Are Prediagnostic Biomarkers of Inflammation and an Empirically Based Proinflammatory Dietary Pattern Associated With Poorer Pancreatic Cancer Survival?

Pancreatic cancer is a leading cause of cancer deaths, ranking third for mortality in the United States. Its incidence has been increasing in the United States (1) and worldwide since the mid1990s, particularly in developed countries (2). Because there are no effective screening methods for detection of this malignancy, it is typically diagnosed at advanced stages, when there is no cure, which contributes to a poor 5-year survival rate of 10% (1). More than 80% of pancreatic cancer patients are diagnosed with metastatic disease or regional spread to the lymph nodes (1). Identifying factors from which therapeutic strategies might be developed could help improve survival. Diet, in particular, is a potentially modifiable factor that is safe and patient empowering. Chronic inflammation is known to play a role in pancreatic cancer etiology and pathogenesis, with the most direct link derived from associations with chronic pancreatitis (3). Obesity, diabetes, and tobacco use are proinflammatory conditions that have been associated with pancreatic cancer risk (4-6) as well as reduced pancreatic cancer survival (7-10). In this issue of the Journal, Yuan et al. (11) carefully evaluated the associations between prediagnostic measures of plasma inflammatory biomarkers, an empirically based proinflammatory dietary pattern (EDIP), and survival after pancreatic cancer diagnosis. The prediagnostic biomarkers included a single measure of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-a receptor 2 (TNF-aR2) measured on 492 pancreatic cancer ductal adenocarcinoma cases that were part of an earlier nested case-control study in the Health Professionals Follow-Up Study, the Nurses’ Health Study, the Physicians’ Health Study I, the Women’s Health Initiative Observational Study, and the Women’s Health Study (12). In addition to evaluating each biomarker separately, the authors created a score ranging from 0 to 3 based on summing the number of biomarkers above the medians of the 3 biomarkers. The EDIP score was derived elsewhere from dietary food predictors of the same inflammatory biomarkers, with a higher score being indicative of higher inflammatory potential (13,14). The food components of the EDIP included 9 antiinflammatory (beer, wine, tea, coffee, dark yellow vegetables, green leafy vegetables, snacks, fruit juice, pizza) and 9 proinflammatory (processed meat, red meat, organ meat, fish, vegetables other than dark yellow vegetables and green leafy vegetables, refined grains, high-energy beverages, low-energy beverages, tomatoes). The EDIP score exposure used in the analysis was calculated as an average based on repeated measures of dietary intake for up to 20 years, and the association with overall survival was conducted by pooling a larger number of pancreatic cancer cases from Health Professionals Follow-Up Study and Nurses’ Health Study (n1⁄4 1153) cohorts compared with the biomarker study. The authors observed that higher prediagnostic inflammatory biomarker score and EDIP score were associated with statistically significantly shorter pancreatic cancer survival (11). A limitation of the study is that the biomarkers and diet were measured years before diagnosis rather than at diagnosis. The authors were not able to directly assess whether the biomarkers or diet at pancreatic cancer diagnosis predicts survival. The blood samples from which the biomarkers were measured were collected on average 6.7 years and up to 24 years before pancreatic cancer diagnosis. In addition, those with the highest inflammatory biomarker score had the shortest time between blood collection and cancer diagnosis. The time frame from initiation of the pancreatic carcinogenic process to cancer death in humans has been estimated to be up to 21 years (15). Pancreatic cancer patients often have gastrointestinal problems, weight loss, or diabetes years before being diagnosed, which can influence biomarkers as well as dietary intake, and it is possible that subclinical disease could be influencing the results. The authors, however, conducted multiple sensitivity analyses to address this, including adjustment for time from blood collection to diagnosis, excluding patients who developed pancreatic cancer within 3 years of diagnosis and stratifying by follow-up time, which did not substantially change the results (11). The differences in median survival time comparing inflammatory biomarker scores of 3 to 0 (3 months) and extreme EDIP score ED IT O R IA L