Skip to main content
SpringerLink
Log in

The Colon Cancer Family Registry Cohort

  • Chapter
  • First Online:
Hereditary Colorectal Cancer

Abstract

The Colon Cancer Family Registry Cohort (CCFRC) was established in 1997 for NIH stated purposes of research on the genetic and environmental aetiology of colorectal cancer and the identification of individuals who, because of their high risk, could benefit from preventive strategies. A case-control-family design was utilised to enhance genetic as well as environmental research, including gene discovery and characterisation, and to evaluate modifiers of genetic risk. The 42,489 study participants from 15,049 families were recruited between 1998 and 2012 in the USA, Canada, Australia and New Zealand including recently diagnosed colorectal cancer cases from population-based cancer registries, controls from population-based sources, patients from family cancer clinics with a strong family history of colorectal cancer or young-onset disease and their relatives, both those affected and those unaffected by cancer. At baseline, participants provided a blood/buccal wash sample and access to medical records and tumour specimens and completed a detailed risk factor questionnaire (height, weight, alcohol use, smoking, physical activity, medication use, diet, screening, cancer diagnoses, detailed family history of cancer). Every 4–5 years after baseline, all population-based case-families and clinic-based families were followed up for updates on their personal and family history of cancer as well as history of surgery, cancer screening and some risk factors. The total follow-up of 37,436 participants covers 339,000 person-years (277,000 via direct survey of participants and 62,000 via interview of participating relatives). During follow-up, 824 (2.2%) participants were diagnosed with a colorectal cancer and 3582 (9.5%) were diagnosed with a non-colorectal cancer. Participants have had germline testing for major colorectal cancer genetic syndromes (Lynch syndrome and MUTYH) and undergone genome-wide SNP genotyping. Colorectal cancer cases were tested for major somatic alterations, for clinically relevant molecular subtypes, including tumour microsatellite instability, mismatch repair protein loss in immunohistochemistry, the common somatic KRAS and BRAF variants, MLH1 methylation and CpG island methylator phenotype (CIMP). Data and biospecimens are available for collaborative research and have been utilised for over 400 publications and approximately 300 projects (53% are external investigator-driven projects) – see http://www.coloncfr.org/.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86. https://doi.org/10.1002/ijc.29210.

    Article  CAS  PubMed  Google Scholar 

  2. Newcomb PA, Baron J, Cotterchio M, Gallinger S, Grove J, Haile R, et al. Colon Cancer Family Registry: an international resource for studies of the genetic epidemiology of colon cancer. Cancer Epidemiol Biomark Prev. 2007;16(11):2331–43. https://doi.org/10.1158/1055-9965.epi-07-0648.

    Article  Google Scholar 

  3. Kolonel LN, Henderson BE, Hankin JH, Nomura AM, Wilkens LR, Pike MC, et al. A multiethnic cohort in Hawaii and Los Angeles: baseline characteristics. Am J Epidemiol. 2000;151(4):346–57.

    Article  CAS  PubMed  Google Scholar 

  4. Ireland P, Jolley D, Giles G, O’Dea K, Powles J, Rutishauser I, et al. Development of the Melbourne FFQ: a food frequency questionnaire for use in an Australian prospective study involving an ethnically diverse cohort. Asia Pac J Clin Nutr. 1994;3(1):19–31.

    CAS  PubMed  Google Scholar 

  5. Lum A, Le Marchand L. A simple mouthwash method for obtaining genomic DNA in molecular epidemiological studies. Cancer Epidemiol Biomark Prev. 1998;7(8):719–24.

    CAS  Google Scholar 

  6. Miller G. Immortalization of human lymphocytes by Epstein-Barr virus. Yale J Biol Med. 1982;55(3–4):305–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Lindor NM, Burgart LJ, Leontovich O, Goldberg RM, Cunningham JM, Sargent DJ, et al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol. 2002;20(4):1043–8. https://doi.org/10.1200/jco.20.4.1043.

    Article  CAS  PubMed  Google Scholar 

  8. Buchanan DD, Sweet K, Drini M, Jenkins MA, Win AK, English DR, et al. Risk factors for colorectal cancer in patients with multiple serrated polyps: a cross-sectional case series from genetics clinics. PLoS One. 2010;5(7):e11636. https://doi.org/10.1371/journal.pone.0011636

    Article  PubMed  PubMed Central  Google Scholar 

  9. Buchanan DD, Win AK, Walsh MD, Walters RJ, Clendenning M, Nagler BN, et al. Family history of colorectal cancer in BRAF p.V600E mutated colorectal cancer cases. Cancer Epidemiol Biomark Prev. 2013;22(5):917–26. https://doi.org/10.1158/1055-9965.epi-12-1211.

    Article  CAS  Google Scholar 

  10. Weisenberger DJ, Levine AJ, Long TI, Buchanan DD, Walters R, Clendenning M, et al. Association of the colorectal CpG island methylator phenotype with molecular features, risk factors, and family history. Cancer Epidemiol Biomark Prev. 2015;24(3):512–9. https://doi.org/10.1158/1055-9965.EPI-14-1161.

    Article  CAS  Google Scholar 

  11. Levine AJ, Win AK, Buchanan DD, Jenkins MA, Baron JA, Young JP, et al. Cancer risks for the relatives of colorectal cancer cases with a methylated MLH1 promoter region: data from the Colorectal Cancer Family Registry. Cancer Prev Res. 2012;5(2):328–35. https://doi.org/10.1158/1940-6207.CAPR-11-0419.

    Article  PubMed  Google Scholar 

  12. Lindor NM, Rabe K, Petersen GM, Haile R, Casey G, Baron J, et al. Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. JAMA. 2005;293(16):1979–85. https://doi.org/10.1001/jama.293.16.1979.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. The 1000 Genomes Project Consortium. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491(7422):56–65. https://doi.org/10.1038/nature11632.

    Article  CAS  PubMed Central  Google Scholar 

  14. Dowty JG, Win AK, Buchanan DD, Lindor NM, Macrae FA, Clendenning M, et al. Cancer risks for MLH1 and MSH2 mutation carriers. Hum Mutat. 2013;34(3):490–7. https://doi.org/10.1002/humu.22262.

    Article  CAS  PubMed  Google Scholar 

  15. Baglietto L, Lindor NM, Dowty JG, White DM, Wagner A, Gomez Garcia EB, et al. Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst. 2010;102(3):193–201. https://doi.org/10.1093/jnci/djp473.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Senter L, Clendenning M, Sotamaa K, Hampel H, Green J, Potter JD, et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology. 2008;135(2):419–28. https://doi.org/10.1053/j.gastro.2008.04.026.

    Article  CAS  PubMed  Google Scholar 

  17. Win AK, Young JP, Lindor NM, Tucker KM, Ahnen DJ, Young GP, et al. Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study. J Clin Oncol. 2012;30(9):958–64. https://doi.org/10.1200/jco.2011.39.5590.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Guindalini RS, Win AK, Gulden C, Lindor NM, Newcomb PA, Haile RW, et al. Mutation spectrum and risk of colorectal cancer in African American families with Lynch syndrome. Gastroenterology. 2015;149(6):1446–53. https://doi.org/10.1053/j.gastro.2015.07.052.

    Article  CAS  PubMed  Google Scholar 

  19. Parry S, Win AK, Parry B, Macrae FA, Gurrin LC, Church JM, et al. Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery. Gut. 2011;60(7):950–7. https://doi.org/10.1136/gut.2010.228056.

