Association Between Genetic Polymorphisms in the Prostate-Specific Antigen Gene Promoter and Serum Prostate-Specific Antigen Levels

Cramer, Scott D.; Chang, Bao Li; Rao, Anuradha; Hawkins, Gregory A.; Zheng, S. Lilly; Wade, Wendy; Cooke, Roger T.; Thomas, Lance R.; Bleecker, Eugene R.; Catàlona, William J.; Sterling, David A.; Meyers, Deborah A.; Ohar, Jill A.; Xu, Jianfeng

doi:10.1093/jnci/95.14.1044

Cited by 72 publications

(75 citation statements)

References 30 publications

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“…No consensual changes were observed within any sample types. Previous experiments have indicated a tendency for SNPs in the KLK locus to exhibit strong linkage disequilibrium (Cramer et al, 2003;. Indeed, these two SNPs were linked to each other.…”

Section: Discussionmentioning

confidence: 91%

“…Even though intragenic mutations have not been identified for the kallikrein genes examined to date, KLK3 (Majumdar and Diamandis, 1999) and KLK10 (Liu et al, 1996), a plethora of single-nucleotide polymorphisms (SNPs) exist within KLK coding and promoter/enhancer regions and may have clinical significance. For example, SNPs in the KLK3 promoter may account for individual variation in serum prostate-specific antigen levels and even cancer susceptibility (Tsuyuki et al, 1997;Xue et al, 2000;Cramer et al, 2003). Similarly, a nonsynonymous SNP in exon 3 of KLK10 is associated with a higher prostate cancer risk (Bharaj et al, 2002).…”

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confidence: 99%

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Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects

et al. 2007

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The human tissue kallikrein family (KLK for protein; KLK for gene) includes 15 members. Twelve kallikreins, including KLK6, are concurrently upregulated in ovarian cancer. However, the mechanism of this phenomenon remains unclear. In this study, we measured KLK6 expression in a large series of ovarian tissue cytosols and examined possible mechanisms of KLK6 up-regulation in ovarian cancer. Using a newly developed enzyme-linked immunosorbent assay (ELISA) with two monoclonal antibodies, we quantified KLK6 expression in ovarian tissue cytosols, and confirmed the upregulation of KLK6 in ovarian cancer and its unfavourable prognostic value. We then examined KLK6 mRNA expression using reverse transcription -polymerase chain reaction and established its good concordance with KLK6 protein expression. This finding suggested that the KLK6 gene is under transcriptional regulation. We then scrutinised a few mechanisms that could explain KLK6 upregulation. The relative abundance of two KLK6 mRNA transcripts was studied; we found the same differential expression pattern in all samples, regardless of KLK6 levels. Genomic mutation screening of all exons and the 5 0 -flanking region of the KLK6 gene identified two linked single-nucleotide polymorphisms in the 5 0 -untranslated region, but neither correlated with KLK6 expression. Ovarian cell lines were separately treated with five steroid hormones. None of the treatments produced significant effects on KLK6 expression. We conclude that KLK6 is transcriptionally upregulated in ovarian cancer, but probably not through alternative mRNA transcript expression, genomic mutation, or steroid hormone induction.

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Section: Discussionmentioning

confidence: 91%

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confidence: 99%

Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects

et al. 2007

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“…6 In 2003, Cramer et al 7 reported that specific germline genetic polymorphisms in the promoter region of the PSA gene were associated with higher serum PSA levels among 409 Caucasian male subjects (mean age 63.7 years). They further suggested that these polymorphisms may be useful in refining the recommendations for use of serum PSA levels for prostate cancer screening.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the prostate-specific antigen gene promoter do not predict serum prostate-specific antigen levels in African-American men

Beebe‐Dimmer

Lange²,

Cain

et al. 2005

Prostate Cancer Prostatic Dis

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A major problem with the use of serum prostate-specific antigen (PSA) in predicting prostate cancer risk is the considerable variability of such measurements. Cramer et al. identified a set of singlenucleotide polymorphisms (SNPs) in the upstream regulatory region of the PSA gene that were each associated with increased promoter activity and serum PSA, further suggesting that genotyping these SNPs could be useful in improving the predictive value of PSA screening. In order to replicate this finding, DNA samples from 475 African-American men were genotyped for the same SNPs and no association was observed with either serum PSA level or prostate cancer diagnosis.

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“…The most commonly used biomarker for prostate cancer is prostate specific antigen (PSA) (2,3), but it has well known limitations in accuracy (4,5). Besides malignancy of variable severity, increased plasma PSA levels can also reflect inflammatory conditions and benign hyperplasia of the prostate, necessitating the search for better biomarkers (2,6).…”

mentioning

confidence: 99%

Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer

Tavoosidana

Ronquist

Darmanis

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

199

173

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Prostasomes are microvesicles (mean diameter, 150 nm) that are produced and secreted by normal and malignant prostate acinar cells. It has been hypothesized that invasive growth of malignant prostate cells may cause these microvesicles, normally released into seminal fluid, to appear in interstitial space and therewith into peripheral circulation. The suitability of prostasomes as blood biomarkers in patients with prostate cancer was tested by using an expanded variant of the proximity ligation assay (PLA). We developed an extremely sensitive and specific assay (4PLA) for detection of complex target structures such as microvesicles in which the target is first captured via an immobilized antibody and subsequently detected by using four other antibodies with attached DNA strands. The requirement for coincident binding by five antibodies to generate an amplifiable reporter results in both increased specificity and sensitivity. The assay successfully detected significantly elevated levels of prostasomes in blood samples from patients with prostate cancer before radical prostatectomy, compared with controls and men with benign biopsy results. The medians for prostasome levels in blood plasma of patients with prostate cancer were 2.5 to sevenfold higher compared with control samples in two independent studies, and the assay also distinguished patients with high and medium prostatectomy Gleason scores (8/9 and 7, respectively) from those with low score (≤6), thus reflecting disease aggressiveness. This approach that enables detection of prostasomes in peripheral blood may be useful for early diagnosis and assessment of prognosis in organ-confined prostate cancer.

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Association Between Genetic Polymorphisms in the Prostate-Specific Antigen Gene Promoter and Serum Prostate-Specific Antigen Levels

Abstract: Genetic variations in the PSA promoter are associated with serum PSA levels in men without prostatic disease. PSA promoter genotype information may help to refine models of PSA cutoff values.

Cited by 72 publications

References 30 publications

Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects

Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects

Polymorphisms in the prostate-specific antigen gene promoter do not predict serum prostate-specific antigen levels in African-American men

Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer

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