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Principal Investigator
Name
Wen-Yi Huang
Degrees
-
Institution
NCI, DCEG, OEEB
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2007-0220
Initial CDAS Request Approval
Dec 20, 2007
Title
Coordinated Studies on Etiology of Colorectal Tumors: Study Update and Expansion
Summary
Colorectal adenoma is a recognized precursor to colorectal cancer. We are studying risk factors for these conditions in the PLCO Trial. We have published more than 20 reports on colorectal adenoma etiology and have several investigations ongoing, expanding to studies of colorectal cancer. With an expanded number of cases now available and with improvements in laboratory technology, we update here on the approach for current studies of single nucleotide polymorphisms (SNPs) in a priori putative disease pathways (Aim 1) and of SNPs identified from genome-wide association studies (GWAS) of cancer and related phenotypes (Aim 2). We also propose new investigations, using recently acquired pathology samples, to examine risk factor relationships with specific molecular sub-types of disease (Aim 3), and using peripheral blood samples, to examine genome-wide methylation patterns as disease risk factors (Aim 4).The expanded study includes 2000 colorectal adenoma, 900 colorectal cancer cases and a similar number of controls. This large size case series identified in a nonbiased fashion and the availability of detailed risk factor questionnaires and biologic samples make this a uniquely rich resource for the ongoing and proposed investigations. The hypotheses under study expand on our and other's work, focusing on metabolism and cell-signaling pathways, and include promising new research areas of risk associated with SNP variation in new gene regions, by GWAS, in key response element regulatory sites, and with global methylation patterns. With tumor cores for DNA-based studies and tissue microarrays (TMAs) from cores for protein expression, the study also allows for sub-specification of risk by tumor molecular sub-type, e.g., chromosomal, microsatellite, and immunohistochemical (IHC) changes. Study of genome-wide DNA hypomethylation allows us to relate epigenetic events with genomic instability and colorectal tumor risk. We expect that the study will significantly expand knowledge on colon tumor risk factors, with respect to premalignant and malignant disease. The project is being carried out by a team of epidemiologists, statisticians and laboratory scientists, with a productive track record in this field. It will take approximately two years to complete.
Aims

1. Evaluate risk associations for colorectal tumors for high-priority genes and SNPs (Table 1), including (1) a set of ~500 maximally informative tagging SNPs for antioxidant response elements1 and P53 response elements2;3, and (2) tagging SNPs of ~75 selected genes involved in tobacco and dietary-related metabolism, one-carbon metabolism, NSAIDs metabolism and target, Wnt/beta-catenin signaling, and angiogenesis, as a continuation of the approved Study 2006-128 (Colorectal study update and expansion, Hayes et al). 2. Evaluate risks for colorectal tumors in relation to high-priority genetic associations identified in GWAS studies (e.g., 8q24 risk variants, and potentially obesity-related genes) and other studies, as a continuation of the approved Study 2006-299 (GWAS of colorectal tumors, Zanke et al.) for rapid replication of potentially important findings. 3. Evaluate risk associations for colorectal cancer and adenoma, for environmental and genetic factors in relation to tumor sub-type, as determined from pathologic sample trait analysis. Proposed molecular markers are listed in Table 2. 4. Evaluate risks for colorectal tumors in relation to genome-wide (global) DNA hypomethylation status in peripheral blood.