    Article  PubMed  Google Scholar 

  20. Win AK, Parry S, Parry B, Kalady MF, Macrae FA, Ahnen DJ, et al. Risk of metachronous colon cancer following surgery for rectal cancer in mismatch repair gene mutation carriers. Ann Surg Oncol. 2013;20(6):1829–36. https://doi.org/10.1245/s10434-012-2858-5.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Win AK, Lindor NM, Young JP, Macrae FA, Young GP, Williamson E, et al. Risks of primary extracolonic cancers following colorectal cancer in Lynch syndrome. J Natl Cancer Inst. 2012;104(18):1363–72. https://doi.org/10.1093/jnci/djs351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Obermair A, Youlden DR, Young JP, Lindor NM, Baron JA, Newcomb P, et al. Risk of endometrial cancer for women diagnosed with HNPCC-related colorectal carcinoma. Int J Cancer. 2010;127(11):2678–84. https://doi.org/10.1002/ijc.25501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Win AK, Lindor NM, Winship I, Tucker KM, Buchanan DD, Young JP, et al. Risks of colorectal and other cancers after endometrial cancer for women with Lynch syndrome. J Natl Cancer Inst. 2013;105(4):274–9. https://doi.org/10.1093/jnci/djs525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Heath JA, Reece JC, Buchanan DD, Casey G, Durno CA, Gallinger S, et al. Childhood cancers in families with and without Lynch syndrome. Fam Cancer. 2015;14(4):545–51. https://doi.org/10.1007/s10689-015-9810-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Win AK, Dowty JG, Antill YC, English DR, Baron JA, Young JP, et al. Body mass index in early adulthood and endometrial cancer risk for mismatch repair gene mutation carriers. Obstet Gynecol. 2011;117(4):899–905. https://doi.org/10.1097/AOG.0b013e3182110ea3.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Win AK, Dowty JG, English DR, Campbell PT, Young JP, Winship I, et al. Body mass index in early adulthood and colorectal cancer risk for carriers and non-carriers of germline mutations in DNA mismatch repair genes. Br J Cancer. 2011;105(1):162–9. https://doi.org/10.1038/bjc.2011.172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Pande M, Lynch PM, Hopper JL, Jenkins MA, Gallinger S, Haile RW, et al. Smoking and colorectal cancer in Lynch syndrome: results from the Colon Cancer Family Registry and the University of Texas M.D. Anderson Cancer Center. Clin Cancer Res. 2010;16(4):1331–9. https://doi.org/10.1158/1078-0432.ccr-09-1877.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dashti SG, Buchanan DD, Jayasekara H, Ait Ouakrim D, Clendenning M, Rosty C, et al. Alcohol consumption and the risk of colorectal cancer for mismatch repair gene mutation carriers. Cancer Epidemiol Biomark Prev. 2017;26(3):366–75. https://doi.org/10.1158/1055-9965.epi-16-0496.

    Article  Google Scholar 

  29. Ait Ouakrim D, Dashti SG, Chau R, Buchanan DD, Clendenning M, Rosty C, et al. Aspirin, ibuprofen, and the risk of colorectal cancer in Lynch syndrome. J Natl Cancer Inst. 2015;107(9). https://doi.org/10.1093/jnci/djv170.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Chau R, Dashti SG, Ait Ouakrim D, Buchanan DD, Clendenning M, Rosty C, et al. Multivitamin, calcium and folic acid supplements and the risk of colorectal cancer in Lynch syndrome. Int J Epidemiol. 2016;45(3):940–53. https://doi.org/10.1093/ije/dyw036.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Dashti SG, Chau R, Ouakrim DA, Buchanan DD, Clendenning M, Young JP, et al. Female hormonal factors and the risk of endometrial cancer in Lynch syndrome. JAMA. 2015;314(1):61–71. https://doi.org/10.1001/jama.2015.6789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Win AK, Clendenning M, Crawford W, Rosty C, Preston SG, Southey MC, et al. Genetic variants within the hTERT gene and the risk of colorectal cancer in Lynch syndrome. Genes Cancer. 2015;6(11–12):445–51. https://doi.org/10.18632/genesandcancer.85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Win AK, Reece JC, Buchanan DD, Clendenning M, Young JP, Cleary SP, et al. Risk of colorectal cancer for people with a mutation in both a MUTYH and a DNA mismatch repair gene. Fam Cancer. 2015;14(4):575–83. https://doi.org/10.1007/s10689-015-9824-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Win AK, Hopper JL, Buchanan DD, Young JP, Tenesa A, Dowty JG, et al. Are the common genetic variants associated with colorectal cancer risk for DNA mismatch repair gene mutation carriers? Eur J Cancer. 2013;49(7):1578–87. https://doi.org/10.1016/j.ejca.2013.01.029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Stupart D, Win AK, Jenkins M, Winship IM, Goldberg P, Ramesar R. Fertility and apparent genetic anticipation in Lynch syndrome. Fam Cancer. 2014;13(3):369–74. https://doi.org/10.1007/s10689-014-9714-7.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Stupart D, Win AK, Winship IM, Jenkins M. Fertility after young-onset colorectal cancer: a study of subjects with Lynch syndrome. Colorectal Dis. 2015;17(9):787–93. https://doi.org/10.1111/codi.12940.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Shiovitz S, Copeland WK, Passarelli MN, Burnett-Hartman AN, Grady WM, Potter JD, et al. Characterisation of familial colorectal cancer Type X, Lynch syndrome, and non-familial colorectal cancer. Br J Cancer. 2014;111(3):598–602. https://doi.org/10.1038/bjc.2014.309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Walsh MD, Cummings MC, Pearson SA, Clendenning M, Walters RJ, Nagler B, et al. Lynch syndrome-associated breast cancers do not overexpress chromosome 11-encoded mucins. Modern Pathol. 2013;26(7):944–54. https://doi.org/10.1038/modpathol.2012.232.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Antill YC, Dowty JG, Win AK, Thompson T, Walsh MD, Cummings MC, et al. Lynch syndrome and cervical cancer. Int J Cancer. 2015;137(11):2757–61. https://doi.org/10.1002/ijc.29641.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Rosty C, Walsh MD, Lindor NM, Thibodeau SN, Mundt E, Gallinger S, et al. High prevalence of mismatch repair deficiency in prostate cancers diagnosed in mismatch repair gene mutation carriers from the Colon Cancer Family Registry. Fam Cancer. 2014;13(4):573–82. https://doi.org/10.1007/s10689-014-9744-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Toon CW, Walsh MD, Chou A, Capper D, Clarkson A, Sioson L, et al. BRAFV600E immunohistochemistry facilitates universal screening of colorectal cancers for Lynch syndrome. Am J Surg Pathol. 2013;37(10):1592–602. https://doi.org/10.1097/PAS.0b013e31828f233d.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Newton K, Jorgensen NM, Wallace AJ, Buchanan DD, Lalloo F, RF MM, et al. Tumour MLH1 promoter region methylation testing is an effective prescreen for Lynch Syndrome (HNPCC). J Med Genet. 2014;51(12):789–96. https://doi.org/10.1136/jmedgenet-2014-102552.

    Article  CAS  PubMed  Google Scholar 

  43. Tomsic J, Senter L, Liyanarachchi S, Clendenning M, Vaughn CP, Jenkins MA, et al. Recurrent and founder mutations in the PMS2 gene. Clin Genet. 2013;83(3):238–43. https://doi.org/10.1111/j.1399-0004.2012.01898.x.

    Article  CAS  PubMed  Google Scholar 

  44. Win AK, Jenkins MA, Buchanan DD, Clendenning M, Young JP, Giles GG, et al. Determining the frequency of de novo germline mutations in DNA mismatch repair genes. J Med Genet. 2011;48(8):530–4. https://doi.org/10.1136/jmedgenet-2011-100082.

    Article  CAS  PubMed  Google Scholar 

  45. Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, et al. Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. Nat Genet. 2014;46(2):107–15. https://doi.org/10.1038/ng.2854.

