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Methods for assessing risk of developing colorectal cancer

A colorectal cancer, risk technology, applied in the direction of biochemical equipment and methods, microbial measurement/testing, instruments, etc., can solve the problem of complex genetic susceptibility to colorectal cancer

Pending Publication Date: 2018-12-21
UNIVERSITY OF MELBOURNE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, genetic susceptibility to hereditary colorectal cancer is complex and involves multiple variants and genes

Method used

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  • Methods for assessing risk of developing colorectal cancer
  • Methods for assessing risk of developing colorectal cancer
  • Methods for assessing risk of developing colorectal cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0222] Example 1 - SNPs indicative of colorectal cancer risk

[0223] Fifty-four SNPs associated with colorectal cancer in a European population were identified. Among them, 4 SNPs within 11q12.2 (rs174537, rs4246215, rs174550, and rs1535) are fully related and can be represented by common haplotypes (herein referred to as 11q12.2 haplotypes). Two SNPs within 19q13.2 (rs1800469 and rs2241714) are perfectly related and can be represented by common haplotypes (referred to herein as 19q13.2 haplotypes). One SNP is located on the X chromosome (rs5934683) and was not included in colorectal cancer risk simulations for both males and females. Two SNPs (rs6687758 and rs6691170) within 1q41 are in linkage disequilibrium. Therefore, rs6691170 was excluded. Three SNPs (rs10505477, rs6983267 and rs7014346) within 8q24.21 had a D prime of 1.0. Therefore, rs10505477 and rs7014346 were excluded. The D prime of two SNPs (rs1035209 and rs11190164) within 10q24.2 was 0.9. Therefore, rs10...

Embodiment 2

[0230] Example 2 - Risk Allele Simulation

[0231] Simulations were performed using the software PLINK (Purcell et al., 2007) (http: / / pngu.mgh.harvard.edu / purcell / plink / ) to determine the cumulative number of risk alleles of SNPs that differentiate colorectal cancer cases from controls ability, and to estimate colorectal cancer risk as a function of the number of risk alleles.

[0232] A population of 1,000,000 people with colorectal cancer (cases) and 1,000,000 people without colorectal cancer (controls) was simulated. The distribution of SNP risk alleles for the simulated population matched the reported risk allele frequencies and per-allelic odds ratios for the colorectal cancer association. A simple risk model was assumed in this assessment in which the association of each SNP with colorectal cancer was independent. In this analysis, it was also assumed that the odds ratios for colorectal cancer reported by each SNP apply to both males and females and vary with age.

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Embodiment 3

[0248] Example 3 - Classification of subjects according to risk of colorectal cancer

[0249] Simulations were used to quantify the utility of a panel of 45 risk-associated SNPs to classify persons according to their colorectal cancer risk. People at the ends of the risk allele spectrum were more likely to develop colorectal cancer (high end) or less likely to develop colorectal cancer (low end). Because the total variation in risk associated with these SNPs across the population can explain about a quarter of the total FRR, the predictive strength of the SNP profile increases if family history of colorectal cancer is also considered. Considering that for the bottom 20% of the population (for the number of risk alleles for these SNPs), the strength of the association with colorectal cancer was roughly inverse to the increased risk associated with the remaining FRR, with a family history of colorectal cancer, but at these Persons in the lowest quintile of the population for ...

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Abstract

The present disclosure relates to methods and systems for assessing the risk of a human subject for developing colorectal cancer. These methods may be combined with the subjects clinical risk to improve risk analysis. Such methods may be used to assist decision making about appropriate colorectal cancer screening regimens.

Description

technical field [0001] The present disclosure relates to methods and systems for assessing the risk of colorectal cancer in a human subject. These methods can be combined with subject clinical risk to improve risk analysis. These methods can be used to aid in decision making regarding appropriate colorectal cancer screening regimens. Background technique [0002] Colorectal cancer screening programs advocate testing of individuals in an apparently healthy population to identify individuals with premalignant or early-stage colorectal cancer so that they may benefit from prevention or early treatment. Screening tests may include fecal occult blood tests and colonoscopy. Fecal occult blood test-based screening reduces colorectal mortality by 15% to 25% in average risk populations (Hewitson et al., 2007). Endoscopic screening reduces mortality by 30% to 40% (Brenner et al., 2014). [0003] Screening large populations can be costly. Ideally, decisions about who should be scr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886C40B40/06
CPCC40B40/06C12Q2600/156C12Q1/6886C12Q1/68G16B20/20
Inventor 马克·詹金斯丹尼尔·布坎南约翰·L·霍珀
Owner UNIVERSITY OF MELBOURNE
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