Gene variants in ABCB1/ABCB4 region confer gallbladder cancer risk

An in-depth genetic analysis of people with or without gallbladder cancer by researchers at the National Institutes of Health (NIH) points to several gene variants that may explain why some people are susceptible to the disease.

Gallbladder cancer is a multifactorial disease involving combinations of multiple genetic variants. The disease is relatively rare, but in certain countries and regions of the world, its incidence is much higher. In fact, there are significant differences in incidence by geography and ethnic background. For example, Native Americans in North America are more likely than other ethnic groups to develop gallbladder cancer.

The aim of this study is to identify genetic variants that could increase the risk of gallbladder cancer. Along with colleagues in India, the NIH researchers conducted a case-control genome-wide association study of 1,042 gallbladder cancer patients and 1,709 healthy controls, both of Indian descent. Study co-leader Preetha Rajaraman and colleagues collected blood samples from these participants and used several advanced technologies to examine the samples. They identified genome-wide significant associations for several DNA variants in the chromosomal region harboring the ABCB1 and ABCB4 genes.

The two genes, ABCB1 and ABCB4, are involved in the transport of lipids through the liver, gallbladder and bile ducts. Earlier studies have suggested that defective ABCB4 leads to reduced lecithin secretion and stone formation. Gallstone is considered a risk factor for gallbladder cancer. Although people with gallstones rarely develop gallbladder cancer, more than three-quarters of patients with gallbladder cancer have gallstones when diagnosed.

This study, which has been published in Lancet Oncology, provides the first evidence that common gene variants in the ABCB1/ ABCB4 region may confer gallbladder cancer risk, regardless of whether or not a person has gallstones. Gallbladder cancer is highly lethal in part because the disease is discovered at its late stages. The findings of this study may extend the understanding of gallbladder cancer and help to develop better treatments.
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