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Review
. 2016 Feb;12(4):503-13.
doi: 10.2217/fon.15.303. Epub 2016 Feb 1.

Quantifying the utility of single nucleotide polymorphisms to guide colorectal cancer screening

Mark A Jenkins  1 , Enes Makalic  1 , James G Dowty  1 , Daniel F Schmidt  1 , Gillian S Dite  1 , Robert J MacInnis  1   2 , Driss Ait Ouakrim  1 , Mark Clendenning  3 , Louisa B Flander  1 , Oliver K Stanesby  1 , John L Hopper  1 , Aung K Win  1 , Daniel D Buchanan  1   3
Affiliations
Review

Quantifying the utility of single nucleotide polymorphisms to guide colorectal cancer screening

Mark A Jenkins et al. Future Oncol. 2016 Feb.

Abstract

Aim: To determine whether single nucleotide polymorphisms (SNPs) can be used to identify people who should be screened for colorectal cancer.

Methods: We simulated one million people with and without colorectal cancer based on published SNP allele frequencies and strengths of colorectal cancer association. We estimated 5-year risks of colorectal cancer by number of risk alleles.

Results: We identified 45 SNPs with an average 1.14-fold increase colorectal cancer risk per allele (range: 1.05-1.53). The colorectal cancer risk for people in the highest quintile of risk alleles was 1.81-times that for the average person.

Conclusion: We have quantified the extent to which known susceptibility SNPs can stratify the population into clinically useful colorectal cancer risk categories.

Keywords: cancer screening; colorectal cancer; risk prediction; single nucleotide polymorphisms.

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Conflict of interest statement

Financial & competing interests disclosure This work was supported by Centre for Research Excellence grant APP1042021 and Program grant APP1074383 from the National Health and Medical Research Council (NHMRC), Australia. MA Jenkins is a NHMRC Senior Research Fellow. AK Win is a NHMRC Early Career Fellow. JL Hopper is a NHMRC Senior Principal Research Fellow. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. The simulated distribution of risk alleles for 1,000,000 people with a history of colorectal cancer (red) and 1,000,000 people without a history of colorectal cancer (blue); and the cumulative risk of colorectal cancer to age 70 years for the number of risk alleles for an Australian (square) and USA (circle) population.
SNP: Single nucleotide polymorphism.
<b>Figure 2.</b>
Figure 2.. Australian risks of colorectal cancer (males and females combined) by age category, family history of colorectal cancer (first-degree relative) and by number of risk alleles.
(A) Cumulative risks to age 70 years with highest and lowest quintiles for number of risk alleles. (B) Cumulative risks to age 70 years with highest and lowest deciles for number of risk alleles. (C) 5-year risks with highest and lowest quintiles for number of risk alleles. (D) 5-year risks with highest and lowest deciles for number of risk alleles.
<b>Figure 3.</b>
Figure 3.. USA risks of colorectal cancer (males and females combined) by age category, family history of colorectal cancer (first-degree relative) and by number of risk alleles.
(A) Cumulative risks to age 70 years with highest and lowest quintiles for number of risk alleles. (B) Cumulative risks to age 70 with highest and lowest deciles for number of risk alleles. (C) 5-year risks with highest and lowest quintiles for number of risk alleles. (D) 5-year risks with highest and lowest deciles for number of risk alleles.
See this image and copyright information in PMC

References

    1. Vasen HF, Van Der Meulen-De Jong AE, De Vos Tot Nederveen Cappel WH, Oliveira J, Group EGW. Familial colorectal cancer risk: ESMO clinical recommendations. Ann. Oncol. 2009;20(Suppl. 4):51–53. - PubMed
    1. Tenesa A, Dunlop MG. New insights into the aetiology of colorectal cancer from genome-wide association studies. Nat. Rev. Genet. 2009;10(6):353–358. - PubMed

    2. • Provided an estimation of the potential number single nucleotide polymorphisms (SNPs) to explain the remaining excess familial risk for colorectal cancer.

    1. Welter D, Macarthur J, Morales J, et al. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res. 2014;42:D1001–D1006. - PMC - PubMed
    1. Whiffin N, Dobbins SE, Hosking FJ, et al. Deciphering the genetic architecture of low-penetrance susceptibility to colorectal cancer. Hum. Mol. Genet. 2013;22(24):5075–5082. - PMC - PubMed
    1. Zhang B, Jia W-H, Matsuda K, et al. Large-scale genetic study in east Asians identifies six new loci associated with colorectal cancer risk. Nat. Genet. 2014;46(6):533–542. - PMC - PubMed