While some diseases are universal, affecting people similarly no matter their genetic background, others are linked to certain ancestries. Take for example extranodal natural killer T-cell lymphoma (NKTCL), an extremely aggressive cancer limited almost exclusively to East Asian and Latin American populations, and which seldom occurs in those of European ancestry.
NKTCL is a baffling disease that originates in the nasal cavity before quickly spreading to other tissues. Apart from its unique epidemiological distribution, Epstein-Barr virus (EBV) infection has also been flagged as a significant contributing factor.
Despite the disproportionate impact of NKTCL on Asian communities, people of Asian descent are considerably underrepresented in published genetic studies on the topic, making it difficult for experts to draw clear lines around the genes that contribute to an increased risk for NKTCL.
The many unanswered questions surrounding NKTCL’s origins have spurred an in-depth genome-wide association study published in The Lancet Oncology that focused entirely on East Asian populations—the largest of its kind to date.
An international team of researchers and physicians from countries including China, Hong Kong, South Korea, Singapore and Malaysia came together to find novel distinguishing genetic patterns tied to NKTCL development. Over 1,400 NKTCL patients and 20,000 controls were recruited from 11 centers across East Asia.
Among the study’s authors were Chiea Chuen Khor, a Senior Principal Investigator from A*STAR's Genome Institute of Singapore (GIS), and Soo-Yong Tan, a Senior Principal Investigator at A*STAR’s Institute of Molecular and Cell Biology (IMCB).
“We know that cancers that associate with EBV may have a strong genetic predisposition,” Khor said. “To be sure, we designed a well-powered initial genome-wide scan, followed by validation testing in three additional independent collections.”
Using a suite of bioinformatics approaches, the research team identified two chromosomal regions called IL18RAP and HLA-DRB1 that control immune cell activation following infections and also play a part in the genesis of NKTCL.
“The findings tell us that NKTCL is a highly immune tumor,” said Khor. “To treat it, we have to harness the immune response appropriately.” With these new findings, cancer immunotherapies may someday replace the current gold standard of care for NKTCL, chemotherapy and radiotherapy, both of which are associated with a low five-year survival rate.
The study also highlights the importance of ethnic diversity in genetic studies, paving the way for more population-specific investigations into the relationships between our genes and cancer.
“It is critical that we conduct population-specific genetic analyses to delineate the genetic component of cancer development, as different cancers have different preponderances in different populations,” Khor said.