    Article  CAS  PubMed  Google Scholar 

  46. Thompson BA, Greenblatt MS, Vallee MP, Herkert JC, Tessereau C, Young EL, et al. Calibration of multiple in silico tools for predicting pathogenicity of mismatch repair gene missense substitutions. Hum Mutat. 2013;34(1):255–65. https://doi.org/10.1002/humu.22214.

    Article  CAS  PubMed  Google Scholar 

  47. Thompson BA, Goldgar DE, Paterson C, Clendenning M, Walters R, Arnold S, et al. A multifactorial likelihood model for MMR gene variant classification incorporating probabilities based on sequence bioinformatics and tumor characteristics: a report from the Colon Cancer Family Registry. Hum Mutat. 2013;34(1):200–9. https://doi.org/10.1002/humu.22213.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Win AK, Jenkins MA, Dowty JG, Antoniou AC, Lee A, Giles GG, et al. Prevalence and penetrance of major genes and polygenes for colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2017;26(3):404–12. https://doi.org/10.1158/1055-9965.epi-16-0693.

    Article  CAS  PubMed  Google Scholar 

  49. Win AK, Dowty JG, Cleary SP, Kim H, Buchanan DD, Young JP, et al. Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer. Gastroenterology. 2014;146(5):1208–11. e1-5. https://doi.org/10.1053/j.gastro.2014.01.022.

    Article  CAS  PubMed  Google Scholar 

  50. Jenkins MA, Croitoru ME, Monga N, Cleary SP, Cotterchio M, Hopper JL, et al. Risk of colorectal cancer in monoallelic and biallelic carriers of MYH mutations: a population-based case-family study. Cancer Epidemiol Biomark Prev. 2006;15(2):312–4. https://doi.org/10.1158/1055-9965.epi-05-0793.

    Article  CAS  Google Scholar 

  51. Win AK, Reece JC, Dowty JG, Buchanan DD, Clendenning M, Rosty C, et al. Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH. Int J Cancer. 2016;139(7):1557–63. https://doi.org/10.1002/ijc.30197.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Win AK, Cleary SP, Dowty JG, Baron JA, Young JP, Buchanan DD, et al. Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer. Int J Cancer. 2011;129(9):2256–62. https://doi.org/10.1002/ijc.25870.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Phipps AI, Lindor NM, Jenkins MA, Baron JA, Win AK, Gallinger S, et al. Colon and rectal cancer survival by tumor location and microsatellite instability: the Colon Cancer Family Registry. Dis Colon Rectum. 2013;56(8):937–44. https://doi.org/10.1097/DCR.0b013e31828f9a57.

    Article  Google Scholar 

  54. Lynch PM. Colorectal cancer survival by location and microsatellite status: data from the Colon Cancer Family Registries and their implications. Dis Colon Rectum. 2013;56(8):935–6. https://doi.org/10.1097/DCR.0b013e31828f9954.

    Article  Google Scholar 

  55. Phipps AI, Buchanan DD, Makar KW, Burnett-Hartman AN, Coghill AE, Passarelli MN, et al. BRAF mutation status and survival after colorectal cancer diagnosis according to patient and tumor characteristics. Cancer Epidemiol Biomark Prev. 2012;21(10):1792–8. https://doi.org/10.1158/1055-9965.epi-12-0674.

    Article  CAS  Google Scholar 

  56. Levine AJ, Phipps AI, Baron JA, Buchanan DD, Ahnen DJ, Cohen SA, et al. Clinicopathologic risk factor distributions for MLH1 promoter region methylation in CIMP-positive tumors. Cancer Epidemiol Biomark Prev. 2016;25(1):68–75. https://doi.org/10.1158/1055-9965.epi-15-0935.

    Article  Google Scholar 

  57. Phipps AI, Limburg PJ, Baron JA, Burnett-Hartman AN, Weisenberger DJ, Laird PW, et al. Association between molecular subtypes of colorectal cancer and patient survival. Gastroenterology. 2015;148(1):77–87. e2. https://doi.org/10.1053/j.gastro.2014.09.038.

    Article  CAS  PubMed  Google Scholar 

  58. Phipps AI, Buchanan DD, Makar KW, Win AK, Baron JA, Lindor NM, et al. KRAS-mutation status in relation to colorectal cancer survival: the joint impact of correlated tumour markers. Br J Cancer. 2013;108(8):1757–64. https://doi.org/10.1038/bjc.2013.118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Phipps AI, Ahnen DJ, Cheng I, Newcomb PA, Win AK, Burnett T. PIK3CA somatic mutation status in relation to patient and tumor factors in racial/ethnic minorities with colorectal cancer. Cancer Epidemiol Biomark Prev. 2015;24(7):1046–51. https://doi.org/10.1158/1055-9965.epi-15-0204.

    Article  CAS  Google Scholar 

  60. Loo LW, Tiirikainen M, Cheng I, Lum-Jones A, Seifried A, Church JM, et al. Integrated analysis of genome-wide copy number alterations and gene expression in microsatellite stable, CpG island methylator phenotype-negative colon cancer. Genes Chromosomes Cancer. 2013;52(5):450–66. https://doi.org/10.1002/gcc.22043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Passarelli MN, Coghill AE, Hutter CM, Zheng Y, Makar KW, Potter JD, et al. Common colorectal cancer risk variants in SMAD7 are associated with survival among prediagnostic nonsteroidal anti-inflammatory drug users: a population-based study of postmenopausal women. Genes Chromosomes Cancer. 2011;50(11):875–86. https://doi.org/10.1002/gcc.20913.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Slattery ML, Curtin K, Poole EM, Duggan DJ, Samowitz WS, Peters U, et al. Genetic variation in C-reactive protein in relation to colon and rectal cancer risk and survival. Int J Cancer. 2011;128(11):2726–34. https://doi.org/10.1002/ijc.25721.

    Article  CAS  PubMed  Google Scholar 

  63. Coghill AE, Newcomb PA, Poole EM, Hutter CM, Makar KW, Duggan D, et al. Genetic variation in inflammatory pathways is related to colorectal cancer survival. Clin Cancer Res. 2011;17(22):7139–47. https://doi.org/10.1158/1078-0432.ccr-11-1134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Passarelli MN, Newcomb PA, Makar KW, Burnett-Hartman AN, Phipps AI, David SP, et al. No association between germline variation in catechol-O-methyltransferase and colorectal cancer survival in postmenopausal women. Menopause. 2014;21(4):415–20. https://doi.org/10.1097/GME.0b013e31829e498d.

  65. Passarelli MN, Phipps AI, Potter JD, Makar KW, Coghill AE, Wernli KJ, et al. Common single-nucleotide polymorphisms in the estrogen receptor beta promoter are associated with colorectal cancer survival in postmenopausal women. Cancer Res. 2013;73(2):767–75. https://doi.org/10.1158/0008-5472.can-12-2484.

    Article  CAS  PubMed  Google Scholar 

  66. Phipps AI, Ahnen DJ, Campbell PT, Win AK, Jenkins MA, Lindor NM, et al. Family history of colorectal cancer is not associated with colorectal cancer survival regardless of microsatellite instability status. Cancer Epidemiol Biomark Prev. 2014;23(8):1700–4. https://doi.org/10.1158/1055-9965.epi-14-0533.

    Article  Google Scholar 

  67. Adams SV, Ahnen DJ, Baron JA, Campbell PT, Gallinger S, Grady WM, et al. Survival after inflammatory bowel disease-associated colorectal cancer in the Colon Cancer Family Registry. World J Gastroenterol. 2013;19(21):3241–8. https://doi.org/10.3748/wjg.v19.i21.3241.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Campbell PT, Newton CC, Newcomb PA, Phipps AI, Ahnen DJ, Baron JA, et al. Association between body mass index and mortality for colorectal cancer survivors: overall and by tumor molecular phenotype. Cancer Epidemiol Biomark Prev. 2015;24(8):1229–38. https://doi.org/10.1158/1055-9965.epi-15-0094.

