Cancer polygenic risk score

Patent metadata

Field	Value
Publication number	US-2019345566-A1
Application number	US-201916510800-A
Country	US
Kind code	A1
Filing date	Jul 12, 2019
Priority date	Jul 12, 2017
Publication date	Nov 14, 2019
Grant date	—

Abstract

The present disclosure relates to a method of determining a risk of developing breast cancer in a subject, the method comprising identifying whether at least 95 single nucleotide polymorphisms (SNPs) from Table A is present in a biological sample from the subject, wherein the presence of a risk allele of a SNP from Table A indicates that the subject has an increased risk of breast cancer, and wherein the presence of an alternative allele indicates that the subject has a decreased risk of breast cancer.

First claim

What is claimed is:

1 . A method of determining a risk of developing breast cancer in a subject, the method comprising:
identifying whether at least 95 single nucleotide polymorphisms (SNPs) from Table A are present in a biological sample from the subject; wherein the presence of a risk allele of a SNP from Table A indicates that the subject has an increased risk of breast cancer, and wherein the presence of an alternative allele indicates that the subject has a decreased risk of breast cancer.

2 . The method of claim 1 , further comprising calculating a polygenic risk score (PRS).

3 . The method of claim 2 , wherein the PRS is calculated by summing the weighted risk score associated with each SNP identified.

4 . The method of claim 1 , wherein identifying comprises measuring the presence of the at least 95 SNPs in the biological sample.

5 . The method of claim 2 , further comprising assigning the subject to a risk group based on the PRS.

6 . The method of claim 1 , further comprising an initial step of obtaining a biological sample from the subject.

7 . The method of claim 1 , wherein at least 100 SNPs are identified.

8 . The method of claim 1 , wherein at least 200 SNPs, or at least 500 SNPs, or at least 1000 SNPs, or at least 2000 SNPs, or at least 5000 SNPs, or at least 10,000 SNPs, or at least 20,000 SNPs, or at least 50,000 SNPs, or at least 75,000 SNPs, or at least 100,000 SNPs, or at least 500,000 SNPs, or at least 1,000,000 SNPs, or at least 2,000,000 SNPs, or at least 3,000,000 SNPs, or at least 4,000,000 SNPs, or at least 5,000,000 SNPs, or at least 6,000,000 SNPs are identified.

9 . The method of claim 1 , wherein the identified SNPs comprise the highest risk SNPs.

10 . The method of claim 1 , wherein the identified SNPs comprise one or more of rs10841443, rs2244608, rs7500448, rs2972146, rs2972146, and rs11057401.

11 . The method of claim 1 , further comprising initiating a treatment to the subject.

12 . The method of claim 11 , wherein the treatment is determined or adjusted according to the risk of breast cancer.

13 . The method of claim 1 , wherein identifying whether the SNP is present comprises sequencing at least part of a genome of one or more cells from the subject.

14 . The method of claim 1 , wherein the subject is a human.

15 . The method of claim 13 , wherein sequencing comprises whole genome sequencing.

16 . A method of identifying a risk of developing breast cancer in a subject and providing a treatment to the subject, the method comprising:
obtaining a biological sample from the subject; identifying whether at least one single nucleotide polymorphism (SNP) from Table A is present in the biological sample; wherein the presence of a risk allele of a SNP from Table A indicates that the subject has an increased risk of breast cancer; and initiating a treatment of breast cancer to the subject.

17 . A method of determining a risk of developing breast cancer in a subject, the method comprising:
determining the presence or absence of risk alleles associated with breast cancer; and calculating a polygenic risk score for the subject; wherein the presence of a risk allele indicates that the subject has an increased risk of breast cancer, and wherein the presence of an alternative allele indicates that the subject has a decreased risk of breast cancer.

18 . The method of claim 17 , wherein the polygenic risk score does not comprise alleles of BRCA-1 or BRCA-2.

19 . The method of claim 17 , wherein the polygenic risk score comprises odds ratios indicative of breast cancer.

20 . The method of claim 19 , wherein the polygenic risk score comprises odds ratios determined on a plurality of genetic loci.

21 . The method of claim 20 , wherein the polygenic risk score comprises odds ratios 1.5 or greater, or 1.75 or greater, or 2.0 or greater, or 2.25 or greater for the top 20% of the distribution.

22 . The method of claim 20 , wherein the polygenic risk score comprises odds ratios 1.5 or greater, or 1.75 or greater, or 2.0 or greater, or 2.25 or greater, or 2.5 or greater, or 2.75 or greater for the top 5% of the distribution.

23 . The method of claim 20 , wherein the polygenic risk score comprises odds ratios equal to or greater than provided in Table 45.

24 . The method of claim 17 , wherein the polygenic risk score is used to guide enhanced diagnostic strategies, optionally mammography, breast MRI, or breast ultrasound.

25 . The method of claim 17 , wherein the polygenic risk score is used to guide chemoprevention.

26 . The method of claim 17 , wherein the polygenic risk score is used to guide prophylactic breast surgery.

27 . The method of claim 17 , wherein the risk allele comprises one or more SNPs from Table A.

28 . A method of detecting single nucleotide polymorphisms (SNPs) in a subject, said method comprising:
detecting whether at least 95 SNPs from Table A are present in a biological sample from a subject by contacting the biological sample with a set of probes to each SNP and detecting binding of the probes, by amplifying genome regions comprising the SNPs using a set of amplification primers, or by sequencing genomic regions comprising or enriched for the SNPs.

29 . The method of claim 28 , wherein detecting whether at least 95 SNPs from Table A are present in the biological sample comprises detecting whether at least 200 SNPs, or at least 500 SNPs, or at least 1000 SNPs, or at least 2000 SNPs, or at least 5000 SNPs are present in the biological sample.

30 . A method of determining a polygenic risk score for (PRS) developing breast cancer in a subject, the method comprising:
selecting at least 95 single nucleotide polymorphisms (SNPs) from Table A; identifying whether the at least 95 SNPs are present in a biological sample from the subject; and calculating the polygenic risk score (PRS) based on the presence of the SNPs.

Assignees

• Massachusetts Gen Hospital

Inventors

• Khera Amit V
• Klarin Derek
• Kathiresan Sekar

Classifications

• G16B40/20

  Supervised data analysis · CPC title

• G16B20/20

  Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection · CPC title

• G16B20/00

  ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• G16H50/30

  for calculating health indices; for individual health risk assessment · CPC title