Collaborators

ULRIKE (RIKI) PETERS, PHD, MPH (Fred Hutchinson Cancer Research Center)

Related Publications
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    Bull CJ, Bell JA, Murphy N, Sanderson E, Davey Smith G, Timpson NJ, Banbury BL, Albanes D, Berndt SI, Bézieau S, Bishop DT, Brenner H, Buchanan DD, Burnett-Hartman A, Casey G, Castellví-Bel S, Chan AT, Chang-Claude J, Cross AJ, de la Chapelle A, Figueiredo JC, Gallinger SJ, Gapstur SM, Giles GG, Gruber SB, Gsur A, Hampe J, Hampel H, Harrison TA, Hoffmeister M, Hsu L, Huang WY, Huyghe JR, Jenkins MA, Joshu CE, Keku TO, Kühn T, Kweon SS, Le Marchand L, Li CI, Li L, Lindblom A, Martín V, May AM, Milne RL, Moreno V, Newcomb PA, Offit K, Ogino S, Phipps AI, Platz EA, Potter JD, Qu C, Quirós JR, Rennert G, Riboli E, Sakoda LC, Schafmayer C, Schoen RE, Slattery ML, Tangen CM, Tsilidis KK, Ulrich CM, van Duijnhoven FJB, van Guelpen B, Visvanathan K, Vodicka P, Vodickova L, Wang H, White E, Wolk A, Woods MO, Wu AH, Campbell PT, Zheng W, Peters U, Vincent EE, Gunter MJ
    BMC Med. 2020 Dec 17; Volume 18 (Issue 1): Pages 396 PUBMED
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    Nat Commun. 2020 Jul 20; Volume 11 (Issue 1): Pages 3644 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, 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, Brenner H, Buchanan DD, Onland-Moret NC, Burnett-Hartman A, Campbell PT, Casey G, Castellví-Bel S, Chang-Claude J, Chirlaque MD, 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 FJ, 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
    Gastroenterology. 2019 Dec 26 PUBMED
  • Cumulative Burden of Colorectal Cancer-Associated Genetic Variants is More Strongly Associated With Early-onset vs Late-onset Cancer.
    Archambault AN, Su YR, Jeon J, Thomas M, Lin Y, Conti DV, Win AK, Sakoda LC, Lansdorp-Vogelaar I, Peterse EF, Zauber AG, Duggan D, Holowatyj AN, Huyghe JR, Brenner H, Cotterchio M, Bézieau S, Schmit SL, Edlund CK, Southey MC, MacInnis RJ, Campbell PT, Chang-Claude J, Slattery ML, Chan AT, Joshi AD, Song M, Cao Y, Woods MO, White E, Weinstein SJ, Ulrich CM, Hoffmeister M, Bien SA, Harrison TA, Hampe J, Li CI, Schafmayer C, Offit K, Pharoah PD, Moreno V, Lindblom A, Wolk A, Wu AH, Li L, Gunter MJ, Gsur A, Keku TO, Pearlman R, Bishop DT, Castellví-Bel S, Moreira L, Vodicka P, Kampman E, Giles GG, Albanes D, Baron JA, Berndt SI, Brezina S, Buch S, Buchanan DD, Trichopoulou A, Severi G, Chirlaque MD, Sánchez MJ, Palli D, Kühn T, Murphy N, Cross AJ, Burnett-Hartman AN, Chanock SJ, Chapelle A, Easton DF, Elliott F, English DR, Feskens EJ, FitzGerald LM, Goodman PJ, Hopper JL, Hudson TJ, Hunter DJ, Jacobs EJ, Joshu CE, Küry S, Markowitz SD, Milne RL, Platz EA, Rennert G, Rennert HS, Schumacher FR, Sandler RS, Seminara D, Tangen CM, Thibodeau SN, Toland AE, van Duijnhoven FJ, Visvanathan K, Vodickova L, Potter JD, Männistö S, Weigl K, Figueiredo J, Martín V, Larsson SC, Parfrey PS, Huang WY, Lenz HJ, Castelao JE, Gago-Dominguez M, Muñoz-Garzón V, Mancao C, Haiman CA, Wilkens LR, Siegel E, Barry E, Younghusband B, Van Guelpen B, Harlid S, Zeleniuch-Jacquotte A, Liang PS, Du M, Casey G, Lindor NM, Le Marchand L, Gallinger SJ, Jenkins MA, Newcomb PA, Gruber SB, Schoen RE, Hampel H, Corley DA, Hsu L, Peters U, Hayes RB
    Gastroenterology. 2019 Dec 19 PUBMED
  • Germline variation in NCF4, an innate immunity gene, is associated with an increased risk of colorectal cancer.
