Skip to Main Content

An official website of the United States government

View Results from this Project

Serum Estrogens and Subsequent Risk of Prostate Cancer

Principal Investigator
Name
Amanda Black
Degrees
-
Institution
NCI, DCEG, EBP
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2009-0562
Initial CDAS Request Approval
Jan 28, 2010
Title
Serum Estrogens and Subsequent Risk of Prostate Cancer
Summary
Emerging data from laboratory studies suggest that estrogens may influence prostate carcinogenesis. However, epidemiologic data on estrogens and prostate cancer in humans very limited, largely due to the lack of sensitive and specific assays of measuring estrogens and estrogen metabolites (EM) with precision. We seek to determine whether pre-diagnostic serum levels of estradiol and 14 EMs are associated with subsequent prostate cancer risk in a large nested case-control study of prostate cancer in the PLCO. A total of 1,422 incident cases and 2,071 controls will be included in the study using a 2-stage design: Stage 1 includes all non-Hispanic Caucasian subjects selected for the androgen study (727 cases and 889 controls) and, if results from Stage 1 are suggestive, Stage 2 study, which includes all non-Hispanic Caucasian subjects selected for CGEMS Phase I that were not included in the proposed Stage 1 (430 cases and 430 non-Hispanic Caucasian controls) and African American subjects (265 cases and 729 controls) will be launched for replication and race-specific analysis. We will employ a validated mass spectrometry-based assay that is able to simultaneously detect 15 EMs with high specificity and sensitivity using only 0.4 ml of serum. We will assess whether these 15 EMs are associated with total or aggressive prostate cancer. Since animal models suggest that estrogen-androgen balance may be important in prostate cancer etiology, we will investigate whether androgens modify the effects of EMs on prostate cancer, using existing androgen data. Furthermore, we plan to conduct subgroup analyses in African American men to determine if the effects of EMs on prostate cancer differ by race, which may provide some insight into the racial disparity of this disease. This study will complement existing PLCO data and help clarify the role of estrogen in prostate cancer etiology.
Aims

Our primary hypothesis is that serum estrogens, including estradiol and estrone as well as other EMs, influence the risk of both total and aggressive prostate cancer. To test this hypothesis, we propose the following aims: Primary Aim: To determine the associations between 15 serum EMs (at baseline T0) and 1) total prostate cancer and 2) aggressive prostate cancer. We will use a validated, high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay to measure baseline serum EMs levels in 1,422 incident cases of prostate cancer and 2,071 controls (including 265 African American cases and 729 African American controls) using a 2-stage approach in a nested case-control study within the PLCO Cancer Screening Trial. Stage 1 will include 727 cases and 889 controls, while Stage 2, if needed, will include 430 non-Hispanic Caucasian cases and 430 controls and 265 African American cases and 729 controls. Data from Stage 1 will also inform us the importance of individual EMs that needed to be measured in the Stage 2 study. To assess the effects of EMs, individual serum EMs will be included in logistic models of 1) total prostate cancer and 2) aggressive prostate cancer (Gleason score >7 or stage =3) along with potential confounders, such as age, body mass index, dietary factors, physical activity, smoking, alcohol use, family history of prostate cancer, screening practices, and serum markers of androgen and sex hormone-binding globulin (SHBG). African American cases and controls will be analyzed separately unless the effects are comparable between African Americans and Caucasian groups, in which case, we will combine these two groups in the final analysis to gain statistical power. Secondary Aim: To evaluate the role of estrogen-androgen balance in risk of 1) total prostate cancer and 2) aggressive prostate cancer. Serum androgen and SHBG levels were measured in 727 cases and 889 controls in an earlier PLCO EEMS study (1). Subjects with androgen measurements are part of the Stage 1 design in the proposed study. We will seek approval from PLCO to access these data for the evaluation of estrogen-androgen balance on prostate cancer risk. We will also evaluate potential interactions between EMs and androgens on prostate cancer risk as part of this aim.

Collaborators

Amanda Black (NCI, DCP)
Louise Brinton (NCI, DCEG)
Lisa Chu (NCI, DCEG)
Robert Grubb (Washington University)
Robert Hoover (NCI, DCEG)
Ann Hsing (NCI, DCEG)
Wen-Yi Huang (NCI, DCEG)
Tamra Meyer (NCI, DCEG)
Paul Pinsky (NCI, DCP)
Tim Veenstra (NCI - Frederick)
Xia Xu (NCI - Frederick)
Kai Yu (NCI, DCEG)

Related Publications