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Colorectal Tumor Risk Prediction in the PLCO Trial

Principal Investigator
Name
ULRIKE PETERS
Institution
FRED HUTCHINSON CANCER RESEARCH CENTER
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2014-0244
Title
Colorectal Tumor Risk Prediction in the PLCO Trial
Summary
Despite slight declines in colorectal cancer (CRC) incidence, it remains the second leading cause of cancer death. Paradoxically, it is among the most preventable and treatable of neoplastic diseases when detected early via screening. In the U.S., endoscopic screening, particularly colonoscopy, is the most commonly used strategy by the population at risk; however, it is costly, invasive, and carries risks, leading to overall low utilization in the population. Current screening recommendations are based only on age, family history of CRC, and previous screening results, whereas incidence of CRC varies substantially in the population and most cases occur in those without a positive family history. Therefore, the goal of this proposal is to develop, calibrate, and validate a comprehensive risk-prediction model incorporating genome-wide genetic data, as well as lifestyle and environmental risk factors, such as obesity, medication, smoking, and diet, which can provide a more accurate risk stratification for those at risk. The model would permit identification and prioritization of individuals at higher CRC risk for targeted screening and intervention, while reducing emphasis for those at low risk. In Aim 1 we will develop a comprehensive CRC risk-prediction model within the large existing Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which includes over 14,000 cases and 15,300 controls with existing detailed genetic data from genome-wide genotyping arrays and whole genome sequencing, as well as harmonized clinical and epidemiologic variables (U01-CA137088, U01-CA164930). In Aim 2 we will undertake independent validation of the model in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. In PLCO, in addition to using the rich clinical and epidemiologic data, we will genotype and impute genetic variants across the genome in all 1,522 incident CRC cases, all 2,604 advanced adenoma cases with DNA, and 3,000 randomly selected controls. Including advanced adenoma will uniquely allow us to evaluate risk prediction for an important precursor lesion of CRC. Risk-prediction model for left- and right-sided CRC will be compared to account for flexible-sigmoidoscopy screening. In Aim 3 we will compare within PLCO our comprehensive model with current screening guidelines and published risk-prediction models to estimate the improvement of our model in comparison with existing guidelines and other prediction models. Our proposal leverages the extensive efforts to discover genetic and environmental risk factors for CRC, and offers the potential for pragmatic application to the population. Genetic testing is already part of routine care and it is expected that genetic data wil increasingly become part of an individual's medical record. Utilizing genetic and non-genetic risk-factor information in clinical and preventive settings is a critical step towards developing more personalized medicine based on risk stratification. Our model can be used for tailored screening and prevention strategies that are more cost-efficient and may increase adherence.
Aims

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Collaborators

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Related Publications
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    BMC Med. 2020 Dec 17; Volume 18 (Issue 1): Pages 396 PUBMED
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  • Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses.
    Seyed Khoei N, Jenab M, Murphy N, Banbury BL, Carreras-Torres R, Viallon V, Kühn T, Bueno-de-Mesquita B, Aleksandrova K, Cross AJ, Weiderpass E, Stepien M, Bulmer A, Tjønneland A, Boutron-Ruault MC, Severi G, Carbonnel F, Katzke V, Boeing H, Bergmann MM, ...show more Trichopoulou A, Karakatsani A, Martimianaki G, Palli D, Tagliabue G, Panico S, Tumino R, Sacerdote C, Skeie G, Merino S, Bonet C, Rodríguez-Barranco M, Gil L, Chirlaque MD, Ardanaz E, Myte R, Hultdin J, Perez-Cornago A, Aune D, Tsilidis KK, Albanes D, Baron JA, Berndt SI, Bézieau S, Brenner H, Campbell PT, Casey G, Chan AT, Chang-Claude J, Chanock SJ, Cotterchio M, Gallinger S, Gruber SB, Haile RW, Hampe J, Hoffmeister M, Hopper JL, Hsu L, Huyghe JR, Jenkins MA, Joshi AD, Kampman E, Larsson SC, Le Marchand L, Li CI, Li L, Lindblom A, Lindor NM, Martín V, Moreno V, Newcomb PA, Offit K, Ogino S, Parfrey PS, Pharoah PDP, Rennert G, Sakoda LC, Schafmayer C, Schmit SL, Schoen RE, Slattery ML, Thibodeau SN, Ulrich CM, van Duijnhoven FJB, Weigl K, Weinstein SJ, White E, Wolk A, Woods MO, Wu AH, Zhang X, Ferrari P, Anton G, Peters A, Peters U, Gunter MJ, Wagner KH, Freisling H
    BMC Med. 2020 Sep 3; Volume 18 (Issue 1): Pages 229 PUBMED
  • Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.
