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Pancreas Cancer Early Detection

Principal Investigator
Name
Paul Lampe
Degrees
-
Institution
Fred Hutchinson Cancer Research Center
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2012-0229
Initial CDAS Request Approval
Oct 22, 2012
Title
Pancreas Cancer Early Detection
Summary
It is axiomatic in clinical oncology that early detection of cancers increases the likelihood of cure. This is especially true of pancreas cancer (i.e., pancreatic ductal adenocarcinoma or PDA), a disease whose onset and progression are effectively obscured by anatomic location, vague and non-localizing symptoms and a complete dearth of noninvasive detection and diagnostic modalities. We have performed high density antibody array analysis of 185 prediagnostic plasma samples from the Womens Health Initiative (WHI) Observational Study from women who would develop pancreatic ductal adenocarcinoma 0.1 - 7 years after blood draw to discover potential early detection biomarkers. We found 42 biomarkers significantly increased (greater than 2 fold, p less than 0.05) in people that die from PDA 0.1 - 4 years after blood draw (103 cases). Eight of these biomarkers are of particular interest because they were observed with multiple independent antibodies, they showed the largest/most consistent changes, and/or they also were found in an analysis of 37 plasma samples taken from men and women just prior to PDA diagnosis. We propose to test these 42 biomarker candidates markers in Aim 1 using PLCO samples. Disease etiology, subject sex, family history, etc., could affect biomarker expression in plasma. For Aim 2 we will, therefore, evaluate the potential influence of clinical and epidemiologic factors, including age, gender, body mass index, family history of pancreas cancer, diabetes history, alcohol use, and smoking history on biomarker performance and risk prediction. Positive confirmation of early detection biomarkers in two large prediagnostic sample sets would lead to formal, blinded validation studies most likely in conjunction with the Early Detection Research Network.
Aims

We propose a nested case-control early detection biomarker validation study within the PLCO of people that are diagnosed with PDA subsequent to at least 1 study blood draw. Our hypothesis is that given the vascular nature and secretory function of the normal pancreas, plasma biomarkers exist that can predict disease earlier than overt symptoms. Identification of these markers may also help us understand the biology behind the increased risk of pancreas cancer associated with diabetes and why women have a 10:1 ratio of the mucinous cystic neoplasm (MCN) vs. Pancreatic Intraepithelial Neoplasia (PanIN) pathway to PDA and lower rates overall. Given the disease incidence (i.e., similar to ovarian cancer), whether one can find early detection biomarkers that could be used in a general population setting is debatable, but, in any case, understanding male-female differences in pancreas cancer etiology and the role insulin resistance and diabetes and other risk factors such as family history play in PDA could lead to viable tests for targeted high risk populations. Certainly our studies using prediagnostic pancreas cancer samples from the WHI and diagnostic PDA samples from the Pancreas Cancer Clinic at the FHCRC clearly indicate that many consistent proteomic changes are detectable using our high dimensional array. We posit that for an effective early detection screening test, one should use prediagnostic samples preferably in a high dimensional assay to maximize the chance of discovering biomarkers. Combined with our data collected from WHI samples from women that get pancreas cancer, plasma from the PLCO will yield the richest set of potential biomarkers for subsequent blinded validation. Our specific aims are:

Aim 1: To use PLCO samples to evaluate 42 potential biomarker candidates (i.e., those with greater than 2x increase and p less than 0.05) markers obtained from analysis of 103 women enrolled in the WHI study who die from PDA within 4 years.

Aim 2: To evaluate how a variety of clinical and epidemiologic factors, including age, gender, body mass index, family history of pancreas cancer, diabetes history, alcohol use, and smoking history, potentially impact biomarker performance and risk prediction.

Collaborators

Christopher I. Li (Fred Hutchinson Cancer Research Center)
Paul Lampe (Fred Hutchinson Cancer Research Center)

Approved Addenda This project has one or more approved addenda.
  • Use residual plasma to measure microRNAs