Johns Hopkins research team explores link between pancreatic cancer and multiple genetic variation

Johns Hopkins research team explores link between pancreatic cancer and multiple genetic variationA research team at Johns Hopkins has found a link between multiple genetic changes and increased risk of pancreatic cancer. The detailed results of the study have been published in Nature Genetics. In a genome-wide association study believed to be the largest of its kind, Johns Hopkins researchers have uncovered four regions in the human genome where changes may increase the risk of pancreatic cancer.

The researchers say newly identified genetic variants are located at several positions on human chromosomes, including position 17q25.1, which may increase cancer risk by 38 percent for each copy that is present in the genome; position 7p13, which may increase the risk by 12 percent; and position 3q29, which may increase the risk by 16 percent. Position 2p13.3, another genetic region pinpointed in the study, was previously linked with pancreatic cancer risk in a study of Han Chinese people, and the current study provides more definitive evidence of different genetic changes in that region believed to increase pancreatic cancer risk by 14 percent.

"These variants are common in the population, and most individuals who have these variants will never develop pancreatic cancer in their lifetime," cautions Alison Klein, Ph.D., associate professor of oncology at the Johns Hopkins University School of Medicine. "However, identifying and understanding these changes can lead to a better understanding of why some people develop pancreatic cancer. If we combine this information with data on other pancreatic cancer risk factors, we may be able to identify and one day screen high-risk groups."

Further studies of the function of these genetic regions are already underway, Klein says, but several appear related to DNA repair, cell growth and tumor suppression.

Results of the genomic analysis, published online June 22 in Nature Genetics by Klein and her colleagues, included genetic information from 9,925 patients with pancreatic cancer and 11,569 healthy individuals. Some of the samples were newly genotyped, and others were analyzed in a so-called meta-analysis of already published data. The newly-genotyped blood samples were obtained from eight medical centers in North America, central Europe and Australia, and took four years to collect and analyze.

Klein, a member of the Johns Hopkins Kimmel Cancer Center and Sol Goldman Pancreatic Cancer Research Center, says the study also confirms the connection between pancreatic cancer risk and several genetic variants linked to other cancers. For instance, the scientists noted a connection between pancreatic cancer risk and variation in the TP63 gene, and other studies have suggested the TP63 variations also are related to lung and bladder cancers, among others.

"We knew there were more genetic variants to be found, and the large number of pancreatic cancers in the current analysis gave our study more power to find more novel genes," she says.

Pancreatic cancer is the fourth leading cause of cancer death in the United States, but it is not as commonly diagnosed as other cancers, such as breast or colorectal cancers. Patients with pancreatic cancer are also often diagnosed at late stages of the disease, making it tougher to identify genetic risk factors, says Klein.