A genome-wide association screen identifies regions on chromosomes 1q25 and 7p21 as risk loci for sporadic prostate cancer

Nam, Robert K.; Zhang, W W; Loblaw, D.A.; Klotz, Laurence; Trachtenberg, John; Jewett, Michael A.S.; Stanimirovic, Aleksandra; Davies, Teresa; Toi, Ants; Venkateswaran, Vasundara; Sugar, Linda; Siminovitch, Kathy; Narod, Steven A.

doi:10.1038/sj.pcan.4501010

Cited by 32 publications

(21 citation statements)

References 20 publications

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“…A genome-wide association study of 3090 sporadic prostate patients and controls was undertaken by Nam et al [6]. The study involved 40 prostate cancer patients and 40 controls and found that there were a total of 237 single nucleotide polymorphisms (SNPs) associated with prostate cancer.…”

Section: Prostate Cancermentioning

confidence: 99%

Evidence that Natural Immunity to Breast Cancer and Prostate Cancer Exists in the Majority of Their Risk Populations Is Predicted by a Novel, Inherently Saturated, Ordered Mutation Model

Kramer

2007

Computational and Mathematical Methods in Medicine

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The series of ordered mutations that cause a specific cell to become cancerous is modeled so that the fraction of a risk population (e.g. White men) that has developed a specific cancer (e.g. melanoma) at any age can be calculated. The saturated model constructed and solved here is isomorphic to the physical model describing an ordered chain of radioactive nuclei decays with the exception that it allows for the possibility that a fraction of a risk population may be immune to developing a specific cancer.The simplest model developed here depends on only three independent parameters: the number of ordered mutations necessary for a cell to become cancerous, the fraction of the risk population that is immune to developing a specific cancer and the average time between mutations (a time defined as the mutation lifetime). The values of these independent parameters are determined by fitting the model's cancer incidence function to the cancer incidence data.This model was applied to five widely different cancers: melanoma, pancreatic cancer, female breast cancer, non-Hodgkin lymphoma and prostate cancer. The modeling predicts that all White males in the USA are vulnerable to developing melanoma, five-ordered mutations are required to develop it and the mutation lifetime is 48.3 years. By contrast, the modeling predicts that 80.7% of White females in the USA are immune to developing melanoma, three-ordered mutations are required to develop it and the mutation lifetime is 78.9 years. Remarkably, it was also found that about 70% of females are immune to developing breast cancer and about 70% of males are immune to developing prostate cancer, predictions that fit in with the experimental evidence of cancer immunosurveillance and immunoediting.Clearly, different risk populations can develop the same cancer through different pathways. Delineating the mechanism underlying the prevalence of immunity to specific cancers in specific risk populations should become a research priority. Finding ways of blocking or repairing cellular mutations and/or destroying mutated, potentially cancerous cells would prevent cancers from developing altogether and eliminate a major cause of mortality.1. The saturated, ordered, mutation model of cancer developmentResearch data suggests that a cancerous cell results from an ordered series of random mutations. A potentially cancerous cell spontaneously mutates from one mutation state to another in a definite order until the final mutation causes the cell to become cancerous. Thus, for example, a normal, unmutated cell can only mutate into the first mutation state and no other and cells that are in the first mutation state can only mutate into the second mutation state and no other, etc. It is assumed that the characteristics of the cell in each mutation state are unique and different from the characteristics of the cell in every other mutation state. It is also assumed that a specific cancer results from an ordered series of mutations of a single cell of a specific organ.Clearly, the number of mutatio...

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Section: Prostate Cancermentioning

confidence: 99%

Evidence that Natural Immunity to Breast Cancer and Prostate Cancer Exists in the Majority of Their Risk Populations Is Predicted by a Novel, Inherently Saturated, Ordered Mutation Model

Kramer

2007

Computational and Mathematical Methods in Medicine

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“…It is encoded by the GAS5 gene on 1q25, a PCA-associated locus [62]. In proliferating cells, GAS5 translation is regulated by the mechanistic target of rapamycin (mTOR) pathway and the nonsense-mediated decay (NMD) pathway.…”