    Article  CAS  Google Scholar 

  69. Phipps AI, Baron J, Newcomb PA. Prediagnostic smoking history, alcohol consumption, and colorectal cancer survival: the Seattle Colon Cancer Family Registry. Cancer. 2011;117(21):4948–57. https://doi.org/10.1002/cncr.26114.

    Article  PubMed  Google Scholar 

  70. Phipps AI, Robinson JR, Campbell PT, Win AK, Figueiredo JC, Lindor NM, et al. Prediagnostic alcohol consumption and colorectal cancer survival: the Colon Cancer Family Registry. Cancer. 2016. https://doi.org/10.1002/cncr.30446.

  71. Coghill AE, Newcomb PA, Campbell PT, Burnett-Hartman AN, Adams SV, Poole EM, et al. Prediagnostic non-steroidal anti-inflammatory drug use and survival after diagnosis of colorectal cancer. Gut. 2011;60(4):491–8. https://doi.org/10.1136/gut.2010.221143.

    Article  PubMed  Google Scholar 

  72. Coghill AE, Newcomb PA, Chia VM, Zheng Y, Wernli KJ, Passarelli MN, et al. Pre-diagnostic NSAID use but not hormone therapy is associated with improved colorectal cancer survival in women. Br J Cancer. 2011;104(5):763–8. https://doi.org/10.1038/sj.bjc.6606041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Hardikar S, Newcomb PA, Campbell PT, Win AK, Lindor NM, Buchanan DD, et al. Prediagnostic physical activity and colorectal cancer survival: overall and stratified by tumor characteristics. Cancer Epidemiol Biomark Prev. 2015;24(7):1130–7. https://doi.org/10.1158/1055-9965.epi-15-0039.

    Article  Google Scholar 

  74. Jayasekara H, Reece JC, Buchanan DD, Rosty C, Dashti SG, Ait Ouakrim D, et al. Risk factors for metachronous colorectal cancer following a primary colorectal cancer: a prospective cohort study. Int J Cancer. 2016;139(5):1081–90. https://doi.org/10.1002/ijc.30153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Cleary SP, Cotterchio M, Shi E, Gallinger S, Harper P. Cigarette smoking, genetic variants in carcinogen-metabolizing enzymes, and colorectal cancer risk. Am J Epidemiol. 2010;172(9):1000–14. https://doi.org/10.1093/aje/kwq245.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Campbell PT, Jacobs ET, Ulrich CM, Figueiredo JC, Poynter JN, JR ML, et al. Case–control study of overweight, obesity, and colorectal cancer risk, overall and by tumor microsatellite instability status. J Natl Cancer Inst. 2010;102(6):391–400. https://doi.org/10.1093/jnci/djq011.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Wernli KJ, Wang Y, Zheng Y, Potter JD, Newcomb PA. The relationship between gravidity and parity and colorectal cancer risk. J Women's Health. 2009;18(7):995–1001. https://doi.org/10.1089/jwh.2008.1068.

    Article  Google Scholar 

  78. Boardman LA, Morlan BW, Rabe KG, Petersen GM, Lindor NM, Nigon SK, et al. Colorectal cancer risks in relatives of young-onset cases: is risk the same across all first-degree relatives? Clin Gastroenterol Hepatol. 2007;5(10):1195–8. https://doi.org/10.1016/j.cgh.2007.06.001.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Lindor NM, Rabe KG, Petersen GM, Chen H, Bapat B, Hopper J, et al. Parent of origin effects on age at colorectal cancer diagnosis. Int J Cancer. 2010;127(2):361–6. https://doi.org/10.1002/ijc.25037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Gong J, Hutter CM, Newcomb PA, Ulrich CM, Bien SA, Campbell PT, et al. Genome-wide interaction analyses between genetic variants and alcohol consumption and smoking for risk of colorectal cancer. PLoS Genet. 2016;12(10):e1006296. https://doi.org/10.1371/journal.pgen.1006296.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Makar KW, Poole EM, Resler AJ, Seufert B, Curtin K, Kleinstein SE, et al. COX-1 (PTGS1) and COX-2 (PTGS2) polymorphisms, NSAID interactions, and risk of colon and rectal cancers in two independent populations. Cancer Causes Control. 2013;24(12):2059–75. https://doi.org/10.1007/s10552-013-0282-1.

    Article  Google Scholar 

  82. Nan H, Hutter CM, Lin Y, Jacobs EJ, Ulrich CM, White E, et al. Association of aspirin and NSAID use with risk of colorectal cancer according to genetic variants. JAMA. 2015;313(11):1133–42. https://doi.org/10.1001/jama.2015.1815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Resler AJ, Makar KW, Heath L, Whitton J, Potter JD, Poole EM, et al. Genetic variation in prostaglandin synthesis and related pathways, NSAID use and colorectal cancer risk in the Colon Cancer Family Registry. Carcinogenesis. 2014;35(9):2121–6. https://doi.org/10.1093/carcin/bgu119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Scherer D, Koepl LM, Poole EM, Balavarca Y, Xiao L, Baron JA, et al. Genetic variation in UGT genes modify the associations of NSAIDs with risk of colorectal cancer: Colon Cancer Family Registry. Genes Chromosomes Cancer. 2014;53(7):568–78. https://doi.org/10.1002/gcc.22167.

    Article  CAS  PubMed  Google Scholar 

  85. Seufert BL, Poole EM, Whitton J, Xiao L, Makar KW, Campbell PT, et al. IkappaBKbeta and NFkappaB1, NSAID use and risk of colorectal cancer in the Colon Cancer Family Registry. Carcinogenesis. 2013;34(1):79–85. https://doi.org/10.1093/carcin/bgs296.

  86. Campbell PT, Newcomb P, Gallinger S, Cotterchio M, McLaughlin JR. Exogenous hormones and colorectal cancer risk in Canada: associations stratified by clinically defined familial risk of cancer. Cancer Causes Control. 2007;18(7):723–33. https://doi.org/10.1007/s10552-007-9015-7.

    Article  Google Scholar 

  87. Campbell PT, Cotterchio M, Klar N, JR ML, Gallinger S. Colorectal cancer risk among post-menopausal hormone users in a population-based familial case-control study. Ann Epidemiol. 2003;13(8):562. https://doi.org/10.1016/S1047-2797(03)00144-3.

    Article  Google Scholar 

  88. Garcia-Albeniz X, Rudolph A, Hutter C, White E, Lin Y, Rosse SA, et al. CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk. Br J Cancer. 2016;114(2):221–9. https://doi.org/10.1038/bjc.2015.443.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Figueiredo J, Levine A, Lee W, Conti D, Poynter J, Campbell P, et al. Genes involved with folate uptake and distribution and their association with colorectal cancer risk. Cancer Causes Control. 2010;21(4):597–608. https://doi.org/10.1007/s10552-009-9489-6.

    Article  PubMed  Google Scholar 

  90. Levine AJ, Figueiredo JC, Lee W, Poynter JN, Conti D, Duggan DJ, et al. Genetic variability in the MTHFR gene and Colorectal cancer risk using the Colorectal Cancer Family Registry. Cancer Epidemiol Biomark Prev. 2010;19(1):89–100. https://doi.org/10.1158/1055-9965.epi-09-0727.

    Article  CAS  Google Scholar 

  91. Levine AJ, Figueiredo JC, Lee W, Conti DV, Kennedy K, Duggan DJ, et al. A candidate gene study of folate-associated one carbon metabolism genes and colorectal cancer risk. Cancer Epidemiol Biomark Prev. 2010;19(7):1812–21. https://doi.org/10.1158/1055-9965.EPI-10-0151.

