US 11,773,448 B2
Methods for assessing risk of developing colorectal cancer
Mark Jenkins, Parkville (AU); Daniel Buchanan, Parkville (AU); and John L. Hopper, Parkville (AU)
Assigned to THE UNIVERSITY OF MELBOURNE, Parkville (AU)
Appl. No. 16/74,032
Filed by The University of Melbourne, Parkville (AU)
PCT Filed Jan. 27, 2017, PCT No. PCT/AU2017/050066
§ 371(c)(1), (2) Date Jul. 30, 2018,
PCT Pub. No. WO2017/127893, PCT Pub. Date Aug. 3, 2017.
Claims priority of application No. 2016900254 (AU), filed on Jan. 28, 2016; and application No. 2016903246 (AU), filed on Aug. 16, 2016.
Prior Publication US 2019/0161802 A1, May 30, 2019
Int. Cl. C12Q 1/6886 (2018.01); G16B 20/20 (2019.01); C40B 40/06 (2006.01)
CPC C12Q 1/6886 (2013.01) [C40B 40/06 (2013.01); G16B 20/20 (2019.02); C12Q 2600/156 (2013.01)] 16 Claims
 
1. A method of prophylactically treating a human subject determined to have an increased risk for colorectal cancer, the method comprising:
(i) determining a risk score for the human subject of developing colorectal cancer by the following steps:
a) obtaining the odds ratio (OR) of association with colorectal cancer of 45 single nucleotide polymorphisms (SNPs) consisting of SNPs rs72647484, rs10911251, one of rs6687758 or rs6691170, rs11903757, rs812481, rs35360328, rs10936599, rs3987, rs35509282, rs647161, rs1321311, rs16892766, one of rs6983267 or rs10505477 or rs7014346, rs719725, rs10904849, rs10795668, rs704017, one of rs11190164 or rs1035209, rs12241008, one of rs174537 or rs4246215 or rs174550 or rs1535, rs3824999, rs3802842, rs3217810, rs3217901, rs10774214, rs11169552, rs7136702, rs3184504, rs59336, rs73208120, rs1957636, rs4444235, rs11632715, rs16969681, rs9929218, rs16941835, rs744166, rs4939827, rs10411210, one of rs1800469 or rs2241714, rs2423279, rs4813802, rs961253, rs6066825, and rs4925386;
b) obtaining the identity of alleles present in the genome of a human subject at a panel of SNPs consisting of the 45 SNPs;
c) determining an adjusted risk score for each of the 45 SNPs of the human subject, where:
(i) if two major alleles are present at the SNP, then the adjusted risk score for the SNP is 1/μ,
(ii) if one major and one minor allele are present at the SNP, then the adjusted risk score for the SNP is OR/μ,
(iii) if two minor alleles are present at the SNP, then the adjusted risk score for the SNP is OR2/μ, and
(iv) if the genotype is missing for the SNP, then the adjusted risk score for the SNP is 1,
where μ=(1−p)2+2p(l−p)OR+p2OR2, wherein OR is the odds ratio of a minor allele at the given SNP and p is the frequency of the minor allele;
d) multiplying together the adjusted risk score for each of the 45 SNPs of the human subject to produce a genetic risk score of the human subject;
e) obtaining a clinical risk assessment of the human subject;
f) combining the clinical risk assessment of the human subject with the genetic risk score of the human subject; and
g) producing a number which represents the risk of the human subject developing colorectal cancer relative to the average risk of developing colorectal cancer in the population to which the human subject belongs;
(ii) identifying the human subject as at increased risk for colorectal cancer based on the risk score; and
(iii) prophylactically treating the human subject with a nonsteroidal anti-inflammatory drug.