A Systematic Review of Replication Studies of Prostate Cancer Susceptibility Genetic Variants in High-Risk Men Originally Identified from Genome-Wide Association Studies

Ishak, Miriam B.; Giri, Veda N.

doi:10.1158/1055-9965.epi-11-0312

Cited by 43 publications

(26 citation statements)

References 51 publications

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“…For example, recent studies using the Collaborative Oncological Gene-environment Study iCOGS array have provided more in-depth coverage that permitted the identification of 23 novel genetic variants, called single nucleotide polymorphisms (SNPs), that are associated with increased PCa risk. These contribute to a seemingly growing panel of approximately 100 panels of unique SNPs that have been associated with PCa susceptibility [1–11]. Although their association with PCa risk is well established, their association with adverse pathologic features (eg, high-grade disease) and clinical outcomes remains underinvestigated.…”

Section: Introductionmentioning

confidence: 99%

Associations Between iCOGS Single Nucleotide Polymorphisms and Upgrading in Both Surgical and Active Surveillance Cohorts of Men with Prostate Cancer

et al. 2016

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Background Associations have been documented recently between some of the 23 single nucleotide polymorphisms newly discovered with the Collaborative Oncological Gene-environment Study iCOGS array that indicate prostate cancer (PCa) risk and aspects of disease aggressiveness. The utility of these iCOGS SNPs remains to be determined in active surveillance (AS). Objective To determine associations between iCOGS SNPs and upgrading among men who underwent surgical treatment and AS for low-risk PCa. Design, setting, and participants The genotypes of the 23 iCOGS SNPs were determined for all white subjects with biopsy Gleason score (GS) 6 including 950 men who underwent definitive treatment with surgery and 209 men who elected AS. The clinical and pathologic characteristics were documented for all subjects. Outcome measures and statistical analysis Men who underwent surgery were grouped according to their pathologic GS (upgraded was defined as GS ≥ 7; nonupgraded remained GS 6). Men who were enrolled in AS were also grouped according to their GS on subsequent surveillance biopsies. Statistical analyses were performed comparing the genotypes between the upgraded and nonupgraded groups. Results and limitations Overall, 31% and 34% of men were upgraded in the surgery and AS cohorts, respectively. Three iCOGS SNPs were significantly associated with the risk of upgrading in the surgical cohort. After correction for multiple testing, only rs11568818 on chromosome 11q22 remained significantly associated with upgrading. Assessment of this allele in the AS cohort reveals that it was present at noteworthy higher frequencies in men with high-grade disease on surveillance biopsies compared with nonupgraded men (p = 0.003). This study was primarily limited by the homogeneous patient population. Conclusions This is the first report of a SNP on chromosome 11q22 associated with higher grade disease in a surgical cohort that is also validated for eventual upgrading in a prospective AS cohort. Patient summary We examined the relationship between a group of genetic markers and prostate cancer (PCa) aggressiveness in a group of patients who underwent surgery for PCa and a group of patients who were enrolled in active surveillance. We found that these genetic markers helped predict which patients had more aggressive disease in both groups.

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Section: Introductionmentioning

confidence: 99%

Associations Between iCOGS Single Nucleotide Polymorphisms and Upgrading in Both Surgical and Active Surveillance Cohorts of Men with Prostate Cancer

et al. 2016

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“…Table S5 and Table S6 list the genes and variants, respectively, residing within the 10-Mb region of RNO7 centered on Myc . The 8q24 locus is pleiotropic with respect to its influence on disease susceptibility and has been associated with multiple cancer types in addition to breast cancer, including ovarian, prostate, colorectal, and bladder cancers (Braem et al 2011; Ishak and Giri 2011; Theodoratou et al 2012; Ma et al 2013; Sur et al 2013). Ept7 , a QTL that impacts development of E2-induced pituitary tumors in (BNxACI)F2 rats, has been mapped to the same region of RNO7 as Emca4 (Shull et al 2007; Kurz et al 2014).…”

Section: Resultsmentioning

confidence: 99%

Validation of Six Genetic Determinants of Susceptibility to Estrogen-Induced Mammary Cancer in the Rat and Assessment of Their Relevance to Breast Cancer Risk in Humans

