New Genetic Changes Associated with Pancreatic Cancer Risk

The largest genome-wide association study of pancreatic cancer recently uncovered alterations to 5 genes that may increase the risk of developing the disease.
The new findings published in Nature Communications mark a significant step towards fully outlining the genetic changes that cause pancreatic cancer, according to the study authors.
They added that this study is significant because a clearer picture of how pancreatic cancer develops can result in more targeted therapies and better strategies for early detection.
The researchers previously discovered 17 variants in 13 regions.
In the current study, the authors analyzed genetic information from 11.3 million variants in 21,536 people, both with and without pancreatic cancer.
The authors discovered genetic variants on human chromosomes 1 (position 1p36.33), 7 (position 7p12), 8 (position 8q21.11), 17 (position 17q12), and 18 (position 18q21.32). These alterations may increase the risk of pancreatic cancer by 15% to 25% per copy present, according to the study.
“On an individual level, having 1 of these variants isn’t very predictive of cancer, in that they’re only associated with a modest change in risk, but when taken together, they help to create the fuller picture of how pancreatic cancer develops,” said lead researcher Alison Klein, PhD, MHS.
One of the variants discovered was in the NOC2L protein, which binds to the p53 tumor suppressor protein and p63 tumor suppressor genes. Both p53 and p63 are known to increase the risk of pancreatic cancer, according to the study.
HNF4G and HNF1B gene variants have been observed to regulate the pancreas and may be involved with the development of cancer, according to the authors. Variation in HNF1B hepatocyte growth factor has also been associated with mature onset of diabetes that typically only affects younger individuals.
Other variants were discovered near the GRP gene, which releases gastrointestinal hormones, and on TNS3, a gene that regulates cell adhesion and migration, according to the study.
Although pancreatic cancer is relatively rare, it can be particularly aggressive and better treatments are needed, according to the study. The researchers said that large-scale research collaborations are needed to conduct studies that include more patients.  
In future studies, the authors said they plan to dive deeper into other genes potentially involved with pancreatic cancer.
“There is still a lot more that we don’t know about hereditary factors in pancreatic cancer risk,” Klein said.

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