Demetrius Albanes

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NCI

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PLCO (Learn more about this study)

2014-0030

Mar 7, 2014

Pre-diagnostic serum metabolomic profiling and risk of prostate cancer

Although prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer death in most developed populations, there are no well-established modifiable risk factors for the disease. Further, several organizations have recommended against routine prostate-specific antigen (PSA) screening, the one available early detection marker, because of over-diagnosis and over-treatment. A few studies have compared the metabolomic profiles of blood from men with and without prostate cancer and by disease aggressiveness. However, to our knowledge, only one prior study, conducted by our group, examined pre-diagnostic serum metabolomic profiles years in advance of disease in relation to subsequent risk of prostate cancer. This prospective nested case-control study, conducted in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort, a population of Finnish male smokers, found a novel metabolite strongly associated with prostate cancer up to two decades prior to diagnosis (manuscript attached). The present proposal involves a similar nested case-control investigation in the PLCO cohort aimed at replicating the prior associations and examining whether novel metabolites may be detected in this study population.

Primary Aims
1. Examine whether the novel metabolites associated with risk of prostate cancer in the ATBC Study cohort (i.e. 1-steroylglycerol, glycerol, and alpha-ketoglutarate) replicate in the PLCO cohort.

2. Examine whether additional novel metabolites or metabolic pathways from pre-diagnostic serum metabolomic profiles are associated with risk of prostate cancer in the PLCO cohort.

Secondary Aims
1. Examine whether the relation between the novel metabolites associated with risk of prostate cancer in the ATBC Study cohort (i.e. 1-steroylglycerol, glycerol, and alpha-ketoglutarate) differs by smoking status or by prostate cancer aggressiveness at diagnosis.

2. Examine whether the association between additional novel metabolites or metabolic pathways from the pre-diagnostic serum metabolome and risk of prostate cancer differs by smoking status or by prostate cancer aggressiveness at diagnosis.