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Patients with pancreatic ductal adenocarcinoma (PDAC) commonly develop symptoms and signs in the 1–2 years before diagnosis that can result in changes to medications. We investigate recent medication changes and PDAC diagnosis in Nurses’ Health Study (NHS; females) and Health Professionals Follow-up Study (HPFS; males), including up to 148,973 U.S. participants followed for 2,994,057 person-years and 991 incident PDAC cases. Here we show recent initiation of antidiabetic (NHS) or anticoagulant (NHS, HFS) medications and cessation of antihypertensive medications (NHS, HPFS) are associated with pancreatic cancer diagnosis in the next 2 years. Two-year PDAC risk increases as number of relevant medication changes increases (P-trend <1 × 10−5), with participants who recently start antidiabetic and stop antihypertensive medications having multivariable-adjusted hazard ratio of 4.86 (95%CI, 1.74–13.6). These changes are not associated with diagnosis of other digestive system cancers. Recent medication changes should be considered as candidate features in multi-factor risk models for PDAC, though they are not causally implicated in development of PDAC.

Background: Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the prediagnostic period with patient survival has not been investigated. Methods: Adipokine levels were measured in prospectively collected samples from 472 pancreatic cancer patients. Due to sex-specific differences in adipokine levels, associations were evaluated separately for men and women. In a subset of 415 patients, we genotyped 23 nucleotide polymorphisms (SNPs) in adiponectin receptor genes (ADIPOR1, ADIPOR2) and 30 SNPs in the leptin receptor gene (LEPR). Results: Adiponectin levels were inversely associated with survival in women (HR=1.47, 95% CI: 1.03-2.11, comparing top to bottom quartile) but not in men (HR=0.93, 95% CI: 0.54-1.59). The SNPs rs10753929 and rs1418445 in ADIPOR1 were associated with survival in the combined population (per minor allele HR=0.66, 95% CI: 0.51-0.84, and HR=1.33, 95% CI: 1.12-1.58, respectively). Among SNPs in LEPR, rs12025906, rs3790431, and rs17127601 were associated with survival in the combined population [HRs (95% CI) of 1.54 (1.25-1.90), 0.72 (0.59-0.88), and 0.70 (0.56-0.89), respectively], while rs11585329 was associated with survival in men only (HR=0.39, 95% CI: 0.23-0.66) (P-interaction=0.0002). Conclusions: High levels of adiponectin in the prediagnostic period were associated with shorter survival among women, but not among men with pancreatic cancer. Several polymorphisms in ADIPOR1 and LEPR are associated with patient survival. Impact: Our findings reveal the association between adipokine signaling and pancreatic cancer survival and demonstrate the importance of examining obesity-associated pathways in relation to pancreatic cancer in a sex-specific manner.

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