    Thomas M, Sakoda LC, Hoffmeister M, Rosenthal EA, Lee JK, van Duijnhoven FJB, Platz EA, Wu AH, Dampier CH, de la Chapelle A, Wolk A, Joshi AD, Burnett-Hartman A, Gsur A, Lindblom A, Castells A, Win AK, Namjou B, Van Guelpen B, Tangen CM, ...show more He Q, Li CI, Schafmayer C, Joshu CE, Ulrich CM, Bishop DT, Buchanan DD, Schaid D, Drew DA, Muller DC, Duggan D, Crosslin DR, Albanes D, Giovannucci EL, Larson E, Qu F, Mentch F, Giles GG, Hakonarson H, Hampel H, Stanaway IB, Figueiredo JC, Huyghe JR, Minnier J, Chang-Claude J, Hampe J, Harley JB, Visvanathan K, Curtis KR, Offit K, Li L, Le Marchand L, Vodickova L, Gunter MJ, Jenkins MA, Slattery ML, Lemire M, Woods MO, Song M, Murphy N, Lindor NM, Dikilitas O, Pharoah PDP, Campbell PT, Newcomb PA, Milne RL, MacInnis RJ, Castellví-Bel S, Ogino S, Berndt SI, Bézieau S, Thibodeau SN, Gallinger SJ, Zaidi SH, Harrison TA, Keku TO, Hudson TJ, Vymetalkova V, Moreno V, Martín V, Arndt V, Wei WQ, Chung W, Su YR, Hayes RB, White E, Vodicka P, Casey G, Gruber SB, Schoen RE, Chan AT, Potter JD, Brenner H, Jarvik GP, Corley DA, Peters U, Hsu L
    Am J Hum Genet. 2020 Sep 3; Volume 107 (Issue 3): Pages 432-444 PUBMED
  • Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.
    Zhang YD, Hurson AN, Zhang H, Choudhury PP, Easton DF, Milne RL, Simard J, Hall P, Michailidou K, Dennis J, Schmidt MK, Chang-Claude J, Gharahkhani P, Whiteman D, Campbell PT, Hoffmeister M, Jenkins M, Peters U, Hsu L, Gruber SB, ...show more Casey G, Schmit SL, O'Mara TA, Spurdle AB, Thompson DJ, Tomlinson I, De Vivo I, Landi MT, Law MH, Iles MM, Demenais F, Kumar R, MacGregor S, Bishop DT, Ward SV, Bondy ML, Houlston R, Wiencke JK, Melin B, Barnholtz-Sloan J, Kinnersley B, Wrensch MR, Amos CI, Hung RJ, Brennan P, McKay J, Caporaso NE, Berndt SI, Birmann BM, Camp NJ, Kraft P, Rothman N, Slager SL, Berchuck A, Pharoah PDP, Sellers TA, Gayther SA, Pearce CL, Goode EL, Schildkraut JM, Moysich KB, Amundadottir LT, Jacobs EJ, Klein AP, Petersen GM, Risch HA, Stolzenberg-Solomon RZ, Wolpin BM, Li D, Eeles RA, Haiman CA, Kote-Jarai Z, Schumacher FR, Al Olama AA, Purdue MP, Scelo G, Dalgaard MD, Greene MH, Grotmol T, Kanetsky PA, McGlynn KA, Nathanson KL, Turnbull C, Wiklund F, Breast Cancer Association Consortium (BCAC), Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON), Colon Cancer Family Registry (CCFR), Transdisciplinary Studies of Genetic Variation in Colorectal Cancer (CORECT), Endometrial Cancer Association Consortium (ECAC), Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Melanoma Genetics Consortium (GenoMEL), Glioma International Case-Control Study (GICC), International Lung Cancer Consortium (ILCCO), Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium, International Consortium of Investigators Working on Non-Hodgkin’s Lymphoma Epidemiologic Studies (InterLymph), Ovarian Cancer Association Consortium (OCAC), Oral Cancer GWAS, Pancreatic Cancer Case-Control Consortium (PanC4), Pancreatic Cancer Cohort Consortium (PanScan), Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL), Renal Cancer GWAS, Testicular Cancer Consortium (TECAC), Chanock SJ, Chatterjee N, Garcia-Closas M
    Nat Commun. 2020 Jul 3; Volume 11 (Issue 1): Pages 3353 PUBMED
  • Mendelian Randomization of Circulating Polyunsaturated Fatty Acids and Colorectal Cancer Risk.
