biostudies-literatureAntwi SOSU2CEntertainment Industry FoundationStand Up To Cancer-Lustgarten Foundation Pancreatic Cancer Interception Translational Cancer Research GrantCentene Charitable FoundationPancreatic Cancer Action NetworkNational Cancer InstituteNCI NIH HHSAmerican Association for Cancer Research372-381https://www.ebi.ac.uk/biostudies/studies/S-EPMC8825751biostudies-literatureUnknown31(2)<h4>Background</h4>ABO blood group is associated with pancreatic cancer risk. Whether ABO blood group alone or when combined with inherited mutation status of index pancreatic cancer cases (probands) can enhance pancreatic cancer risk estimation in first-degree relatives (FDR) is unclear. We examined FDRs' risk for pancreatic cancer based on probands' ABO blood group and probands' cancer susceptibility gene mutation status.<h4>Methods</h4>Data on 23,739 FDRs, identified through 3,268 pancreatic cancer probands, were analyzed. Probands' ABO blood groups were determined serologically or genetically, and 20 cancer susceptibility genes were used to classify probands as "mutation-positive" or "mutation-negative." SIRs and 95% confidence intervals (CI) were calculated, comparing observed pancreatic cancer cases in the FDRs with the number expected in SEER-21 (reference population).<h4>Results</h4>Overall, FDRs had 2-fold risk of pancreatic cancer (SIR = 2.00; 95% CI = 1.79-2.22). Pancreatic cancer risk was higher in FDRs of mutation-positive (SIR = 3.80; 95% CI = 2.81-5.02) than mutation-negative (SIR = 1.79; 95% CI = 1.57-2.04) probands (<i>P</i> < 0.001). The magnitude of risk did not differ by ABO blood group alone (SIR_{blood-group-O} = 1.57; 95% CI = 1.20-2.03, SIR_non-O = 1.83; 95% CI = 1.53-2.17; <i>P</i> = 0.33). Among FDRs of probands with non-O blood group, pancreatic cancer risk was higher in FDRs of mutation-positive (SIR = 3.98; 95% CI = 2.62-5.80) than mutation-negative (SIR = 1.66; 95% CI = 1.35-2.03) probands (<i>P</i> < 0.001), but risk magnitudes were statistically similar when probands had blood group O (SIR_{mutation-positive} = 2.65; 95% CI = 1.09-5.47, SIR_{mutation-negative} = 1.48; 95% CI = 1.06-5.47; <i>P</i> = 0.16).<h4>Conclusions</h4>There is a range of pancreatic cancer risk to FDRs according to probands' germline mutation status and ABO blood group, ranging from 1.48 for FDRs of probands with blood group O and mutation-negative to 3.98 for FDRs of probands with non-O blood group and mutation-positive.<h4>Impact</h4>Combined ABO blood group and germline mutation status of probands can inform pancreatic cancer risk estimation in FDRs.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive OncologyInfluence of Cancer Susceptibility Gene Mutations and ABO Blood Group of Pancreatic Cancer Probands on Concomitant Risk to First-Degree Relatives.PMC8825751U01 CA210138P50 CA102701R01 CA208517R01 CA097075P30 CA015083SU2C-AACR-DT25–17K01 CA237875R01 CA97075McWilliams RRRabe KGFagan SEHu CBamlet WRPetersen GMAntwi SOMeyer MCouch FJOberg ALChandra SfalseInfluence of Cancer Susceptibility Gene Mutations and ABO Blood Group of Pancreatic Cancer Probands on Concomitant Risk to First-Degree Relatives.<h4>Background</h4>ABO blood group is associated with pancreatic cancer risk. Whether ABO blood group alone or when combined with inherited mutation status of index pancreatic cancer cases (probands) can enhance pancreatic cancer risk estimation in first-degree relatives (FDR) is unclear. We examined FDRs' risk for pancreatic cancer based on probands' ABO blood group and probands' cancer susceptibility gene mutation status.<h4>Methods</h4>Data on 23,739 FDRs, identified through 3,268 pancreatic cancer probands, were analyzed. Probands' ABO blood groups were determined serologically or genetically, and 20 cancer susceptibility genes were used to classify probands as "mutation-positive" or "mutation-negative." SIRs and 95% confidence intervals (CI) were calculated, comparing observed pancreatic cancer cases in the FDRs with the number expected in SEER-21 (reference population).<h4>Results</h4>Overall, FDRs had 2-fold risk of pancreatic cancer (SIR = 2.00; 95% CI = 1.79-2.22). Pancreatic cancer risk was higher in FDRs of mutation-positive (SIR = 3.80; 95% CI = 2.81-5.02) than mutation-negative (SIR = 1.79; 95% CI = 1.57-2.04) probands (<i>P</i> < 0.001). The magnitude of risk did not differ by ABO blood group alone (SIR_{blood-group-O} = 1.57; 95% CI = 1.20-2.03, SIR_non-O = 1.83; 95% CI = 1.53-2.17; <i>P</i> = 0.33). Among FDRs of probands with non-O blood group, pancreatic cancer risk was higher in FDRs of mutation-positive (SIR = 3.98; 95% CI = 2.62-5.80) than mutation-negative (SIR = 1.66; 95% CI = 1.35-2.03) probands (<i>P</i> < 0.001), but risk magnitudes were statistically similar when probands had blood group O (SIR_{mutation-positive} = 2.65; 95% CI = 1.09-5.47, SIR_{mutation-negative} = 1.48; 95% CI = 1.06-5.47; <i>P</i> = 0.16).<h4>Conclusions</h4>There is a range of pancreatic cancer risk to FDRs according to probands' germline mutation status and ABO blood group, ranging from 1.48 for FDRs of probands with blood group O and mutation-negative to 3.98 for FDRs of probands with non-O blood group and mutation-positive.<h4>Impact</h4>Combined ABO blood group and germline mutation status of probands can inform pancreatic cancer risk estimation in FDRs.2022-01-01T00:00:00Z2022 Feb2026-05-08T02:01:24.307Z2025-04-04T08:13:37.534ZS-EPMC88257513478239610.1158/1055-9965.EPI-21-074510.1158/1055-9965.epi-21-0745