Colletti

Leland-Wavrin

Kurz

et al. 2014

G3 Genes|Genomes|Genetics

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When treated with 17β-estradiol, female ACI rats (Rattus norvegicus) rapidly develop mammary cancers that share multiple phenotypes with luminal breast cancers. Seven distinct quantitative trait loci that harbor genetic determinants of susceptibility to 17β-estradiol−induced mammary cancer have been mapped in reciprocal intercrosses between susceptible ACI rats and resistant Brown Norway (BN) rats. A panel of unique congenic rat strains has now been generated and characterized to confirm the existence of these quantitative trait loci, designated Emca3 through Emca9, and to quantify their individual effects on susceptibility to 17β-estradiol−induced mammary cancer. Each congenic strain carries BN alleles spanning an individual Emca locus, introgressed onto the ACI genetic background. Data presented herein indicate that BN alleles at Emca3, Emca4, Emca5, Emca6, and Emca9 reduce susceptibility to 17β-estradiol−induced mammary cancer, whereas BN alleles at Emca7 increase susceptibility, thereby confirming the previous interval mapping data. All of these Emca loci are orthologous to regions of the human genome that have been demonstrated in genome-wide association studies to harbor genetic variants that influence breast cancer risk. Moreover, four of the Emca loci are orthologous to loci in humans that have been associated with mammographic breast density, a biomarker of breast cancer risk. This study further establishes the relevance of the ACI and derived congenic rat models of 17β-estradiol−induced mammary cancer for defining the genetic bases of breast cancer susceptibility and elucidating the mechanisms through which 17β-estradiol contributes to breast cancer development.

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“…27 When genetic correction was applied to a cohort of African-American men, the same PSA-SNPs yielded different results: genetic correction prevented no unnecessary biopsies, but could have been used to avoid delaying necessary biopsies in 30% of patients 43 . The racial differences in genetic correction are intriguing, as it is known that African-American men are significantly more likely to develop more advanced stage disease and have twice the PC-specific mortality than men of European ancestry 31, 44–47 . Genetically-corrected PSA levels in both European and African Americans may allow physicians to more accurately gauge the risk of PC and thus avoid unnecessary and/or delays in diagnosis 48 .…”

Section: Genetic Variants and Psa Screeningmentioning

confidence: 99%

A genetic-based approach to personalized prostate cancer screening and treatment

Helfand

Catàlona²,

2015

Current Opinion in Urology

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Purpose Recent advances in sequencing technologies has allowed for the identification of genetic variants within germline DNA that can explain a significant portion of the genetic underpinnings of prostate cancer. Despite evidence suggesting that these genetic variants can be used for improved risk stratification, they have not yet been routinely incorporated into routine clinical practice. This review highlights their potential utility in prostate cancer screening. Recent Findings There are now almost 100 genetic variants, called single nucleotide polymorphisms (SNPs) that have been recently found to be associated with the risk of developing prostate cancer. In addition, some of these prostate cancer risk SNPs also have been found to influence PSA expression levels and potentially aggressive disease. Summary Incorporation of panels of prostate cancer risk SNPs into clinical practice offers potential to provide improvements in 1) patient selection for prostate cancer screening 2) PSA interpretation (e.g. by correcting for the presence of SNPs that influence PSA expression levels, 3) decision for biopsy (using PC-risk SNPs) and possibly the 4) decision for treatment. A proposed clinical algorithm incorporating these PC-risk SNPs is discussed.

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A Systematic Review of Replication Studies of Prostate Cancer Susceptibility Genetic Variants in High-Risk Men Originally Identified from Genome-Wide Association Studies

Cited by 43 publications

References 51 publications

Associations Between iCOGS Single Nucleotide Polymorphisms and Upgrading in Both Surgical and Active Surveillance Cohorts of Men with Prostate Cancer

Associations Between iCOGS Single Nucleotide Polymorphisms and Upgrading in Both Surgical and Active Surveillance Cohorts of Men with Prostate Cancer

Validation of Six Genetic Determinants of Susceptibility to Estrogen-Induced Mammary Cancer in the Rat and Assessment of Their Relevance to Breast Cancer Risk in Humans

A genetic-based approach to personalized prostate cancer screening and treatment

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