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Genome-wide Association Study for Colon Cancer

Principal Investigator
Name
Ulrike Peters
Degrees
-
Institution
Fred Hutchinson Cancer Research Center
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2006-0285
Initial CDAS Request Approval
Sep 22, 2006
Title
Genome-wide Association Study for Colon Cancer
Summary
Since we received funding for our genome-wide association study (R01, CA059045) genotyping technologies and related costs have changed dramatically allowing us to expand the genome-wide scan to common SNPs across the genome instead of focusing only on common nonsynonymous SNPs. Accordingly, we will be able to capture a substantially larger fraction of the genetic variation in the genome, including the majority of the nonsynonymous variants. To capitalize on these advancements we propose the following modification to the original proposal which was approved to genotype 700 colon cancer cases and 700 controls of the PLCO Trial for 1,500 nonsynonymous SNPs in the second (replication) stage of a genome-wide scan for nonsynonymous SNPs: Modification: Genotype 700 colon cancer cases from the PLCO Trial for common genetic variants across the genome (about 610,000 using Illumina HumanHap 610k). To ensure a sufficient amount of DNA to genotype this increased number of SNPs we would like to request an increase in the amount of DNA from 1ug to 2 ug. We will only need DNA for the cases (and not controls) as we further propose to use existing genome-wide scan data from PLCO controls that are part of other genome-wide scans within the PLCO Trial (see Section B) and, hence, no genotyping of controls would be necessary. In addition to the PLCO samples, the following cases and controls are genotyped using the Illumina genome-wide SNP chip: 550 colon cancer cases and 700 controls from the Women's Health Initiative (WHI) Observational Study (OS) as well as about 800 colon cancer cases and 800 controls from a multi-center population-based case-control study (CCS). Most of the genotyping in the WHI OS and CCS has been completed. Depending on the availability of funds we are planning to replicate findings from this first stage in additional samples from the CCS (about 700 cases and 900 controls), samples from the WHI Clinical Trials (CT, about 900 cases and 900 controls), the Vitamin and Lifestyle Cohort Study (about 400 cases and 400 controls), and the beta-Carotene And Retinol Efficacy Trial (about 220 cases and 220 controls). Overall this study is powered to identify odds ratios of 1.24 for variants with minor allele frequency of .03 after adjusting for multiple comparisons.
Aims

The original aims of the proposal were: We propose the following primary specific aim: 1. To conduct a genome-wide association study of all common amino-acid altering SNPs to identify genes that are unequivocally associated with risk of colon cancer in a three-stage study design: a. Stage I will investigate all nsSNPs with MAF of =5% (about 20,000) in 1627 cases and 1627 controls from the multi-center population-based case-control study. b. Stage II will investigate about 1500 SNPs that are significant in stage I or selected based on other currently ongoing genome-wide scans in about 700 cases and 700 controls from the PLCO Trial. c. Stage III will investigate about 150 SNPs that meet the statistically significance in stage II in 930 cases and 930 controls from the WHI OS. As secondary aims we propose: To examine interactions between amino-acid-altering SNPs and established risk factors for colon cancer: age, smoking, use of non-steroidal anti-inflammatory drugs (NSAIDs), postmenopausal hormone use, obesity, and physical activity (gene-environment interactions). To investigate interactions between amino-acid-altering SNPs (gene-gene interactions). The proposed work is an independent investigation in PLCO, WHI, and the CCS and compliments the search for genetic variants in colon cancer carried out by Zanke et al. in Canada, with 3rd round verification in PLCO and other case-control series.

Collaborators

Richard Hayes (NCI, DCEG)
John Potter (Fred Hutchinson Cancer Research Center)
Lon Cardon (Fred Hutchinson Cancer Research Center)
Robert Schoen (University of Pittsburgh)
Ulrike Peters (Fred Hutchinson Cancer Research Center)

