{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hsu FC"],"funding":["NCI NIH HHS"],"pagination":["1664-1668"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8446906"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(11)"],"pubmed_abstract":["<h4>Importance</h4>Pathogenic germline variants in the ATM gene have been associated with pancreatic cancer risk. Although genetic testing identifies these variants in approximately 1% to 3% of unselected patients with pancreatic cancer, the lifetime risk of pancreatic cancer among individuals with pathogenic ATM variants has not been well estimated.<h4>Objective</h4>To estimate age-specific penetrance of pancreatic cancer in individuals with a pathogenic variant in the ATM gene.<h4>Design, setting, and participants</h4>This was a multicenter cohort study of pancreatic cancer family registries in the US and Canada using pedigree data from 130 pancreatic cancer kindreds with a pathogenic germline ATM variant. Data analyses were performed from January 2020 to February 2021.<h4>Main outcomes and measures</h4>Observational age-specific risk of pancreatic cancer. Penetrance was estimated using modified segregation analysis.<h4>Results</h4>The study population of 130 families (123 [95%] White families) comprised 2227 family members (mean age [SD], 58 [22] years; 1096 [49%] women) with complete records (ie, including familial relationships, pancreatic cancer diagnosis, ATM status, proband status, and age), of which 155 individuals had positive results for an ATM pathogenic variant, 16 had a negative result, and the remainder did not have a test result. In these 130 families, 217 individuals had pancreatic cancer: 78 families had 1 such member; 34 families had 2 such members; and 18 families had 3 or more members with pancreatic cancer. The average (range) age at diagnosis was 64 (31-98) years. The cumulative risk of pancreatic cancer among individuals with a germline pathogenic ATM variant was estimated to be 1.1% (95% CI, 0.8%-1.3%) by age 50 years; 6.3% (95% CI, 3.9%-8.7%) by age 70 years; and 9.5% (95% CI, 5.0%-14.0%) by age 80 years. Overall, the relative risk of pancreatic cancer was 6.5 (95% CI, 4.5-9.5) in ATM variant carriers compared with noncarriers.<h4>Conclusions and relevance</h4>This multicenter cohort study found that individuals with a germline pathogenic ATM variant were at an increased lifetime risk of pancreatic cancer. These risk estimates can help guide decision-making when evaluating the risks and benefits of enhanced early detection surveillance."],"journal":["JAMA oncology"],"pubmed_title":["Risk of Pancreatic Cancer Among Individuals With Pathogenic Variants in the ATM Gene."],"pmcid":["PMC8446906"],"funding_grant_id":["P30 CA006973","P50 CA102701","R01 CA097075","R01 CA132829","R00 CA190889","P50 CA062924"],"pubmed_authors":["Goggins MG","Borgida A","Zogopoulos G","Ukaegbu C","Klein AP","Porter N","Hruban RH","Roberts NJ","Rabe KG","Hsu FC","Gallinger S","Childs E","Petersen GM","Syngal S"],"additional_accession":[]},"is_claimable":false,"name":"Risk of Pancreatic Cancer Among Individuals With Pathogenic Variants in the ATM Gene.","description":"<h4>Importance</h4>Pathogenic germline variants in the ATM gene have been associated with pancreatic cancer risk. Although genetic testing identifies these variants in approximately 1% to 3% of unselected patients with pancreatic cancer, the lifetime risk of pancreatic cancer among individuals with pathogenic ATM variants has not been well estimated.<h4>Objective</h4>To estimate age-specific penetrance of pancreatic cancer in individuals with a pathogenic variant in the ATM gene.<h4>Design, setting, and participants</h4>This was a multicenter cohort study of pancreatic cancer family registries in the US and Canada using pedigree data from 130 pancreatic cancer kindreds with a pathogenic germline ATM variant. Data analyses were performed from January 2020 to February 2021.<h4>Main outcomes and measures</h4>Observational age-specific risk of pancreatic cancer. Penetrance was estimated using modified segregation analysis.<h4>Results</h4>The study population of 130 families (123 [95%] White families) comprised 2227 family members (mean age [SD], 58 [22] years; 1096 [49%] women) with complete records (ie, including familial relationships, pancreatic cancer diagnosis, ATM status, proband status, and age), of which 155 individuals had positive results for an ATM pathogenic variant, 16 had a negative result, and the remainder did not have a test result. In these 130 families, 217 individuals had pancreatic cancer: 78 families had 1 such member; 34 families had 2 such members; and 18 families had 3 or more members with pancreatic cancer. The average (range) age at diagnosis was 64 (31-98) years. The cumulative risk of pancreatic cancer among individuals with a germline pathogenic ATM variant was estimated to be 1.1% (95% CI, 0.8%-1.3%) by age 50 years; 6.3% (95% CI, 3.9%-8.7%) by age 70 years; and 9.5% (95% CI, 5.0%-14.0%) by age 80 years. Overall, the relative risk of pancreatic cancer was 6.5 (95% CI, 4.5-9.5) in ATM variant carriers compared with noncarriers.<h4>Conclusions and relevance</h4>This multicenter cohort study found that individuals with a germline pathogenic ATM variant were at an increased lifetime risk of pancreatic cancer. These risk estimates can help guide decision-making when evaluating the risks and benefits of enhanced early detection surveillance.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Nov","modification":"2026-05-08T02:01:43.248Z","creation":"2025-02-18T23:56:05.677Z"},"accession":"S-EPMC8446906","cross_references":{"pubmed":["34529012"],"doi":["10.1001/jamaoncol.2021.3701"]}}