Martha Sklavos

-

NCI, DCEG, IIB

-

PLCO (Learn more about this study)

2013-0008

Mar 4, 2013

Anti-Mullerian Hormone and Prostate Cancer Risk

Prostate cancer biomarkers are in high demand as prostate cancer screening via prostate specific antigen (PSA) measurement demonstrates no improvement in prostate-cancer mortality and produces many false positives. Despite the large body of basic research linking anti-müllerian hormone (AMH) to cancer in cell lines and mouse models and the availability of a highly sensitive, reproducible AMH ELISA assay, the proposed study would be the first epidemiological study to investigate the association of AMH with prostate cancer risk in humans. AMH is a peptide hormone within the TGF-beta family. In males, AMH is produced by Sertoli cells within the testes and is best known for its instrumental role in the in utero apoptotic regression of müllerian ducts (cervix, fallopian tubes, uterus, upper 2/3 of the vagina) to confer a male phenotype. AMH levels are extremely high in infants and young boys, significantly decrease at puberty, and remain stable throughout adulthood [1]. There is a growing body of evidence that AMH may be causally related to cancer pathogenesis. Several studies have confirmed AMH-induced growth inhibition in prostate cancer cell lines through an NFKB-dependent mechanism [2-4]. Expression of the ligand binding AMH type 2 receptor (AMHR2) has been identified in human prostate cancer cell lines and in normal and cancerous human prostate tissue [4]. We hypothesize that low levels of AMH are associated with increased risk of prostate cancer and with more aggressive disease. To address this hypothesis we propose a nested case-control study of 1000 prostate cancer cases and 1000 controls within the PLCO screening arm. We plan to measure AMH in pre-diagnostic serum or plasma to determine if low levels of AMH are associated with an increased risk of prostate cancer and disease aggressiveness. This is a novel study that will contribute to the understanding of the role of AMH in prostate cancer pathogenesis.

To determine whether there is an association between pre-diagnostic serum AMH levels and prostate cancer risk:

In Localized/Non-aggressive disease (Gleason Score less than or equal to 7 or Stage less than III)

In Metastatic/Aggressive disease (Gleason Score greater than 7 or Stage greater than or equal to III)