Association of glycated hemoglobin with risk of pancreatic cancer in high-risk individuals based on genetic and family history.

BACKGROUND: Screening for pancreatic cancer (PC) is suggested for high-risk individuals (HRI). Additional risk factors may enhance early detection in this population.

METHODS: Retrospective cohort study among patients with germline variants and/or familial pancreatic cancer in an integrated healthcare system between 2003-2019. We calculated incidence rate (IR) by risk category and performed a nested case-control study to evaluate relationship between HbA1C and PC within 3 years prior to diagnosis(cases) or match date(controls). Cases were matched 1:4 by age, sex, and timing of HbA1c. Logistic regression was performed to assess independent association with PC.

RESULTS: We identified 5,931 HRIs: 1175(19.8%) familial PC, 45(0.8%) high-risk germline variants (STK11, CDKN2A), 4097(69.1%) had other germline variants (ATM, BRCA 1, BRCA 2, CASR, CDKN2A, CFTR, EPCAM, MLH1, MSH2, MSH6, PALB2, PRSS1, STK11, TP53), and 614(10.4%) had both germline variants and family history. 68 (1.1%) patients developed PC; 50% were metastatic at diagnosis. High-risk variant was associated with greatest risk of PC, IR=85.1(95% CI: 36.7-197.6)/10,000 person-years, other germline variants and FDR had IR=33 (18.4, 59.3) while IR among ≥2 FDR alone was 10.7 (6.1, 18.8). HbA1c was significantly higher among cases vs. controls (median=7.0% vs. 6.4%, p=0.02). In multivariable analysis, every 1% increase in HbA1c was associated with 36% increase in odds of PC (OR=1.36, 95% CI: 1.08-1.72). Pancreatitis was independently associated with risk of PC (OR 3.93, 95% CL1.19,12.91).

CONCLUSION: Risk of PC varies among high-risk individuals. HbA1c and history of pancreatitis may be useful additional markers for early detection in this patient population.