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  • Mendelian Randomization Study of Body Mass Index and Colorectal Cancer Risk.
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  • A model to determine colorectal cancer risk using common genetic susceptibility loci.
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    Gastroenterology. 2015 Jun; Volume 148 (Issue 7): Pages 1330-9.e14 PUBMED
  • Mendelian randomization study of height and risk of colorectal cancer.
    Thrift AP, Gong J, Peters U, Chang-Claude J, Rudolph A, Slattery ML, Chan AT, Esko T, Wood AR, Yang J, Vedantam S, Gustafsson S, Pers TH, GIANT Consortium, Baron JA, Bezieau S, Küry S, Ogino S, Berndt SI, Casey G, ...show more Haile RW, Du M, Harrison TA, Thornquist M, Duggan DJ, Le Marchand L, Lemire M, Lindor NM, Seminara D, Song M, Thibodeau SN, Cotterchio M, Win AK, Jenkins MA, Hopper JL, Ulrich CM, Potter JD, Newcomb PA, Schoen RE, Hoffmeister M, Brenner H, White E, Hsu L, Campbell PT
    Int J Epidemiol. 2015 Apr; Volume 44 (Issue 2): Pages 662-72 PUBMED
  • Association of aspirin and NSAID use with risk of colorectal cancer according to genetic variants.
    Nan H, Hutter CM, Lin Y, Jacobs EJ, Ulrich CM, White E, Baron JA, Berndt SI, Brenner H, Butterbach K, Caan BJ, Campbell PT, Carlson CS, Casey G, Chang-Claude J, Chanock SJ, Cotterchio M, Duggan D, Figueiredo JC, Fuchs CS, ...show more Giovannucci EL, Gong J, Haile RW, Harrison TA, Hayes RB, Hoffmeister M, Hopper JL, Hudson TJ, Jenkins MA, Jiao S, Lindor NM, Lemire M, Le Marchand L, Newcomb PA, Ogino S, Pflugeisen BM, Potter JD, Qu C, Rosse SA, Rudolph A, Schoen RE, Schumacher FR, Seminara D, Slattery ML, Thibodeau SN, Thomas F, Thornquist M, Warnick GS, Zanke BW, Gauderman WJ, Peters U, Hsu L, Chan AT, CCFR, GECCO
    JAMA. 2015 Mar; Volume 313 (Issue 11): Pages 1133-42 PUBMED
  • Red meat intake, NAT2, and risk of colorectal cancer: a pooled analysis of 11 studies.
    Ananthakrishnan AN, Du M, Berndt SI, Brenner H, Caan BJ, Casey G, Chang-Claude J, Duggan D, Fuchs CS, Gallinger S, Giovannucci EL, Harrison TA, Hayes RB, Hoffmeister M, Hopper JL, Hou L, Hsu L, Jenkins MA, Kraft P, Ma J, ...show more Nan H, Newcomb PA, Ogino S, Potter JD, Seminara D, Slattery ML, Thornquist M, White E, Wu K, Peters U, Chan AT
    Cancer Epidemiol. Biomarkers Prev. 2015 Jan; Volume 24 (Issue 1): Pages 198-205 PUBMED
  • No evidence of gene-calcium interactions from genome-wide analysis of colorectal cancer risk.
    Du M, Zhang X, Hoffmeister M, Schoen RE, Baron JA, Berndt SI, Brenner H, Carlson CS, Casey G, Chan AT, Curtis KR, Duggan D, Gauderman WJ, Giovannucci EL, Gong J, Harrison TA, Hayes RB, Henderson BE, Hopper JL, Hsu L, ...show more Hudson TJ, Hutter CM, Jenkins MA, Jiao S, Kocarnik JM, Kolonel LN, Le Marchand L, Lin Y, Newcomb PA, Rudolph A, Seminara D, Thornquist MD, Ulrich CM, White E, Wu K, Zanke BW, Campbell PT, Slattery ML, Peters U, Chang-Claude J, Potter JD, Colon Cancer Family Registry and Genetics and Epidemiology of Colorectal Cancer Consortium
    Cancer Epidemiol. Biomarkers Prev. 2014 Dec; Volume 23 (Issue 12): Pages 2971-6 PUBMED
  • Gene-environment interaction involving recently identified colorectal cancer susceptibility Loci.
    Kantor ED, Hutter CM, Minnier J, Berndt SI, Brenner H, Caan BJ, Campbell PT, Carlson CS, Casey G, Chan AT, Chang-Claude J, Chanock SJ, Cotterchio M, Du M, Duggan D, Fuchs CS, Giovannucci EL, Gong J, Harrison TA, Hayes RB, ...show more Henderson BE, Hoffmeister M, Hopper JL, Jenkins MA, Jiao S, Kolonel LN, Le Marchand L, Lemire M, Ma J, Newcomb PA, Ochs-Balcom HM, Pflugeisen BM, Potter JD, Rudolph A, Schoen RE, Seminara D, Slattery ML, Stelling DL, Thomas F, Thornquist M, Ulrich CM, Warnick GS, Zanke BW, Peters U, Hsu L, White E