Section: Long Non-coding Rnas and Prostate Cancermentioning

confidence: 99%

Current Insights into Long Non-Coding RNAs (LncRNAs) in Prostate Cancer

Smolle

Bauernhofer

Pummer

et al. 2017

IJMS

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The importance of long non-coding RNAs (lncRNAs) in the pathogenesis of various malignancies has been uncovered over the last few years. Their dysregulation often contributes to or is a result of tumour progression. In prostate cancer, the most common malignancy in men, lncRNAs can promote castration resistance, cell proliferation, invasion, and metastatic spread. Expression patterns of lncRNAs often change during tumour progression; their expression levels may constantly rise (e.g., HOX transcript antisense RNA, HOTAIR), or steadily decrease (e.g., downregulated RNA in cancer, DRAIC). In prostate cancer, lncRNAs likewise have diagnostic (e.g., prostate cancer antigen 3, PCA3), prognostic (e.g., second chromosome locus associated with prostate-1, SChLAP1), and predictive (e.g., metastasis-associated lung adenocarcinoma transcript-1, MALAT-1) functions. Considering their dynamic role in prostate cancer, lncRNAs may also serve as therapeutic targets, helping to prevent development of castration resistance, maintain stable disease, and prohibit metastatic spread.

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“…Examples of non-coding genes with differentially expressed transcripts found in this dataset include the lincRNAs PART1 (prostate androgen-regulated transcript 1) [20], MEG3 [21], the PVT1 oncogene, located in the 8q24 susceptibility region [22], and the testis-specific lincRNA TTTY10, which has been previously shown to be expressed in prostate [23]. Other ncRNAs include the small nucleolar RNA host gene 1 (SNHG1) which has been suggested as a useful biomarker for prostate cancer progression [24], as well as GAS5, located in the 1q25 risk loci [25]. Furthermore, three pseudogenes are found differentially expressed in this dataset including EEF1DP3, located in a region previously found to be a focal deletion in metastatic tumors [26] and the Y-linked pseudogene PRKY, which has been found expressed in prostate cancer cell lines [27].…”

Section: Resultsmentioning

confidence: 99%

Transcriptome-Wide Detection of Differentially Expressed Coding and Non-Coding Transcripts and Their Clinical Significance in Prostate Cancer

Erho

Buerki

Triche

et al. 2012

Journal of Oncology

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Prostate cancer is a clinically and biologically heterogeneous disease. Deregulation of splice variants has been shown to contribute significantly to this complexity. High-throughput technologies such as oligonucleotide microarrays allow for the detection of transcripts that play a role in disease progression in a transcriptome-wide level. In this study, we use a publicly available dataset of normal adjacent, primary tumor, and metastatic prostate cancer samples (GSE21034) to detect differentially expressed coding and non-coding transcripts between these disease states. To achieve this, we focus on transcript-specific probe selection regions, that is, those probe sets that correspond unambiguously to a single transcript. Based on this, we are able to pinpoint at the transcript-specific level transcripts that are differentially expressed throughout prostate cancer progression. We confirm previously reported cases and find novel transcripts for which no prior implication in prostate cancer progression has been made. Furthermore, we show that transcript-specific differential expression has unique prognostic potential and provides a clinically significant source of biomarker signatures for prostate cancer risk stratification. The results presented here serve as a catalog of differentially expressed transcript-specific markers throughout prostate cancer progression that can be used as basis for further development and translation into the clinic.

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A genome-wide association screen identifies regions on chromosomes 1q25 and 7p21 as risk loci for sporadic prostate cancer

Cited by 32 publications

References 20 publications

Evidence that Natural Immunity to Breast Cancer and Prostate Cancer Exists in the Majority of Their Risk Populations Is Predicted by a Novel, Inherently Saturated, Ordered Mutation Model

Evidence that Natural Immunity to Breast Cancer and Prostate Cancer Exists in the Majority of Their Risk Populations Is Predicted by a Novel, Inherently Saturated, Ordered Mutation Model

Current Insights into Long Non-Coding RNAs (LncRNAs) in Prostate Cancer

Transcriptome-Wide Detection of Differentially Expressed Coding and Non-Coding Transcripts and Their Clinical Significance in Prostate Cancer

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