Study
PLCO
(Learn more about this study)
Project ID
2008-0256
Initial CDAS Request Approval
Jul 17, 2009
Title
Serum Melatonin and Subsequent Risk of Prostate Cancer
Summary
Epidemiologic data from occupational cohorts on shift workers and airline pilots suggest that circadian rhythm disruptions increase the risk of prostate cancer (1-5). In humans, the overall circadian rhythm is mediated by the hormone melatonin in response to the environment, primarily light. Preliminary data suggest that several genes that influence the biosynthesis and action of melatonin may affect prostate cancer risk. For example, in an earlier pilot study, we reported that a variant in one of the 9 core circadian genes, CRY2, was significantly associated with increased prostate cancer risk (6). In addition, melatonin is a broad spectrum antioxidant (see (7) for review) and has a direct influence on androgens (8, 9) and androgenic action (10, 11). Furthermore, clinical data, although limited, suggest that serum melatonin levels in prostate cancer patients have an inverse correlation with stage and tumor size (12-14), while data from animal studies show that melatonin suppresses prostate tumor growth (15, 16). To date, however, there are no epidemiologic data on the role of melatonin, partly due to the relatively low concentration of melatonin in serum, making it difficult to measure in large-scale epidemiologic studies. To investigate the role of melatonin in prostate cancer, we propose to conduct the first prospective epidemiologic study to test the hypothesis that low serum melatonin levels increase prostate cancer risk. In the past year, together with USC, we have optimized a serum melatonin assay suitable for epidemiologic studies. In collaboration with PLCO, CGEMS, and USC, we plan to conduct a nested case-control study of prostate cancer (about 800 cases and 800 controls), and measure serum melatonin in premorbid serum samples collected at the baseline of the PLCO trial. Because these subjects are also included in the CGEMS genome-wide association studies (GWAS) effort, genotyping data will be available for exploratory analysis.
Aims
We hypothesize that low serum melatonin levels are associated with higher risk for prostate cancer. To test this hypothesis, we propose the following aims: Primary aim: Determine the association between serum melatonin and prostate cancer risk. We will measure serum melatonin level in 770 cases (275 non-aggressive and 495 aggressive) and 800 controls from the standard and expanded nested cases-control study of prostate cancer within the PLCO that is also part of BPC3. With this data, we will use logistic regression analysis to determine the main effects of serum melatonin levels on total prostate cancer risk as well as by disease aggressiveness. Secondary aim: Explore how genes related to melatonin may modify the effect of melatonin on prostate cancer risk (as an expansion to our ongoing CGEMS Value-added Study on circadian genes). Many of the subjects included in the proposed study are also part of CGEMS Phase I and thus we will have existing genotyping data on melatonin-related genes. Similar to the primary aim, we will assess the joint effects by logistic regression analysis on total prostate cancer as well as by disease aggressiveness
Collaborators
Anand Chokkalingam (University of California at Berkeley)
Stephen Chanock (NCI, DCEG)
Frank Stanczyk (University of Southern California)
Richard Hayes (NCI, DCEG)
Ann Hsing (NCI, DCEG)
Wen-Yi Huang (NCI, DCEG)
Qizhai Li (NCI, DCEG)
Sabah Quraishi (NCI, DCEG)
Kai Yu (NCI, DCEG)
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