Introduction
Diabetes mellitus (DM) is a substantial risk factor for pancreatic cancer (PC). Concurrently, aspirin has been implicated to have chemopreventive effect against cancer of digestive system. However, studies regarding the effect of aspirin on mitigating PC risk among DM populations remain scant.
Aims & Methods
We aimed to examine whether regular use of aspirin was associated with a reduced risk of PC after adjusting for known risk factors among type 2 diabetes (T2D) patients.
This was a territory-wide, retrospective cohort study of newly diagnosed T2D patients between 2001 and 2015 in Hong Kong. Exclusion criteria included <18 years old, history of PC, pancreatic neuroendocrine tumor, serous cystadenoma, chronic or acute pancreatitis, and pancreatic cyst. The outcome of interest was pancreatic cancer. Adjusted hazard ratios (aHRs) for outcomes associated with aspirin use were calculated using multivariable Cox regression models. Aspirin use was treated as a time-varying covariates (≥180 days use at each yearly interval) in the analysis to address and minimize immortal-time bias.
Results
We identified 342,920 T2D patients (52.2% male, mean age: 58.8±11.6 years), including 43,634 (12.7%) aspirin users. During a mean follow-up of 11.1±4.2 years, 1,114 (0.3%) patients developed PC, with an incidence rate of 2.92 per 10,000 person-years. Aspirin use was associated with a reduced PC risk (HR 0.55, 95%CI 0.46-0.66). When compared with the reference group (never use), a lower risk was observed with increasing frequency, with the exception of daily use. In addition, longer durations of aspirin use were associated with a progressively lower PC risks (HR 0.83, 95%CI 0.71-0.96, for less than five years of use; HR 0.56, 95%CI 0.45-0.69, for five to ten years of use; and HR 0.27, 95%CI 0.20-0.36, for ten or more years of use. Both frequency and duration of aspirin use demonstrated statistically significant trends (Ptrend <0.001) (Table 1).
Table 1. HRs and 95% CIs for the association between frequency and duration of aspirin use and risk of pancreatic cancer
| Aspirin use | No. of patients (n=342,920) | No. of PC (n=1,114) | HR (95% CI) | P* | Ptrend* |
Frequency
Never user |
219,674 |
736 | ref | - |
<0.001 |
| <Monthly use | 13,809 | 52 | 0.66 (0.50-0.88) | 0.004 |
|
Monthly to <weekly use
| 13.274 | 44 | 0.59 (0.43-0.80) | <0.001 |
|
Weekly to <daily use
| 73,232 | 201 | 0.54 (0.46-0.63) | <0.001 |
|
Daily use
| 22,931 | 81 | 0.90 (0.69-1.16) | 0.401 |
|
Duration (years)
Never user
|
219,674 |
736 | ref | - |
<0.001 |
| <5 | 54,029 | 223 | 0.83 (0.71-0.96) | 0.015 |
|
| 5 - <10 | 40,003 | 99 | 0.56 (0.45-0.69) | <0.001 |
|
≥10
| 29,214 | 56 | 0.27 (0.20-0.36) | <0.001 |
|
*Cox proportional hazards model was used to calculate the
P values. Adjusted covariates included age, sex, lifestyle factors (body mass index, smoking, and alcohol use), metabolic disorders (dyslipidemia and hypertension), time-weighted mean HbA1c, DM complications, cardiovascular diseases, other anti-diabetic medications, non-aspirin non-steroidal anti-inflammatory drugs, and statins.
Abbreviation: CI, confidence interval; HR, hazard ratios; PC, pancreatic cancer; ref, reference
Conclusion
Aspirin use was associated with a reduction in PC risk among T2D patients, which was dependent on both frequency and duration of use. Notably, this trend was observed with increased frequency of use, with the exception of daily use. Further studies are warranted to assess long-term effects and potential risks.