    Ryan BM, Zanetti KA, Robles AI, Schetter AJ, Goodman J, Hayes RB, Huang WY, Gunter MJ, Yeager M, Burdette L, Berndt SI, Harris CC
    Int. J. Cancer. 2014 Mar; Volume 134 (Issue 6): Pages 1399-407 PUBMED
  • Innate immunity gene polymorphisms and the risk of colorectal neoplasia.
    Chang CM, Chia VM, Gunter MJ, Zanetti KA, Ryan BM, Goodman JE, Harris CC, Weissfeld J, Huang WY, Chanock S, Yeager M, Hayes RB, Berndt SI, Genetics and Epidemiology of Colorectal Cancer Consortium
    Carcinogenesis. 2013 Nov; Volume 34 (Issue 11): Pages 2512-20 PUBMED
  • Common genetic variants in the 9p21 region and their associations with multiple tumours.
    Gu F, Pfeiffer RM, Bhattacharjee S, Han SS, Taylor PR, Berndt S, Yang H, Sigurdson AJ, Toro J, Mirabello L, Greene MH, Freedman ND, Abnet CC, Dawsey SM, Hu N, Qiao YL, Ding T, Brenner AV, Garcia-Closas M, Hayes R, Brinton LA, Lissowska J, Wentzensen N, Kratz C, Moore LE, Ziegler RG, Chow WH, Savage SA, Burdette L, Yeager M, Chanock SJ, Chatterjee N, Tucker MA, Goldstein AM, Yang XR
    Br. J. Cancer. 2013 Apr; Volume 108 (Issue 6): Pages 1378-86 PUBMED
  • Prospective study of genomic hypomethylation of leukocyte DNA and colorectal cancer risk.
    Huang WY, Su LJ, Hayes RB, Moore LE, Katki HA, Berndt SI, Weissfeld JL, Yegnasubramanian S, Purdue MP
    Cancer Epidemiol. Biomarkers Prev. 2012 Nov; Volume 21 (Issue 11): Pages 2014-21 PUBMED
  • Meat-related mutagen exposure, xenobiotic metabolizing gene polymorphisms and the risk of advanced colorectal adenoma and cancer.
    Gilsing AM, Berndt SI, Ruder EH, Graubard BI, Ferrucci LM, Burdett L, Weissfeld JL, Cross AJ, Sinha R
    Carcinogenesis. 2012 Jul; Volume 33 (Issue 7): Pages 1332-9 PUBMED
  • DNA repair gene polymorphisms and tobacco smoking in the risk for colorectal adenomas.
    Gao Y, Hayes RB, Huang WY, Caporaso NE, Burdette L, Yeager M, Chanock SJ, Berndt SI
    Carcinogenesis. 2011 Jun; Volume 32 (Issue 6): Pages 882-7 PUBMED
  • Xenobiotic metabolizing genes, meat-related exposures, and risk of advanced colorectal adenoma.
    Ferrucci LM, Cross AJ, Gunter MJ, Ahn J, Mayne ST, Ma X, Chanock SJ, Yeager M, Graubard BI, Berndt SI, Huang WY, Hayes RB, Sinha R
    World Rev Nutr Diet. 2010; Volume 101: Pages 34-45 PUBMED
  • Xenobiotic metabolizing genes, meat-related exposures, and risk of advanced colorectal adenoma.
    Ferrucci LM, Cross AJ, Gunter MJ, Ahn J, Mayne ST, Ma X, Chanock SJ, Yeager M, Graubard BI, Berndt SI, Huang WY, Hayes RB, Sinha R
    J Nutrigenet Nutrigenomics. 2010; Volume 3 (Issue 4-6): Pages 170-81 PUBMED
  • Polymorphisms in the adenomatous polyposis coli (APC) gene and advanced colorectal adenoma risk.
    Wong HL, Peters U, Hayes RB, Huang WY, Schatzkin A, Bresalier RS, Velie EM, Brody LC
    Eur. J. Cancer. 2010 Sep; Volume 46 (Issue 13): Pages 2457-66 PUBMED
  • Genetic variants in frizzled-related protein (FRZB) and the risk of colorectal neoplasia.