    Khankari NK, Banbury BL, Borges MC, Haycock P, Albanes D, Arndt V, Berndt SI, Bézieau S, Brenner H, Campbell PT, Casey G, Chan AT, Chang-Claude J, Conti DV, Cotterchio M, English DR, Figueiredo JC, Giles GG, Giovannucci EL, Gunter MJ, ...show more Hampe J, Hoffmeister M, Hopper JL, Jenkins MA, Joshi AD, Marchand LL, Lemire M, Li CI, Li L, Lindblom A, Martín V, Moreno V, Newcomb PA, Offit K, Pharoah PDP, Rennert G, Sakoda LC, Schafmayer C, Schmit SL, Slattery ML, Song M, Thibodeau SN, Ulrich CM, Weinstein SJ, White E, Win AK, Wolk A, Woods MO, Wu AH, Cai Q, Denny JC, Edwards TL, Murff HJ, Gruber SB, Peters U, Zheng W
    Cancer Epidemiol. Biomarkers Prev. 2020 Feb 12 PUBMED
  • Meta-analysis of 16 studies of the association of alcohol with colorectal cancer.
    McNabb S, Harrison TA, Albanes D, Berndt SI, Brenner H, Caan BJ, Campbell PT, Cao Y, Chang-Claude J, Chan A, Chen Z, English DR, Giles GG, Giovannucci EL, Goodman PJ, Hayes RB, Hoffmeister M, Jacobs EJ, Joshi AD, Larsson SC, ...show more Le Marchand L, Li L, Lin Y, Männistö S, Milne RL, Nan H, Newton CC, Ogino S, Parfrey PS, Petersen PS, Potter JD, Schoen RE, Slattery ML, Su YR, Tangen CM, Tucker TC, Weinstein SJ, White E, Wolk A, Woods MO, Phipps AI, Peters U
    Int. J. Cancer. 2020 Feb 1; Volume 146 (Issue 3): Pages 861-873 PUBMED
  • Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis.
    Papadimitriou N, Dimou N, Tsilidis KK, Banbury B, Martin RM, Lewis SJ, Kazmi N, Robinson TM, Albanes D, Aleksandrova K, Berndt SI, Timothy Bishop D, Brenner H, Buchanan DD, Bueno-de-Mesquita B, Campbell PT, Castellví-Bel S, Chan AT, Chang-Claude J, Ellingjord-Dale M, ...show more Figueiredo JC, Gallinger SJ, Giles GG, Giovannucci E, Gruber SB, Gsur A, Hampe J, Hampel H, Harlid S, Harrison TA, Hoffmeister M, Hopper JL, Hsu L, María Huerta J, Huyghe JR, Jenkins MA, Keku TO, Kühn T, La Vecchia C, Le Marchand L, Li CI, Li L, Lindblom A, Lindor NM, Lynch B, Markowitz SD, Masala G, May AM, Milne R, Monninkhof E, Moreno L, Moreno V, Newcomb PA, Offit K, Perduca V, Pharoah PDP, Platz EA, Potter JD, Rennert G, Riboli E, Sánchez MJ, Schmit SL, Schoen RE, Severi G, Sieri S, Slattery ML, Song M, Tangen CM, Thibodeau SN, Travis RC, Trichopoulou A, Ulrich CM, van Duijnhoven FJB, Van Guelpen B, Vodicka P, White E, Wolk A, Woods MO, Wu AH, Peters U, Gunter MJ, Murphy N
    Nat Commun. 2020 Jan 30; Volume 11 (Issue 1): Pages 597 PUBMED
  • DNA repair and cancer in colon and rectum: Novel players in genetic susceptibility.