    Article  CAS  Google Scholar 

  92. Kim HS, Newcomb PA, Ulrich CM, Keener CL, Bigler J, Farin FM, et al. Vitamin D receptor polymorphism and the risk of colorectal adenomas. Cancer Epidemiol Biomark Prev. 2001;10(8):869–74.

    CAS  Google Scholar 

  93. Poynter JN, Jacobs ET, Figueiredo JC, Lee WH, Conti DV, Campbell PT, et al. Genetic variation in the vitamin D receptor (VDR) and the vitamin D-binding protein (GC) and risk for colorectal cancer: results from the Colon Cancer Family Registry. Cancer Epidemiol Biomark Prev. 2010;19(2):525–36. https://doi.org/10.1158/1055-9965.EPI-09-0662.

    Article  CAS  Google Scholar 

  94. Sun Z, Wang PP, Roebothan B, Cotterchio M, Green R, Buehler S et al. Calcium and vitamin D and risk of colorectal cancer: results from a large population-based case-control study in Newfoundland and Labrador and Ontario. Can J Public Health. 2011;102(5):382-9.

    Google Scholar 

  95. Hiraki LT, Qu C, Hutter CM, Baron JA, Berndt SI, Bezieau S, et al. Genetic predictors of circulating 25-hydroxyvitamin d and risk of colorectal cancer. Cancer Epidemiol Biomark Prev. 2013;22(11):2037–46. https://doi.org/10.1158/1055-9965.epi-13-0209.

  96. Du M, Zhang X, Hoffmeister M, Schoen RE, Baron JA, Berndt SI, et al. No evidence of gene-calcium interactions from genome-wide analysis of colorectal cancer risk. Cancer Epidemiol Biomark Prev. 2014;23(12):2971–6. https://doi.org/10.1158/1055-9965.epi-14-0893.

  97. Joshi AD, Corral R, Siegmund KD, Haile RW, Le Marchand L, Martinez ME, et al. Red meat and poultry intake, polymorphisms in the nucleotide excision repair and mismatch repair pathways and colorectal cancer risk. Carcinogenesis. 2009;30(3):472–9. https://doi.org/10.1093/carcin/bgn260.

    Article  CAS  PubMed  Google Scholar 

  98. Cotterchio M, Boucher BA, Manno M, Gallinger S, Okey AB, Harper PA. Red meat intake, doneness, polymorphisms in genes that encode carcinogen-metabolizing enzymes, and colorectal cancer risk. Cancer Epidemiol Biomark Prev. 2008;17(11):3098–107. https://doi.org/10.1158/1055-9965.epi-08-0341.

    Article  CAS  Google Scholar 

  99. Chia VM, Newcomb PA, Lampe JW, White E, Mandelson MT, McTiernan A, et al. Leptin concentrations, leptin receptor polymorphisms, and colorectal adenoma risk. Cancer Epidemiol Biomark Prev. 2007;16(12):2697–703. https://doi.org/10.1158/1055-9965.EPI-07-0467.

    Article  CAS  Google Scholar 

  100. Cotterchio M, Boucher BA, Manno M, Gallinger S, Okey A, Harper P. Dietary phytoestrogen intake is associated with reduced colorectal cancer risk. J Nutr. 2006;136(12):3046–53.

    Article  CAS  PubMed  Google Scholar 

  101. Sun Z, Zhu Y, Wang PP, Roebothan B, Zhao J, Dicks E, et al. Reported intake of selected micronutrients and risk of colorectal cancer: results from a large population-based case-control study in Newfoundland, Labrador and Ontario, Canada. Anticancer Res. 2012;32(2):687–96.

    CAS  PubMed  Google Scholar 

  102. Thrift AP, Gong J, Peters U, Chang-Claude J, Rudolph A, Slattery ML, et al. Mendelian randomization study of height and risk of colorectal cancer. Int J Epidemiol. 2015;44(2):662–72. https://doi.org/10.1093/ije/dyv082.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Thrift AP, Gong J, Peters U, Chang-Claude J, Rudolph A, Slattery ML, et al. Mendelian randomization study of body mass index and colorectal cancer risk. Cancer Epidemiol Biomark Prev. 2015;24(7):1024–31. https://doi.org/10.1158/1055-9965.epi-14-1309.

  104. Jarvis D, Mitchell JS, Law PJ, Palin K, Tuupanen S, Gylfe A, et al. Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer. Br J Cancer. 2016;115(2):266–72. https://doi.org/10.1038/bjc.2016.188.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Houlston RS, Webb E, Broderick P, Pittman AM, Di Bernardo MC, Lubbe S, et al. Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer. Nat Genet. 2008;40(12):1426–35. https://doi.org/10.1038/ng.262.

    Article  CAS  PubMed  Google Scholar 

  106. Tenesa A, Farrington SM, Prendergast JG, Porteous ME, Walker M, Haq N, et al. Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21. Nat Genet. 2008;40(5):631–7. https://doi.org/10.1038/ng.133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Poynter JN, Figueiredo JC, Conti DV, Kennedy K, Gallinger S, Siegmund KD, et al. Variants on 9p24 and 8q24 are associated with risk of colorectal cancer: results from the Colon Cancer Family Registry. Cancer Res. 2007;67(23):11128–32. https://doi.org/10.1158/0008-5472.can-07-3239.

    Article  CAS  PubMed  Google Scholar 

  108. Schumacher FR, Schmit SL, Jiao S, Edlund CK, Wang H, Zhang B, et al. Genome-wide association study of colorectal cancer identifies six new susceptibility loci. Nat Commun. 2015;6:7138. https://doi.org/10.1038/ncomms8138.

    Article  PubMed  Google Scholar 

  109. Al-Tassan NA, Whiffin N, Hosking FJ, Palles C, Farrington SM, Dobbins SE, et al. A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer. Sci Rep. 2015;5:10442. https://doi.org/10.1038/srep10442.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Cheng I, Kocarnik JM, Dumitrescu L, Lindor NM, Chang-Claude J, Avery CL, et al. Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia. Gut. 2014;63(5):800–7. https://doi.org/10.1136/gutjnl-2013-305189.

    Article  CAS  PubMed  Google Scholar 

  111. Cheng TH, Thompson D, Painter J, O’Mara T, Gorman M, Martin L, et al. Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1. Sci Rep. 2015;5:17369. https://doi.org/10.1038/srep17369.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Lemire M, Qu C, Loo LW, Zaidi SH, Wang H, Berndt SI, et al. A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1. Hum Genet. 2015;134(11–12):1249–62. https://doi.org/10.1007/s00439-015-1598-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Whiffin N, Hosking FJ, Farrington SM, Palles C, Dobbins SE, Zgaga L, et al. Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis. Hum Mol Genet. 2014;23(17):4729–37. https://doi.org/10.1093/hmg/ddu177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Zeng C, Matsuda K, Jia WH, Chang J, Kweon SS, Xiang YB, et al. Identification of susceptibility loci and genes for colorectal cancer risk. Gastroenterology. 2016;150(7):1633–45. https://doi.org/10.1053/j.gastro.2016.02.076.

    Article  CAS  PubMed  Google Scholar 

  115. Jia WH, Zhang B, Matsuo K, Shin A, Xiang YB, Jee SH, et al. Genome-wide association analyses in east Asians identify new susceptibility loci for colorectal cancer. Nat Genet. 2013;45(2):191–6. https://doi.org/10.1038/ng.2505.

