Quantifying the utility of single nucleotide polymorphisms to guide colorectal cancer screening
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.
Papers of special note have been highlighted as: • of interest
References
- 1 . Familial colorectal cancer risk: ESMO clinical recommendations. Ann. Oncol. 20(Suppl. 4), 51–53 (2009).
- 2 . New insights into the aetiology of colorectal cancer from genome-wide association studies. Nat. Rev. Genet. 10(6), 353–358 (2009). • Provided an estimation of the potential number single nucleotide polymorphisms (SNPs) to explain the remaining excess familial risk for colorectal cancer.
- 3 The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res 42, D1001–D1006 (2014).
- 4 Deciphering the genetic architecture of low-penetrance susceptibility to colorectal cancer. Hum. Mol. Genet. 22(24), 5075–5082 (2013).
- 5 Large-scale genetic study in east Asians identifies six new loci associated with colorectal cancer risk. Nat. Genet. 46(6), 533–542 (2014).
- 6 Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat. Genet. 45(4), 353–361, 361e1–361e2 (2013).
- 7 A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat. Genet. 46(10), 1103–1109 (2014).
- 8 Cumulative impact of common genetic variants and other risk factors on colorectal cancer risk in 42,103 individuals. Gut 62(6), 871–881 (2013). • First study attempting to calculate risk score for colorectal cancer from measured SNP data.
- 9 PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81(3), 559–575 (2007).
- 10 PLINK. http://pngu.mgh.harvard.edu/purcell/plink/.
- 11 . Comprehensive evaluation of the impact of 14 genetic variants on colorectal cancer phenotype and risk. Am. J. Epidemiol. 175(1), 1–10 (2012).
- 12 Australian Institute of Health and Welfare (AIHW). Australian Cancer Incidence and Mortality (ACIM) books: Colorectal cancer (also called bowel cancer) Canberra: AIHW (2015). www.aihw.gov.au/acim-books/.
- 13 SEER Cancer Statistics Review, 1975–2012, National Cancer Institute, Bethesda, MD, USA. http://seer.cancer.gov/csr/1975_2012.
- 14 . Polygenic inheritance of breast cancer: Implications for design of association studies. Genet. Epidemiol. 25(3), 190–202 (2003).
- 15 Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer. Gastroenterology 146(5), 1208–1211, e1201–e1205 (2014).
- 16 . A systematic review and meta-analysis of familial colorectal cancer risk. Am. J. Gastroenterol. 96(10), 2992–3003 (2001).
- 17 Genome-wide association study identifies a new SMAD7 risk variant associated with colorectal cancer risk in east Asians. Int. J. Cancer 135(4), 948–955 (2014).
- 18 Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk. Nat. Genet. 44(7), 770–776 (2012).
- 19 Refinement of the associations between risk of colorectal cancer and polymorphisms on chromosomes 1q41 and 12q13.13. Hum. Mol. Genet. 21(4), 934–946 (2012).
- 20 . Association of 8q24.21 loci with the risk of colorectal cancer: a systematic review and meta-analysis. J. Gastroenterol. Hepatol. 26(10), 1475–1484 (2011).
- 21 Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer. PLoS Genet. 7(6), e1002105 (2011).
- 22 A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer. Sci. Rep. 5, 10442 (2015).
- 23 Meta-analysis of new genome-wide association studies of colorectal cancer risk. Hum. Genet. 131(2), 217–234 (2012).
- 24 Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis. Hum. Mol. Genet. 23(17), 4729–4737 (2014).
- 25 Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33. Nat. Genet. 42(11), 973–977 (2010).
- 26 Identification of genetic susceptibility loci for colorectal tumors in a genome-wide meta-analysis. Gastroenterology 144(4), 799–807 e724 (2013).
- 27 Genome-wide association study of colorectal cancer identifies six new susceptibility loci. Nat. Commun. 6, 7138 (2015).
- 28 A colorectal cancer susceptibility new variant at 4q26 in the Spanish population identified by genome-wide association analysis. PLoS ONE 9(6), e101178 (2014).
- 29 A novel colorectal cancer risk locus at 4q32.2 identified from an international genome-wide association study. Carcinogenesis 35(11), 2512–2519 (2014).
- 30 Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancer. Nat. Genet. 45(2), 191–196 (2013).
- 31 A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3. Nat. Genet. 40(5), 623–630 (2008).
- 32 Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat. Genet. 39(8), 989–994 (2007).
- 33 A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat. Genet. 39(8), 984–988 (2007).
- 34 Characterization of 9p24 risk locus and colorectal adenoma and cancer: gene-environment interaction and meta-analysis. Cancer Epidemiol. Biomarkers Prev. 19(12), 3131–3139 (2010).
- 35 Common genetic variants at the MC4R locus are associated with obesity, but not with dietary energy intake or colorectal cancer in the Scottish population. Int. J. Obes. (Lond.) 33(2), 284–288 (2009).
- 36 Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer. PLoS Genet. 7(6), e1002105 (2011).
- 37 Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer. Nat. Genet. 40(12), 1426–1435 (2008).
- 38 An analysis of genetic factors related to risk of inflammatory bowel disease and colon cancer. Cancer Epidemiol. 38(5), 583–590 (2014).
- 39 A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk. Nat. Genet. 39(11), 1315–1317 (2007).
- 40 A model to determine colorectal cancer risk using common genetic susceptibility loci. Gastroenterology 148(7), 1330.e14–1339.e14 (2015). • Most recent and largest study to calculate risk score for colorectal cancer from measured SNP data.
- 41 Estimating the heritability of colorectal cancer. Hum. Mol. Genet. 23(14), 3898–3905 (2014).
- 42 . Screening for colorectal cancer using the faecal occult blood test, Hemoccult. Cochrane Database Syst. Rev. (1), CD001216 (2007).
- 43 . Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of randomised controlled trials and observational studies. BMJ 348, g2467 (2014).
- 44 Screening practices of unaffected people at familial risk of colorectal cancer. Cancer Prev. Res. (Phila.) 5(2), 240–247 (2012).