    Pardini B, Corrado A, Paolicchi E, Cugliari G, Berndt SI, Bezieau S, Bien SA, Brenner H, Caan BJ, Campbell PT, Casey G, Chan AT, Chang-Claude J, Cotterchio M, Gala M, Gallinger SJ, Haile RW, Harrison TA, Hayes RB, Hoffmeister M, ...show more Hopper JL, Hsu L, Huyghe J, Jenkins MA, Le Marchand L, Lin Y, Lindor NM, Nan H, Newcomb PA, Ogino S, Potter JD, Schoen RE, Slattery ML, White E, Vodickova L, Vymetalkova V, Vodicka P, Gemignani F, Peters U, Naccarati A, Landi S
    Int. J. Cancer. 2020 Jan 15; Volume 146 (Issue 2): Pages 363-372 PUBMED
  • Combined effect of modifiable and non-modifiable risk factors for colorectal cancer risk in a pooled analysis of 11 population-based studies.
    Wang X, O'Connell K, Jeon J, Song M, Hunter D, Hoffmeister M, Lin Y, Berndt S, Brenner H, Chan AT, Chang-Claude J, Gong J, Gunter MJ, Harrison TA, Hayes RB, Joshi A, Newcomb P, Schoen R, Slattery ML, Vargas A, ...show more Potter JD, Le Marchand L, Giovannucci E, White E, Hsu L, Peters U, Du M
    BMJ Open Gastroenterol. 2019; Volume 6 (Issue 1): Pages e000339 PUBMED
  • Discovery of common and rare genetic risk variants for colorectal cancer.
    Huyghe JR, Bien SA, Harrison TA, Kang HM, Chen S, Schmit SL, Conti DV, Qu C, Jeon J, Edlund CK, Greenside P, Wainberg M, Schumacher FR, Smith JD, Levine DM, Nelson SC, Sinnott-Armstrong NA, Albanes D, Alonso MH, Anderson K, ...show more Arnau-Collell C, Arndt V, Bamia C, Banbury BL, Baron JA, Berndt SI, Bézieau S, Bishop DT, Boehm J, Boeing H, Brenner H, Brezina S, Buch S, Buchanan DD, Burnett-Hartman A, Butterbach K, Caan BJ, Campbell PT, Carlson CS, Castellví-Bel S, Chan AT, Chang-Claude J, Chanock SJ, Chirlaque MD, Cho SH, Connolly CM, Cross AJ, Cuk K, Curtis KR, de la Chapelle A, Doheny KF, Duggan D, Easton DF, Elias SG, Elliott F, English DR, Feskens EJM, Figueiredo JC, Fischer R, FitzGerald LM, Forman D, Gala M, Gallinger S, Gauderman WJ, Giles GG, Gillanders E, Gong J, Goodman PJ, Grady WM, Grove JS, Gsur A, Gunter MJ, Haile RW, Hampe J, Hampel H, Harlid S, Hayes RB, Hofer P, Hoffmeister M, Hopper JL, Hsu WL, Huang WY, Hudson TJ, Hunter DJ, Ibañez-Sanz G, Idos GE, Ingersoll R, Jackson RD, Jacobs EJ, Jenkins MA, Joshi AD, Joshu CE, Keku TO, Key TJ, Kim HR, Kobayashi E, Kolonel LN, Kooperberg C, Kühn T, Küry S, Kweon SS, Larsson SC, Laurie CA, Le Marchand L, Leal SM, Lee SC, Lejbkowicz F, Lemire M, Li CI, Li L, Lieb W, Lin Y, Lindblom A, Lindor NM, Ling H, Louie TL, Männistö S, Markowitz SD, Martín V, Masala G, McNeil CE, Melas M, Milne RL, Moreno L, Murphy N, Myte R, Naccarati A, Newcomb PA, Offit K, Ogino S, Onland-Moret NC, Pardini B, Parfrey PS, Pearlman R, Perduca V, Pharoah PDP, Pinchev M, Platz EA, Prentice RL, Pugh E, Raskin L, Rennert G, Rennert HS, Riboli E, Rodríguez-Barranco M, Romm J, Sakoda LC, Schafmayer C, Schoen RE, Seminara D, Shah M, Shelford T, Shin MH, Shulman K, Sieri