Pancreatic Cancer Relatives May be at Risk of Syndrome-Related Cancers

For a paper appearing in JAMA Oncology, investigators at the Mayo Clinic, Rochester, Indiana School of Medicine, and elsewhere analyze cancer occurrence in first-degree family members of pancreatic ductal adenocarcinoma (PDAC) patients with pathogenic or likely pathogenic variants in at least one of nine cancer syndrome-related genes analyzed. Based on data for 234 PDAC cases and almost 1,700 parents, siblings, or children, the team saw higher-than-usual rates for six cancer types in these first-degree relatives. Along with a rise in PDAC rates in family members of patients with ATM, BRCA2, or CDKN2A, for example, the authors report a significant uptick in ovarian, breast, and melanoma risk in relatives of PDAC patients with BRCA1, BRCA2, or CDKN2A variants, respectively. Both colon cancers and uterine/endometrial cancers appeared more common in relatives of PDAC patients with Lynch syndrome-related risk variants in mismatch repair genes, on the other hand. "These findings suggest that risk estimation should be assessed for other cancers in families with a history of PDAC for screening, early detection, and intervention incorporating the genetic test results of patients with PDAC," they write. "Future studies including more genes with [pathogenic germline variants (PGV)] yet to be discovered and characterized, other modifiable risk factors such as smoking, and PGV testing of unaffected relatives will help improve the accuracy of cancer risk prediction for first-degree relatives of patients with PDAC."