It remains unclear how pre-existing depression, anxiety, and diabetes of different durations are associated with the risk of pancreatic cancer, its clinical characteristics, treatment modalities, and subsequent survival.
From a register-based random sample of Finns residing in Finland at the end of the period 1987–2007, 6492 patients diagnosed with primary pancreatic cancer in 2000–2014, and 32 460 controls matched for birth cohort and sex, were identified. Pre-existing depression, anxiety, and diabetes were ascertained from the records of prescribed medication purchases. Information on pancreatic cancer outcomes was obtained from the Finnish cancer register. Data were analyzed using logistic and Cox regressions.
The risk of developing pancreatic cancer was found to be associated with long-term anxiety (treatment started 36 + months before the cancer diagnosis) (odds ratio (OR): 1.13, 95% confidence interval (95%CI): 1.04–1.22) and long-term diabetes (OR 1.72, 95%CI 1.55–1.90), as well as with new-onset (treatment started 0–24 months before the cancer diagnosis) depression (OR 1.59, 95%CI 1.34–1.88), anxiety (OR 1.76, 95%CI 1.50–2.07), and diabetes (OR 3.92, 95%CI 3.44–4.48). However, the effects of these new-onset conditions were driven by cases that began treatment within 3 months before the cancer diagnosis (concomitant period). Patients with long-term depression, anxiety and diabetes and those with new-onset anxiety had a higher risk of not receiving standard treatments. Lower survival was found for pancreatic cancer patients with new-onset depression (hazards ratio (HR) 1.38, 95%CI 1.16–1.64). Survival was not associated with pre-existing anxiety or diabetes.
The associations between pancreatic cancer risk and pre-existing depression and anxiety were mostly driven by concomitant effects. Individuals with diabetes, regardless of duration, should be closely monitored for pancreatic cancer. Pancreatic cancer patients with new-onset depression should be targeted to improve their survival.
- • How pre-existing depression, anxiety, and diabetes of different durations are associated with pancreatic cancer remain unclear.
- • Elevated pancreatic cancer risk was associated with new-onset anxiety, as well as with long-term, recent- and new-onset diabetes.
- • Large concomitant effects of pre-existing depression, anxiety, and diabetes on pancreatic cancer risk were observed.
- • Worse survival was only found in pancreatic cancer patients with new-onset depression.
Pancreatic cancer is one of the most fatal cancers with the worst prognosis, largely because it is an aggressive form of cancer that has few symptoms until it becomes advanced . Potential risk factors for pancreatic cancer include tobacco smoking, alcohol consumption, occupational exposures, obesity, diabetes, chronic infections, and certain genetic factors . However, many possible risk factors – such as pre-existing depression and anxiety – are still poorly understood . It has long been known that pancreatic cancer patients have high rates of depression and other psychological disorders . A review reported a prevalence of depression ranging from 33% to 50% in patients with pancreatic cancer, which was higher than the levels found in patients with other forms of cancer such as lung, breast, and oropharyngeal cancers . This observation was confirmed in another review, which also noted the frequent coexistence of depression and anxiety in pancreatic cancer patients . Depression has also been shown to be a precursor of pancreatic cancer . A large-scale study based on health claims of inpatients and outpatients in the US found that the risk of pancreatic cancer doubled in men with mental disorders, and that these disorders were, on average, diagnosed 1.5 years before the pancreatic cancer diagnosis; however, this was not observed in women .
Nonetheless, researchers have called into question the direction of the relationship: whether depression and anxiety are precursors to pancreatic cancer, or whether these conditions are psychological consequences of being diagnosed with pancreatic cancer . Patients’ psychological distress may start to increase when they are undergoing medical examinations and are suspected of suffering from pancreatic cancer. Thus, studies that examine the associations between the timing of the onset of depression and anxiety and pancreatic cancer risk are both necessary and important. In addition, there is evidence that the association between having diabetes and pancreatic cancer risk varies depending on when the patient was diagnosed with diabetes . The risk of pancreatic cancer associated with recent-onset diabetes (e.g., 2–3 years prior to the diagnosis of pancreatic cancer) has been found to be greater than that associated with long-term diabetes . A meta-analysis showed that pancreatic cancer risk decreased as the duration of diabetes increased . A similar gradient may also exist between the timing of the onset of depression and anxiety and pancreatic cancer risk.
The risk factors for pancreatic cancer may also affect the clinical characteristics of pancreatic cancer and its treatments and outcomes. Cancer patients with pre-existing depression, including pancreatic cancer patients, have been found to have worse survival than those without depression . The relationships between pre-existing mental disorders and the cancer stage and treatments remain unclear . Similarly, although an association between diabetes and pancreatic cancer survival has been previously reported , no consensus has been reached on whether the timing of the onset of diabetes influences survival . Therefore, there have been calls for further research on the relationship between diabetes and the prognosis of pancreatic cancer .
The present study, using longitudinal Finnish registry data from 1995 to 2015, investigated (1) how pre-existing depression, anxiety, and diabetes with different durations affect the risk of pancreatic cancer, and (2) how having these pre-existing conditions influences the stage of pancreatic cancer, the treatment modalities, and the survival of pancreatic cancer patients.