MSMB variation and prostate cancer risk

Clues towards a possible fungal etiology

Siobhan Sutcliffe, Angelo Michael Demarzo, Karen Sfanos, Martin Laurence

Research output: Contribution to journalArticle

Abstract

BACKGROUND. With recent advances in high-throughput sequencing technologies, many prostate cancer risk loci have been identified, including rs10993994, a single nucleotide polymorphism (SNP) located near the MSMB gene. Variant allele (T) carriers of this SNP produce less prostate secretory protein 94 (PSP94), the protein product of MSMB, and have an increased risk of prostate cancer (approximately 25% per T allele), suggesting that PSP94 plays a protective role in prostate carcinogenesis, although the mechanisms for such protection are unclear. METHODS. We reviewed the literature on possible mechanisms for PSP94 protection for prostate cancer. RESULTS. One possible mechanism is tumor suppression, as PSP94 has been observed to inhibit cell or tumor growth in in vitro and in vivo models. Another novel mechanism, which we propose in this review article, is that PSP94 may protect against prostate cancer by preventing or limiting an intracellular fungal infection in the prostate. This mechanism is based on the recent discovery of PSP94's fungicidal activity in low-calcium environments (such as the cytosol of epithelial cells), and accumulating evidence suggesting a role for inflammation in prostate carcinogenesis. We provide further details of our proposed mechanism in this review article. CONCLUSIONS. To explore this mechanism, future studies should consider screening prostate specimens for fungi using the rapidly expanding number of molecular techniques capable of identifying infectious agents from the entire tree of life.

Original languageEnglish (US)
Pages (from-to)569-578
Number of pages10
JournalProstate
Volume74
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Prostate
Prostatic Neoplasms
Proteins
Single Nucleotide Polymorphism
Carcinogenesis
Alleles
Mycoses
Cytosol
Neoplasms
Fungi
Epithelial Cells
Inflammation
Calcium
Technology
Growth
Genes

Keywords

  • fungi
  • MSMB
  • prostate cancer
  • prostate secretory protein 94

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

MSMB variation and prostate cancer risk : Clues towards a possible fungal etiology. / Sutcliffe, Siobhan; Demarzo, Angelo Michael; Sfanos, Karen; Laurence, Martin.

In: Prostate, Vol. 74, No. 6, 2014, p. 569-578.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND. With recent advances in high-throughput sequencing technologies, many prostate cancer risk loci have been identified, including rs10993994, a single nucleotide polymorphism (SNP) located near the MSMB gene. Variant allele (T) carriers of this SNP produce less prostate secretory protein 94 (PSP94), the protein product of MSMB, and have an increased risk of prostate cancer (approximately 25{\%} per T allele), suggesting that PSP94 plays a protective role in prostate carcinogenesis, although the mechanisms for such protection are unclear. METHODS. We reviewed the literature on possible mechanisms for PSP94 protection for prostate cancer. RESULTS. One possible mechanism is tumor suppression, as PSP94 has been observed to inhibit cell or tumor growth in in vitro and in vivo models. Another novel mechanism, which we propose in this review article, is that PSP94 may protect against prostate cancer by preventing or limiting an intracellular fungal infection in the prostate. This mechanism is based on the recent discovery of PSP94's fungicidal activity in low-calcium environments (such as the cytosol of epithelial cells), and accumulating evidence suggesting a role for inflammation in prostate carcinogenesis. We provide further details of our proposed mechanism in this review article. CONCLUSIONS. To explore this mechanism, future studies should consider screening prostate specimens for fungi using the rapidly expanding number of molecular techniques capable of identifying infectious agents from the entire tree of life.",
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T1 - MSMB variation and prostate cancer risk

T2 - Clues towards a possible fungal etiology

AU - Sutcliffe, Siobhan

AU - Demarzo, Angelo Michael

AU - Sfanos, Karen

AU - Laurence, Martin

PY - 2014

Y1 - 2014

N2 - BACKGROUND. With recent advances in high-throughput sequencing technologies, many prostate cancer risk loci have been identified, including rs10993994, a single nucleotide polymorphism (SNP) located near the MSMB gene. Variant allele (T) carriers of this SNP produce less prostate secretory protein 94 (PSP94), the protein product of MSMB, and have an increased risk of prostate cancer (approximately 25% per T allele), suggesting that PSP94 plays a protective role in prostate carcinogenesis, although the mechanisms for such protection are unclear. METHODS. We reviewed the literature on possible mechanisms for PSP94 protection for prostate cancer. RESULTS. One possible mechanism is tumor suppression, as PSP94 has been observed to inhibit cell or tumor growth in in vitro and in vivo models. Another novel mechanism, which we propose in this review article, is that PSP94 may protect against prostate cancer by preventing or limiting an intracellular fungal infection in the prostate. This mechanism is based on the recent discovery of PSP94's fungicidal activity in low-calcium environments (such as the cytosol of epithelial cells), and accumulating evidence suggesting a role for inflammation in prostate carcinogenesis. We provide further details of our proposed mechanism in this review article. CONCLUSIONS. To explore this mechanism, future studies should consider screening prostate specimens for fungi using the rapidly expanding number of molecular techniques capable of identifying infectious agents from the entire tree of life.

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