    Article  CAS  PubMed  Google Scholar 

  116. Wang H, Haiman CA, Burnett T, Fortini BK, Kolonel LN, Henderson BE, et al. Fine-mapping of genome-wide association study-identified risk loci for colorectal cancer in African Americans. Hum Mol Genet. 2013;22(24):5048–55. https://doi.org/10.1093/hmg/ddt337.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Wang H, Burnett T, Kono S, Haiman CA, Iwasaki M, Wilkens LR, et al. Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A. Nat Commun. 2014;5:4613. https://doi.org/10.1038/ncomms5613.

    Article  CAS  PubMed  Google Scholar 

  118. Dunlop MG, Tenesa A, Farrington SM, Ballereau S, Brewster DH, Koessler T, et al. Cumulative impact of common genetic variants and other risk factors on colorectal cancer risk in 42,103 individuals. Gut. 2013;62(6):871–81. https://doi.org/10.1136/gutjnl-2011-300537.

    Article  CAS  PubMed  Google Scholar 

  119. Roberts A, Nancarrow D, Clendenning M, Buchanan DD, Jenkins MA, Duggan D, et al. Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome). Fam Cancer. 2011;10(2):245–54. https://doi.org/10.1007/s10689-010-9408-8.

    Article  PubMed Central  Google Scholar 

  120. Zogopoulos G, Jorgensen C, Bacani J, Montpetit A, Lepage P, Ferretti V, et al. Germline EPHB2 receptor variants in familial colorectal cancer. PLoS One. 2008;3(8):e2885. https://doi.org/10.1371/journal.pone.0002885.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Young J, Jass JR. The case for a genetic predisposition to serrated neoplasia in the colorectum: hypothesis and review of the literature. Cancer Epidemiol Biomark Prev. 2006;15(10):1778–84. https://doi.org/10.1158/1055-9965.epi-06-0164.

    Article  CAS  Google Scholar 

  122. Young J, Jenkins M, Parry S, Young B, Nancarrow D, English D, et al. Serrated pathway colorectal cancer in the population: genetic consideration. Gut. 2007;56(10):1453–9. https://doi.org/10.1136/gut.2007.126870.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Yeoman A, Young J, Arnold J, Jass J, Parry S. Hyperplastic polyposis in the New Zealand population: a condition associated with increased colorectal cancer risk and European ancestry. N Z Med J. 2007;120(1266):U2827.

    PubMed  Google Scholar 

  124. Jiang X, Castelao JE, Vandenberg D, Carracedo A, Redondo CM, Conti DV, et al. Genetic variations in SMAD7 are associated with colorectal cancer risk in the Colon Cancer Family Registry. PLoS One. 2013;8(4):e60464. https://doi.org/10.1371/journal.pone.0060464.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Chang CM, Chia VM, Gunter MJ, Zanetti KA, Ryan BM, Goodman JE, et al. Innate immunity gene polymorphisms and the risk of colorectal neoplasia. Carcinogenesis. 2013;34(11):2512–20. https://doi.org/10.1093/carcin/bgt228.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Wang H, Taverna D, Stram DO, Fortini BK, Cheng I, Wilkens LR, et al. Genetic variation in the inflammation and innate immunity pathways and colorectal cancer risk. Cancer Epidemiol Biomark Prev. 2013;22(11):2094–101. https://doi.org/10.1158/1055-9965.epi-13-0694.

    Article  CAS  Google Scholar 

  127. Abbenhardt C, Poole EM, Kulmacz RJ, Xiao L, Curtin K, Galbraith RL, et al. Phospholipase A2G1B polymorphisms and risk of colorectal neoplasia. Int J Mol Epidemiol Genet. 2013;4(3):140–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Akbari MR, Anderson LN, Buchanan DD, Clendenning M, Jenkins MA, Win AK, et al. Germline HOXB13 p.Gly84Glu mutation and risk of colorectal cancer. Cancer Epidemiol. 2013;37(4):424–7. https://doi.org/10.1016/j.canep.2013.03.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Yurgelun MB, Masciari S, Joshi VA, Mercado RC, Lindor NM, Gallinger S, et al. Germline TP53mutations in patients with early-onset colorectal cancer in the Colon Cancer Family Registry. JAMA Oncol. 2015;1(2):214–21. https://doi.org/10.1001/jamaoncol.2015.0197.

    Article  PubMed  Google Scholar 

  130. Bapat B, Lindor NM, Baron J, Siegmund K, Li L, Zheng Y, et al. The association of tumor microsatellite instability phenotype with family history of colorectal cancer. Cancer Epidemiol Biomark Prev. 2009;18(3):967–75. https://doi.org/10.1158/1055-9965.EPI-08-0878.

    Article  CAS  Google Scholar 

  131. English DR, Young JP, Simpson JA, Jenkins MA, Southey MC, Walsh MD, et al. Ethnicity and risk for colorectal cancers showing somatic BRAF V600E mutation or CpG island methylator phenotype. Cancer Epidemiol Biomark Prev. 2008;17(7):1774–80. https://doi.org/10.1158/1055-9965.EPI-08-0091.

    Article  CAS  Google Scholar 

  132. Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006;38(7):787–93. https://doi.org/10.1038/ng1834.

    Article  CAS  PubMed  Google Scholar 

  133. Kambara T, Simms LA, VLJ W, Spring KJ, CVA W, Walsh MD, et al. BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut. 2004;53(8):1137–44. https://doi.org/10.1136/gut.2003.037671.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Hitchins M, Williams R, Cheong K, Halani N, Lin VAP, Packham D, et al. MLH1 Germline Epimutations as a factor in hereditary nonpolyposis colorectal cancer. Gastroenterology. 2005;129(5):1392–9. https://doi.org/10.1053/j.gastro.2005.09.003.

    Article  CAS  PubMed  Google Scholar 

  135. Coolbaugh-Murphy MI, Xu J, Ramagli LS, Brown BW, Siciliano MJ. Microsatellite instability (MSI) increases with age in normal somatic cells. Mech Ageing Dev. 2005;126(10):1051–9. https://doi.org/10.1016/j.mad.2005.06.005.

    Article  CAS  PubMed  Google Scholar 

  136. Kakar S, Burgart LJ, Thibodeau SN, Rabe KG, Petersen GM, Goldberg RM, et al. Frequency of loss of hMLH1 expression in colorectal carcinoma increases with advancing age. Cancer. 2003;97(6):1421–7. https://doi.org/10.1002/cncr.11206.

    Article  CAS  PubMed  Google Scholar 

  137. Savio AJ, Daftary D, Dicks E, Buchanan DD, Parfrey PS, Young JP, et al. Promoter methylation of ITF2, but not APC, is associated with microsatellite instability in two populations of colorectal cancer patients. BMC Cancer. 2016;16:113. https://doi.org/10.1186/s12885-016-2149-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Walters RJ, Williamson EJ, English DR, Young JP, Rosty C, Clendenning M, et al. Association between hypermethylation of DNA repetitive elements in white blood cell DNA and early-onset colorectal cancer. Epigenetics. 2013;8(7):748–55. https://doi.org/10.4161/epi.25178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Win AK, Jenkins MA, Dowty JG, Antoniou AC, Lee A, Giles GG, et al. Prevalence and penetrance of major genes and polygenes for colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2016. https://doi.org/10.1158/1055-9965.EPI-16-0693.

  140. Kastrinos F, Ojha RP, Leenen C, Alvero C, Mercado RC, Balmana J, et al. Comparison of prediction models for Lynch syndrome among individuals with colorectal cancer. J Natl Cancer Inst. 2016;108(2). https://doi.org/10.1093/jnci/djv308.

  141. Kastrinos F, Steyerberg EW, Balmana J, Mercado R, Gallinger S, Haile R, et al. Comparison of the clinical prediction model PREMM(1,2,6) and molecular testing for the systematic identification of Lynch syndrome in colorectal cancer. Gut. 2013;62(2):272–9. https://doi.org/10.1136/gutjnl-2011-301265.

