Yunpeng Yu

M.S.

Indiana University

Biostatistician and Ph.D. student

PLCO (Learn more about this study)

PLCO-1088

Nov 1, 2022

Association between use of non-steroidal anti-inflammatory drugs (NSAIDs) and risk of pancreatic cancer in a national prospective cohort study

Pancreatic cancer is currently the third leading cause of cancer death in the U.S. and has been projected to rank second by 2030. Approximately 80% of patients with pancreatic cancer are diagnosed at advanced stages due to the rapid progression of tumors and the lack of effective screening tests. The five-year relative survival rate for patients with pancreatic cancer stands at only 11.5%. Although cigarette smoking, type 2 diabetes, and chronic pancreatitis have been identified as risk factors for pancreatic cancer, the etiology of pancreatic cancer remains largely elusive. Therefore, it is critical to identify modifiable risk factors for the primary prevention of pancreatic cancer. Periodontitis, pancreatitis, and microbiota dysbiosis in saliva and stool have been associated with an increased risk of pancreatic cancer in epidemiological studies. These findings suggest that inflammation plays a crucial role in pancreatic carcinogenesis. Non-steroidal anti-inflammatory drugs (NSAIDs) (aspirin, etc.) are commonly used medications that alleviate inflammation by inhibiting cyclooxygenase and subsequently reducing the production of prostaglandins (inflammation mediators). Thus, it is possible that the regular use of NSAIDs confers a reduced risk of pancreatic cancer. However, the results of previous studies on this association have been inconsistent. Moreover, few studies have examined the interactions between use of NSAIDs and established risk factors in relation to pancreatic cancer. Therefore, it is interesting and impactful to investigate the association between use of NSAIDs and risk of pancreatic cancer among participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The proposed study seeks to: 1) evaluate the association between use of NSAIDs and risk of pancreatic cancer; and 2) investigate the interactions of NSAID use with BMI, cigarette smoking, and type 2 diabetes on pancreatic cancer risk. Hazard ratios and 95% confidence intervals will be calculated using the Cox proportional hazards regression analysis to estimate the effect of NSAID use on the development of pancreatic cancer. Age, sex, race, BMI, cigarette smoking, diabetes, and family history will be adjusted as potential confounders as they are established or suspected risk factors for pancreatic cancer. We will further examine whether the use of NSAIDs interacts with BMI, cigarette smoking, and diabetes to modulate pancreatic cancer risk. Stratified analysis by effect modifier(s) will be performed if any of those interactions tested is statistically significant. The expected results of the proposed study may lead to an improved understanding of the roles of inflammatory conditions in the etiology of pancreatic cancer and thereby open up new avenues for its chemoprevention.