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Vitamin D status and Pancreatic Cancer Risk

Principal Investigator

Name
Rachael Stolzenberg-Solomon

Degrees
-

Institution
NCI, DCEG, NEB

Position Title
-

Email
stolzenr@dcpcepn.nci.nih.gov

About this CDAS Project

Study
PLCO (Learn more about this study)

Project ID
2006-0293

Initial CDAS Request Approval
Nov 21, 2006

Title
Vitamin D status and Pancreatic Cancer Risk

Summary
There are currently two major efforts to conduct genome wide associations studies (GWAS) to identify genetic markers of susceptibility for endometrial cancer. Dr. Immaculata DeVivo (Harvard University) was recently funded through NCI's ARRA mechanism to support a primary scan in approximately 2,400 endometrial cases and 2,400 matched controls (Illumina 660K) in the USA (ACS, NHS, EPIC, MEC, Connecticut, California Teacher's Cohort, and FHCRC), with replication in US studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2). Drs. Amanda Spurdle (QIMR, Australia) and Doug Easton (Cambridge University, UK) are leading an independent effort to conduct a primary scan (Illumina 610K) of 700 Australian and 700 British endometrial cancer cases, using available scan data for controls. We have previously agreed to replicate findings in the Polish Endometrial Study (PECS) from both efforts and in the PLCO study from the USA scan. A summary of the studies involved in the two GWAS efforts are described in Supplementary Table 1. Here, we propose to conduct a primary scan using the Illumina 660K platform on 600 endometrial cancer cases from PLCO to collaborate with the NCI-funded study to increase the statistical power of the USA-led GWAS. In addition, we are pledged to later participate in pooling with the ongoing Australian/UK-led GWAS. We have approval and funding from DCEG to run these assays. Cases from PLCO will be compared to existing female controls from previous GWAS studies. The combined contribution of 1030 endometrial cases from PECS and PLCO will increase the size of the US primary scan by 30%, resulting in substantial gain in power, particularly for endometrial cancer cases with both risk factor data and tumor samples. Beyond contributing to GWAS efforts, a GWAS scan of the PLCO cases and controls will allow exploring relationships of common variants with circulating hormone levels currently analyzed in PLCO and will create a highly valuable resource for future studies of genetic susceptibility and endometrial cancer outcomes in PLCO. Since the time-window for the ARRA-funded GWAS is limited, PLCO leadership recommended an expedited impact analysis and sample selection process for this proposal under the condition that no samples are released from the repository before final approval.

Aims

We propose to study common genetic variants in relation to endometrial cancer risk in PLCO. This project will create a nested case-control study with extracted DNA from buffy coats/buccal cells in the screened and unscreened arms of PLCO that will also be a resource for future DNA-based studies. In addition, we will provide extensive genotyping data for the PLCO endometrial cancer cases that can be used for future studies of genetic susceptibility in relation to various endpoints. AIM1: Identify and characterize common genetic variants associated with endometrial cancer risk. To conduct genome-wide scan of PLCO endometrial cancer cases and controls that will augment the current GWAS efforts. To contribute data from dense genotyping in PLCO cases and controls to consortial studies that follow up on established susceptibility loci, including fine mapping and associations with tumor characteristics. To carry out gene-environment interactions of established loci, to identify novel loci with weak overall effects using novel statistical methods, and to improve our ability to carry out pathway-based analyses in endometrial cancer in PLCO. AIM2: Explore common genetic variation in relation to endogenous hormone levels. To explore the relation between SNPs and endogenous hormone levels in endometrial cancer cases and controls within PLCO.

Collaborators

Richard Hayes (NCI, DCEG)
Rachael Stolzenberg-Solomon (NCI, DCEG)
Debra Silverman (Occupational Epidemiology Branch)

Related Publications