorial Centre, Mumbai, India, to perform this analysis, which was published March 5th in The Lancet Oncology.

The global prevalence of gallbladder cancer varies widely; certain geographic regions of India have particularly elevated rates, which makes it a prime location for such a study. Prior epidemiological studies have identified few risk factors other than history of gallstones; investigation of genetic factors has been limited. This study is the first large-scale effort to identify common single-nucleotide polymorphisms (SNPs), individual base-pair changes in DNA, that may increase an individual’s risk. The initial GWAS included over 1000 gallbladder cancer cases and 1700 controls, followed by a replication study set of roughly 430 cases and 420 controls.

Researchers found associations between higher gallbladder cancer risk and several SNPs in the gene region harboring the ABCB4 and ABCB1 genes, which are responsible for making proteins that help move a certain class of lipids from the liver to the gallbladder, suggesting a possible role for disruption of transport protein function in gallbladder cancer etiology. The authors indicate that future studies are needed to explore the complexity and mechanics of these relationships and to identify more risk-associated SNPs.

The study was co-led by Preetha Rajaraman, Ph.D., NCI Center for Global Health, and DCEG special volunteer, and Rajesh Dikshit, Ph.D., of the Tata Memorial Centre. Other collaborators included Stephen J. Chanock, M.D., Charles Chung, and former DCEG researchers Nilanjan Chatterjee, Ph.D. (co-lead), and Zhaoming Wang, Ph.D.

Reference: Mhatre, S et al. Common genetic variation and risk of gallbladder cancer in India: a case-control genome-wide association study. The Lancet Oncology. March 5, 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30167-5

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