    Berndt SI, Huang WY, Yeager M, Weissfeld JL, Chanock SJ, Hayes RB
    Cancer Causes Control. 2009 May; Volume 20 (Issue 4): Pages 487-90 PUBMED
  • Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk.
    Berndt SI, Potter JD, Hazra A, Yeager M, Thomas G, Makar KW, Welch R, Cross AJ, Huang WY, Schoen RE, Giovannucci E, Chan AT, Chanock SJ, Peters U, Hunter DJ, Hayes RB
    Hum. Mol. Genet. 2008 Sep; Volume 17 (Issue 17): Pages 2665-72 PUBMED
  • Transforming growth factor beta 1 (TGFB1) gene polymorphisms and risk of advanced colorectal adenoma.
    Berndt SI, Huang WY, Chatterjee N, Yeager M, Welch R, Chanock SJ, Weissfeld JL, Schoen RE, Hayes RB
    Carcinogenesis. 2007 Sep; Volume 28 (Issue 9): Pages 1965-70 PUBMED
  • Variants in the alpha-Methylacyl-CoA racemase gene and the association with advanced distal colorectal adenoma.
    Daugherty SE, Platz EA, Shugart YY, Fallin MD, Isaacs WB, Chatterjee N, Welch R, Huang WY, Hayes RB
    Cancer Epidemiol. Biomarkers Prev. 2007 Aug; Volume 16 (Issue 8): Pages 1536-42 PUBMED
  • Genetic variation in base excision repair genes and the prevalence of advanced colorectal adenoma.
    Berndt SI, Huang WY, Fallin MD, Helzlsouer KJ, Platz EA, Weissfeld JL, Church TR, Welch R, Chanock SJ, Hayes RB
    Cancer Res. 2007 Feb; Volume 67 (Issue 3): Pages 1395-404 PUBMED
  • Tobacco smoking and colorectal hyperplastic and adenomatous polyps.
    Ji BT, Weissfeld JL, Chow WH, Huang WY, Schoen RE, Hayes RB
    Cancer Epidemiol. Biomarkers Prev. 2006 May; Volume 15 (Issue 5): Pages 897-901 PUBMED
  • Nucleotide excision repair gene polymorphisms and risk of advanced colorectal adenoma: XPC polymorphisms modify smoking-related risk.
    Huang WY, Berndt SI, Kang D, Chatterjee N, Chanock SJ, Yeager M, Welch R, Bresalier RS, Weissfeld JL, Hayes RB
    Cancer Epidemiol. Biomarkers Prev. 2006 Feb; Volume 15 (Issue 2): Pages 306-11 PUBMED
  • GSTM1, GSTT1, and GSTP1 polymorphisms and risk of advanced colorectal adenoma.
    Moore LE, Huang WY, Chatterjee N, Gunter M, Chanock S, Yeager M, Welch B, Pinsky P, Weissfeld J, Hayes RB
    Cancer Epidemiol. Biomarkers Prev. 2005 Jul; Volume 14 (Issue 7): Pages 1823-7 PUBMED
  • CYP1A1 Val462 and NQO1 Ser187 polymorphisms, cigarette use, and risk for colorectal adenoma.
    Hou L, Chatterjee N, Huang WY, Baccarelli A, Yadavalli S, Yeager M, Bresalier RS, Chanock SJ, Caporaso NE, Ji BT, Weissfeld JL, Hayes RB
    Carcinogenesis. 2005 Jun; Volume 26 (Issue 6): Pages 1122-8 PUBMED
  • Microsomal epoxide hydrolase polymorphisms and risk for advanced colorectal adenoma.
    Huang WY, Chatterjee N, Chanock S, Dean M, Yeager M, Schoen RE, Hou LF, Berndt SI, Yadavalli S, Johnson CC, Hayes RB
    Cancer Epidemiol. Biomarkers Prev. 2005 Jan; Volume 14 (Issue 1): Pages 152-7 PUBMED