Influence of Cancer Susceptibility Gene Mutations and ABO Blood Group of Pancreatic Cancer Probands on Concomitant Risk to First-Degree Relatives

Samuel O. Antwi, Kari G. Rabe, William R. Bamlet, Margaret Meyer, Shruti Chandra, Sarah E. Fagan, Chunling Hu, Fergus J. Couch, Robert R. McWilliams, Ann L. Oberg, Gloria M. Petersen

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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 firstdegree relatives (FDR) is unclear. We examined FDRs' risk for pancreatic cancer based on probands' ABO blood group and probands' cancer susceptibility gene mutation status. Methods: 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 "mutationpositive"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). Results: 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 ofmutation-positive (SIR= 3.80; 95% CI= 2.81-5.02) than mutation-negative (SIR = 1.79; 95% CI = 1.57-2.04) probands (P < 0.001). The magnitude of risk did not differ by ABO blood group alone (SIRblood-group-O=1.57; 95%CI=1.20-2.03, SIRnon-O= 1.83; 95% CI= 1.53-2.17; P = 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 mutationnegative (SIR = 1.66; 95% CI = 1.35-2.03) probands (P < 0.001), but risk magnitudes were statistically similar when probands had blood group O (SIRmutation-positive = 2.65; 95% CI = 1.09-5.47, SIRmutation-negative = 1.48; 95% CI = 1.06-5.47; P = 0.16). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)372-381
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume31
Issue number2
DOIs
StatePublished - Feb 2022

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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