    Article  PubMed  Google Scholar 

  142. Kastrinos F, Steyerberg EW, Mercado R, Balmana J, Holter S, Gallinger S, et al. The PREMM(1,2,6) model predicts risk of MLH1, MSH2, and MSH6 germline mutations based on cancer history. Gastroenterology. 2011;140(1):73–81. https://doi.org/10.1053/j.gastro.2010.08.021.

    Article  CAS  PubMed  Google Scholar 

  143. Casey G, Lindor NM, Papadopoulos N, Thibodeau SN, Moskow J, Steelman S, et al. Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer. JAMA. 2005;293(7):799–809. https://doi.org/10.1001/jama.293.7.799.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Cleary SP, Kim H, Croitoru ME, Redston M, Knight JA, Gallinger S, et al. Missense polymorphisms in the adenomatous polyposis coli gene and colorectal cancer risk. Dis Colon Rectum. 2008;51(10):1467–73; discussion 1473-74. https://doi.org/10.1007/s10350-008-9356-7.

    Article  Google Scholar 

  145. Hahnloser D, Petersen GM, Rabe K, Snow K, Lindor NM, Boardman L, et al. The APC E1317Q variant in adenomatous polyps and colorectal cancers. Cancer Epidemiol Biomark Prev. 2003;12(10):1023–8.

    Google Scholar 

  146. Jaskowski L, Young J, Jackson L, Arnold S, Barker MA, Walsh MD, et al. Stability of BAT26 in Lynch syndrome colorectal tumours. Eur J Hum Genet. 2007;15(2):139–41; author reply 41-2. https://doi.org/10.1038/sj.ejhg.5201740.

    Article  PubMed  Google Scholar 

  147. Jenkins MA, Hayashi S, O'Shea AM, Burgart LJ, Smyrk TC, Shimizu D, et al. Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study. Gastroenterology. 2007;133(1):48–56. https://doi.org/10.1053/j.gastro.2007.04.044.

    Article  CAS  PubMed  Google Scholar 

  148. Zogopoulos G, Ha KC, Naqib F, Moore S, Kim H, Montpetit A, et al. Germ-line DNA copy number variation frequencies in a large North American population. Hum Genet. 2007;122(3–4):345–53. https://doi.org/10.1007/s00439-007-0404-5.

    Article  CAS  PubMed  Google Scholar 

  149. Clendenning M, Macrae FA, Walsh MD, Walters RJ, Thibodeau SN, Gunawardena SR, et al. Absence of PMS2 mutations in Colon-CFR participants whose colorectal cancers demonstrate unexplained loss of MLH1 expression. Clin Genet. 2013;83(6):591–3. https://doi.org/10.1111/cge.12011.

    Article  PubMed  PubMed Central  Google Scholar 

  150. Clendenning M, Walsh MD, Gelpi JB, Thibodeau SN, Lindor N, Potter JD, et al. Detection of large scale 3′ deletions in the PMS2 gene amongst Colon-CFR participants: have we been missing anything? Fam Cancer. 2013;12(3):563–6. https://doi.org/10.1007/s10689-012-9597-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Cunningham JM, Johnson RA, Litzelman K, Skinner HG, Seo S, Engelman CD, et al. Telomere length varies by DNA extraction method: implications for epidemiologic research. Cancer Epidemiol Biomark Prev. 2013;22(11):2047–54. https://doi.org/10.1158/1055-9965.epi-13-0409.

  152. Boardman LA, Litzelman K, Seo S, Johnson RA, Vanderboom RJ, Kimmel GW, et al. The association of telomere length with colorectal cancer differs by the age of cancer onset. Clinical and Translat Gastroenterol. 2014;5:e52. https://doi.org/10.1038/ctg.2014.3.

    Article  CAS  Google Scholar 

  153. Kuroiwa-Trzmielina J, Wang F, Rapkins RW, Ward RL, Buchanan DD, Win AK, et al. SNP rs16906252C>T is an expression and methylation quantitative trait locus associated with an increased risk of developing MGMT-methylated colorectal cancer. Clin Cancer Res. 2016;22(24):6266–77. https://doi.org/10.1158/1078-0432.ccr-15-2765.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Uddin M, Thiruvahindrapuram B, Walker S, Wang Z, Hu P, Lamoureux S, et al. A high-resolution copy-number variation resource for clinical and population genetics. Genet Med. 2015;17(9):747–52. https://doi.org/10.1038/gim.2014.178.

    Article  PubMed  PubMed Central  Google Scholar 

  155. Win AK, Buchanan DD, Rosty C, RJ MI, Dowty JG, Dite GS, et al. Role of tumour molecular and pathology features to estimate colorectal cancer risk for first-degree relatives. Gut. 2015;64(1):101–10. https://doi.org/10.1136/gutjnl-2013-306567.

    Article  PubMed  Google Scholar 

  156. Kim JS, Coyte PC, Cotterchio M, Keogh LA, Flander LB, Gaff C, et al. The impact of receiving predictive genetic information about Lynch syndrome on individual colonoscopy and smoking behaviors. Cancer Epidemiol Biomark Prev. 2016;25(11):1524–33. https://doi.org/10.1158/1055-9965.epi-16-0346.

    Article  Google Scholar 

  157. Esplen MJ, Wong J, Aronson M, Butler K, Rothenmund H, Semotiuk K, et al. Long-term psychosocial and behavioral adjustment in individuals receiving genetic test results in Lynch syndrome. Clin Genet. 2015;87(6):525–32. https://doi.org/10.1111/cge.12509.

    Article  CAS  PubMed  Google Scholar 

  158. Graves KD, Sinicrope PS, Esplen MJ, Peterson SK, Patten CA, Lowery J, et al. Communication of genetic test results to family and health-care providers following disclosure of research results. Genet Med. 2014;16(4):294–301. https://doi.org/10.1038/gim.2013.137.

    Article  PubMed  Google Scholar 

  159. Patel SG, Ahnen DJ, Kinney AY, Horick N, Finkelstein DM, Hill DA, et al. Knowledge and uptake of genetic counseling and colonoscopic screening among individuals at increased risk for Lynch syndrome and their endoscopists from the Family Health Promotion Project. Am J Gastroenterol. 2016;111(2):285–93. https://doi.org/10.1038/ajg.2015.397.

    Article  PubMed  PubMed Central  Google Scholar 

  160. Flander L, Speirs-Bridge A, Rutstein A, Niven H, Win AK, Ait Ouakrim D, et al. Perceived versus predicted risks of colorectal cancer and self-reported colonoscopies by members of mismatch repair gene mutation-carrying families who have declined genetic testing. J Genet Couns. 2014;23(1):79–88. https://doi.org/10.1007/s10897-013-9614-2.

    Article  PubMed  Google Scholar 

  161. Steel EJ, Trainer AH, Heriot AG, Lynch C, Parry S, Win AK, et al. The experience of extended bowel resection in individuals with a high metachronous colorectal cancer risk: a qualitative study. Oncol Nurs Forum. 2016;43(4):444–52. https://doi.org/10.1188/16.onf.444-452.

    Article  PubMed  PubMed Central  Google Scholar 

  162. Adams SV, Ceballos R, Newcomb PA. Quality of life and mortality of long-term colorectal cancer survivors in the Seattle Colorectal Cancer Family Registry. PLoS One. 2016;11(6):e0156534. https://doi.org/10.1371/journal.pone.0156534.

    Article  PubMed  PubMed Central  Google Scholar 

  163. Howell LA, Brockman TA, Sinicrope PS, Patten CA, Decker PA, Ehlers SL, et al. Receptivity and preferences in cancer risk reduction lifestyle programs: a survey of colorectal cancer family members. J Behav Health. 2013;2(4):279–90. https://doi.org/10.5455/jbh.20130921013627.

