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Method for indicating a presence or non-presence of prostate cancer in individuals with particular characteristics

A prostate cancer, individual technology, applied in the field of prostate cancer in men, to improve the detection of prostate cancer and specific aggressive forms of prostate cancer, can solve the problems of low availability of predictive models and difficult identification

Pending Publication Date: 2019-10-25
PHADIA A B (SE)
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, identification of aPCa is difficult, in part because larger cohorts are required to provide a sufficient number of cases and controls in developing statistical models
Therefore, the availability of predictive models for aPCa is low

Method used

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  • Method for indicating a presence or non-presence of prostate cancer in individuals with particular characteristics
  • Method for indicating a presence or non-presence of prostate cancer in individuals with particular characteristics
  • Method for indicating a presence or non-presence of prostate cancer in individuals with particular characteristics

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 6

[0096] Tables 5, 6 and 7 of Example 6 show the performance of PCaGS-specific PSA cutoffs to match PSA = 3 ng / ml as used in the general population for detection of aggressive prostate cancer, respectively, as used in the general population for detection of PSA = 3 ng / ml performance for prostate cancer, and PSA = 4 ng / mL performance for prostate cancer detection. Therefore, these values ​​can be set as surrogate PSA cutoffs for detection of PCa in these specific PCaGS.

[0097] The PCaGS of Example 6 includes:

[0098] - HOXB13-positive, ie rs138213197-positive individuals (PCaGS_ex2),

[0099] - Defines individuals (PCaGS_61) whose PcaGS with risk scores (rs16901979, rs7818556, rs12793759, rs138213197) have a value greater than 0.7

[0100] - Individuals with a value greater than 0.7 (PCaGS_62) defining a subgroup of risk scores containing (rs16901979, rs7818556, rs12793759, rs138213197, rs16860513, rs7106762)

[0101] - Individuals (PCaGS_63) with a PcaGS risk score greater...

Embodiment 1

[0199] In the first example, the PCaGS_ex1 subgroup is defined as follows:

[0200] PCaGS_ex1 members have one or both of the following:

[0201] Homozygous risk allele carriers for SNPs with an odds ratio of 1.2 to 2

[0202] Heterozygous risk allele carrier for a SNP with an odds ratio >2

[0203] The data set used in this example included 4384 individuals from the STHLM3 study, and for each individual, genotypes of 254 different SNPs (List 2 above), protein biomarker concentrations (total PSA, free total PSA, Concentrations of free intact PSA, hK2, MSMB, and MIC1), family history, age, prostate volume, and digital rectal results were known. 308 individuals (7%) were members of the PCaGS subgroup. Of these 308, 60 (19%) had Gleason 7+ cancer.

[0204] The cohort of 4384 did not include information on ethnic background, but was a cohort of randomly selected men aged 50-70 at the time with a residential address in Stockholm. Sweden is a multicultural society. In 2012, ab...

Embodiment 2

[0222] In a second example, the same data set as in Example 1 was used, and the PCaGS_ex2 subgroup was defined as individuals carrying at least one risk allele of rs138213197 (HOXB13). The distribution of individuals with PSA values ​​greater than 4.0 ng / mL is shown in Table 3:

[0223] benign Gleason score of 6 or higher Gleason score of 7 or higher PCaGS_ex2 group 7 26 16 Non-PCaGS_ex2 group 1151 830 439

[0224] table 3.

[0225] This means that for individuals in the PCaGS_ex2 subgroup with a PSA value greater than 4.0 ng / mL, the probability of having prostate cancer (Gleason score 6 or higher) is approximately 79% and having aggressive prostate cancer (Gleason score 7 or higher) is approximately 48% of the time. In contrast, individuals who were not members of the PCaGS_ex2 subgroup and had a PSA value greater than 4.0 had a 42% probability of prostate cancer and a 22% probability of invasive prostate cancer. In this particular case ...

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Abstract

The present invention relates generally to the detection and identification of various forms of genetic markers, and various forms of proteins, which have the potential utility as diagnostic markers.By determining the level of a plurality of biomarkers and genetic markers in a patient sample, and combining the obtained values according to a predefined formula, it is possible to determine if it islikely that the patient suffers from prostate cancer or aggressive prostate cancer. The method is improved by distinguishing between genetic subpopulations with a particularly high risk for prostatecancer or aggressive prostate cancer.

Description

[0001] field of invention [0002] The present invention generally relates to the detection and identification of various forms of genetic markers and various forms of proteins that have potential utility as diagnostic markers. In particular, the present invention relates to the simultaneous use of multiple diagnostic markers for improved detection of prostate cancer and, in particular, aggressive forms of prostate cancer. More specifically, the present invention relates to the simultaneous use of multiple diagnostic markers for improved detection of prostate cancer in men with specific genetic characteristics. [0003] Background of the invention [0004] Measurement of serum prostate-specific antigen (PSA) is widely used for screening and early detection of prostate cancer (PCa). As described in the public report "Polygenic Risk Score Improves Prostate Cancer Risk Prediction: Results from the Stockholm-1 Cohort Study" by Markus Aly and co-authors published in EUROPEAN UROLOG...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886
CPCC12Q1/6886C12Q2600/156C12Q2600/118C12Q2600/158G16B40/00G16B10/00G16B5/00G16B15/00
Inventor H.格伦贝格
Owner PHADIA A B (SE)