S, Slattery ML, Southey MC, Stadler ZK, Stegmaier C, Su YR, Tangen CM, Thibodeau SN, Thomas DC, Thomas SS, Toland AE, Trichopoulou A, Ulrich CM, Van Den Berg DJ, van Duijnhoven FJB, Van Guelpen B, van Kranen H, Vijai J, Visvanathan K, Vodicka P, Vodickova L, Vymetalkova V, Weigl K, Weinstein SJ, White E, Win AK, Wolf CR, Wolk A, Woods MO, Wu AH, Zaidi SH, Zanke BW, Zhang Q, Zheng W, Scacheri PC, Potter JD, Bassik MC, Kundaje A, Casey G, Moreno V, Abecasis GR, Nickerson DA, Gruber SB, Hsu L, Peters U
    Nat. Genet. 2019; Volume 51 (Issue 1): Pages 76-87 PUBMED
  • Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses.
    Murphy N, Carreras-Torres R, Song M, Chan AT, Martin RM, Papadimitriou N, Dimou N, Tsilidis KK, Banbury B, Bradbury KE, Besevic J, Rinaldi S, Riboli E, Cross AJ, Travis RC, Agnoli C, Albanes D, Berndt SI, Bézieau S, Bishop DT, ...show more Brenner H, Buchanan DD, Onland-Moret NC, Burnett-Hartman A, Campbell PT, Casey G, Castellví-Bel S, Chang-Claude J, Chirlaque MD, de la Chapelle A, English D, Figueiredo JC, Gallinger SJ, Giles GG, Gruber SB, Gsur A, Hampe J, Hampel H, Harrison TA, Hoffmeister M, Hsu L, Huang WY, Huyghe JR, Jenkins MA, Keku TO, Kühn T, Kweon SS, Le Marchand L, Li CI, Li L, Lindblom A, Martín V, Milne RL, Moreno V, Newcomb PA, Offit K, Ogino S, Ose J, Perduca V, Phipps AI, Platz EA, Potter JD, Qu C, Rennert G, Sakoda LC, Schafmayer C, Schoen RE, Slattery ML, Tangen CM, Ulrich CM, van Duijnhoven FJB, Van Guelpen B, Visvanathan K, Vodicka P, Vodickova L, Vymetalkova V, Wang H, White E, Wolk A, Woods MO, Wu AH, Zheng W, Peters U, Gunter MJ
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  • Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.
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  • Mendelian randomization analysis of C-reactive protein on colorectal cancer risk.
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  • Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer.
    Bien SA, Su YR, Conti DV, Harrison TA, Qu C, Guo X, Lu Y, Albanes D, Auer PL, Banbury BL, Berndt SI, Bézieau S, Brenner H, Buchanan DD, Caan BJ, Campbell PT, Carlson CS, Chan AT, Chang-Claude J, Chen S, ...show more Connolly CM, Easton DF, Feskens EJM, Gallinger S, Giles GG, Gunter MJ, Hampe J, Huyghe JR, Hoffmeister M, Hudson TJ, Jacobs EJ, Jenkins MA, Kampman E, Kang HM, Kühn T, Küry S, Lejbkowicz F, Le Marchand L, Milne RL, Li L, Li CI, Lindblom A, Lindor NM, Martín V, McNeil CE, Melas M, Moreno V, Newcomb PA, Offit K, Pharaoh PDP, Potter JD, Qu C, Riboli E, Rennert G, Sala N, Schafmayer C, Scacheri PC, Schmit SL, Severi G, Slattery ML, Smith JD, Trichopoulou A, Tumino R, Ulrich CM, van Duijnhoven FJB, Van Guelpen B, Weinstein SJ, White E, Wolk A, Woods MO, Wu AH, Abecasis GR, Casey G, Nickerson DA, Gruber SB, Hsu L, Zheng W, Peters U
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