    Article  PubMed  PubMed Central  Google Scholar 

  164. Lowery JT, Horick N, Kinney AY, Finkelstein DM, Garrett K, Haile RW, et al. A randomized trial to increase colonoscopy screening in members of high-risk families in the Colorectal Cancer Family Registry and Cancer Genetics Network. Cancer Epidemiol Biomark Prev. 2014;23(4):601–10. https://doi.org/10.1158/1055-9965.epi-13-1085.

    Article  Google Scholar 

  165. Bharati R, Jenkins MA, Lindor NM, Le Marchand L, Gallinger S, Haile RW, et al. Does risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair gene depend on family history of endometrial cancer or colorectal cancer? Gynecol Oncol. 2014;133(2):287–92. https://doi.org/10.1016/j.ygyno.2014.03.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Ahsan H, Halpern J, Kibriya MG, Pierce BL, Tong L, Gamazon E, et al. A genome-wide association study of early-onset breast cancer identifies PFKM as a novel breast cancer gene and supports a common genetic spectrum for breast cancer at any age. Cancer Epidemiol Biomark Prev. 2014;23(4):658–69. https://doi.org/10.1158/1055-9965.epi-13-0340.

  167. Anderson LN, Cotterchio M, Knight JA, Borgida A, Gallinger S, Cleary SP. Genetic variants in vitamin D pathway genes and risk of pancreas cancer; results from a population-based case-control study in Ontario, Canada. PLoS One. 2013;8(6):e66768. https://doi.org/10.1371/journal.pone.0066768.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Bosetti C, Lucenteforte E, Bracci PM, Negri E, Neale RE, Risch HA, et al. Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the international pancreatic cancer case-control consortium (PanC4). Ann Oncol. 2013;24(11):2903–10. https://doi.org/10.1093/annonc/mdt336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Jang JH, Cotterchio M, Borgida A, Liu G, Gallinger S, Cleary SP. Interaction of polymorphisms in mitotic regulator genes with cigarette smoking and pancreatic cancer risk. Mol Carcinog. 2013;52(Suppl 1):E103–9. https://doi.org/10.1002/mc.22037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Olson SH, Hsu M, Satagopan JM, Maisonneuve P, Silverman DT, Lucenteforte E, et al. Allergies and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer case-control consortium. Am J Epidemiol. 2013;178(5):691–700. https://doi.org/10.1093/aje/kwt052.

    Article  PubMed  PubMed Central  Google Scholar 

  171. Bosetti C, Rosato V, Li D, Silverman D, Petersen GM, Bracci PM, et al. Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the international pancreatic cancer case-control consortium. Ann Oncol. 2014;25(10):2065–72. https://doi.org/10.1093/annonc/mdu276.

  172. Vasen HF, Mecklin JP, Khan PM, Lynch HT. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum. 1991;34(5):424–5.

    Article  CAS  PubMed  Google Scholar 

  173. Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC. Gastroenterology. 1999;116(6):1453–6.

    Article  CAS  PubMed  Google Scholar 

  174. Jarvinen HJ, Aarnio M, Mustonen H, Aktan-Collan K, Aaltonen LA, Peltomaki P et al. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 2000;118(5):829–834.

    Article  PubMed  Google Scholar 

  175. Burn J, Gerdes AM, Macrae F, Mecklin JP, Moeslein G, Olschwang S, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet. 2011;378(9809):2081–7. https://doi.org/10.1016/S0140-6736(11)61049-0.

    Article  PubMed  PubMed Central  Google Scholar 

  176. Hopper JL. Disease-specific prospective family study cohorts enriched for familial risk. Epidemiol Perspect Innov. 2011;8(1):2. https://doi.org/10.1186/1742-5573-8-2.

    Article  Google Scholar 

  177. Cicek MS, Cunningham JM, Fridley BL, Serie DJ, Bamlet WR, Diergaarde B et al. Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22. PLoS One. 2012;7(5):e38175. https://doi.org/10.1371/journal.pone.0038175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Neklason DW, Kerber RA, Nilson DB, Anton-Culver H, Schwartz AG, Griffin CA et al. Common familial colorectal cancer linked to chromosome 7q31: a genome-wide analysis. Cancer Res. 2008;68(21):8993–7. https://doi.org/10.1158/0008-5472.can-08-1376.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Gray-McGuire C, Guda K, Adrianto I, Lin CP, Natale L, Potter JD et al. Confirmation of linkage to and localization of familial colon cancer risk haplotype on chromosome 9q22. Cancer Res. 2010;70(13):5409–18. https://doi.org/10.1158/0008-5472.can-10-0188.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. DeRycke MS, Gunawardena SR, Middha S, Asmann YW, Schaid DJ, McDonnell SK et al. Identification of novel variants in colorectal cancer families by high-throughput exome sequencing. Cancer Epidemiol Biomarkers Prev. 2013;22(7):1239-51. https://doi.org/10.1158/1055-9965.epi-12-1226.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grant UM1 CA167551 from the National Cancer Institute and through cooperative agreements with the following CCFRC sites: Australasian Colorectal Cancer Family Registry (U01 CA074778 and U01/U24 CA097735), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01/U24 CA074800), Ontario Familial Colorectal Cancer Registry (U01/U24 CA074783), Seattle Colorectal Cancer Family Registry (U01/U24 CA074794), University of Hawaii Colorectal Cancer Family Registry (U01/U24 CA074806) and USC Consortium Colorectal Cancer Family Registry (U01/U24 CA074799). The targeted minority recruitment was supported by grant R01 CA104132. The genome-wide association studies (GWAS) were supported by grants U01 CA 122839, R01 CA143237 and U19 CA148107. The CIMP and KRAS mutation testing was supported by R01 CA118699.

Additional support for case ascertainment was provided from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute to Fred Hutchinson Cancer Research Center (Control Nos. N01-CN-67009 and N01-PC-35142 and Contract No. HHSN2612013000121), the Hawaii Department of Health (Control Nos. N01-PC-67001 and N01-PC-35137 and Contract No. HHSN26120100037C) and the California Department of Public Health (contracts HHSN261201000035C awarded to the University of Southern California and HHSN261201000140C awarded to the Cancer Prevention Institute of California), by the following US state cancer registries, AZ, CO, MN, NC, and NH, and by the Victorian Cancer Registry, Australia and the Ontario Cancer Registry, Canada. AKW is an Australian National Health and Medical Research Council (NHMRC) Early Career Fellow. MAJ is an NHMRC Senior Research Fellow.

Author information

Authors and Affiliations

  1. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia

    Mark A. Jenkins & Aung K. Win

  2. University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia

    Mark A. Jenkins & Aung K. Win

  3. Genetic Medicine and Familial Cancer Centre, The Royal Melbourne Hospital, Parkville, VIC, Australia

    Aung K. Win

  4. Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ, USA

    Noralane M. Lindor

Authors
  1. Mark A. Jenkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aung K. Win
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Noralane M. Lindor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark A. Jenkins .

Editor information

Editors and Affiliations

  1. Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL and CIBERONC, Hospitalet de Llobregat, Barcelona, Spain

    Laura Valle

  2. University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, California, USA

    Stephen B. Gruber

  3. Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL and CIBERONC, Hospitalet de Llobregat, Barcelona, Spain

    Gabriel Capellá

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Jenkins, M.A., Win, A.K., Lindor, N.M. (2018). The Colon Cancer Family Registry Cohort. In: Valle, L., Gruber, S., Capellá, G. (eds) Hereditary Colorectal Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-74259-5_27

Download citation

Publish with us

Policies and ethics

Search

Navigation