    Cancer Epidemiol. Biomarkers Prev. 2014 Sep; Volume 23 (Issue 9): Pages 1824-33 PUBMED
  • Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A.
    Wang H, Burnett T, Kono S, Haiman CA, Iwasaki M, Wilkens LR, Loo LW, Van Den Berg D, Kolonel LN, Henderson BE, Keku TO, Sandler RS, Signorello LB, Blot WJ, Newcomb PA, Pande M, Amos CI, West DW, Bézieau S, Berndt SI, ...show more Zanke BW, Hsu L, Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Lindor NM, Haile RW, Hopper JL, Jenkins MA, Gallinger S, Casey G, Colon Cancer Family Registry (CCFR), Stenzel SL, Schumacher FR, Peters U, Gruber SB, Colorectal Transdisciplinary Study (CORECT), Tsugane S, Stram DO, Le Marchand L
    Nat Commun. 2014 Aug; Volume 5: Pages 4613 PUBMED
  • Estimating the heritability of colorectal cancer.
    Jiao S, Peters U, Berndt S, Brenner H, Butterbach K, Caan BJ, Carlson CS, Chan AT, Chang-Claude J, Chanock S, Curtis KR, Duggan D, Gong J, Harrison TA, Hayes RB, Henderson BE, Hoffmeister M, Kolonel LN, Le Marchand L, Potter JD, ...show more Rudolph A, Schoen RE, Seminara D, Slattery ML, White E, Hsu L
    Hum. Mol. Genet. 2014 Jul; Volume 23 (Issue 14): Pages 3898-905 PUBMED
  • Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.
    Zhang B, Jia WH, Matsuda K, Kweon SS, Matsuo K, Xiang YB, Shin A, Jee SH, Kim DH, Cai Q, Long J, Shi J, Wen W, Yang G, Zhang Y, Li C, Li B, Guo Y, Ren Z, Ji BT, ...show more Pan ZZ, Takahashi A, Shin MH, Matsuda F, Gao YT, Oh JH, Kim S, Ahn YO, Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Chan AT, Chang-Claude J, Slattery ML, Colorectal Transdisciplinary (CORECT) Study, Gruber SB, Schumacher FR, Stenzel SL, Colon Cancer Family Registry (CCFR), Casey G, Kim HR, Jeong JY, Park JW, Li HL, Hosono S, Cho SH, Kubo M, Shu XO, Zeng YX, Zheng W
    Nat. Genet. 2014 Jun; Volume 46 (Issue 6): Pages 533-42 PUBMED
  • Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia.
    Cheng I, Kocarnik JM, Dumitrescu L, Lindor NM, Chang-Claude J, Avery CL, Caberto CP, Love SA, Slattery ML, Chan AT, Baron JA, Hindorff LA, Park SL, Schumacher FR, Hoffmeister M, Kraft P, Butler AM, Duggan DJ, Hou L, Carlson CS, ...show more Monroe KR, Lin Y, Carty CL, Mann S, Ma J, Giovannucci EL, Fuchs CS, Newcomb PA, Jenkins MA, Hopper JL, Haile RW, Conti DV, Campbell PT, Potter JD, Caan BJ, Schoen RE, Hayes RB, Chanock SJ, Berndt SI, Küry S, Bézieau S, Ambite JL, Kumaraguruparan G, Richardson DM, Goodloe RJ, Dilks HH, Baker P, Zanke BW, Lemire M, Gallinger S, Hsu L, Jiao S, Harrison TA, Seminara D, Haiman CA, Kooperberg C, Wilkens LR, Hutter CM, White E, Crawford DC, Heiss G, Hudson TJ, Brenner H, Bush WS, Casey G, Le Marchand L, Peters U
    Gut. 2014 May; Volume 63 (Issue 5): Pages 800-7 PUBMED
  • Genome-wide diet-gene interaction analyses for risk of colorectal cancer.
    Figueiredo JC, Hsu L, Hutter CM, Lin Y, Campbell PT, Baron JA, Berndt SI, Jiao S, Casey G, Fortini B, Chan AT, Cotterchio M, Lemire M, Gallinger S, Harrison TA, Le Marchand L, Newcomb PA, Slattery ML, Caan BJ, Carlson CS, ...show more Zanke BW, Rosse SA, Brenner H, Giovannucci EL, Wu K, Chang-Claude J, Chanock SJ, Curtis KR, Duggan D, Gong J, Haile RW, Hayes RB, Hoffmeister M, Hopper JL, Jenkins MA, Kolonel LN, Qu C, Rudolph A, Schoen RE, Schumacher FR, Seminara D, Stelling DL, Thibodeau SN, Thornquist M, Warnick GS, Henderson BE, Ulrich CM, Gauderman WJ, Potter JD, White E, Peters U, CCFR, GECCO
    PLoS Genet. 2014 Apr; Volume 10 (Issue 4): Pages e1004228 PUBMED
  • Phospholipase A2G1B polymorphisms and risk of colorectal neoplasia.
    Abbenhardt C, Poole EM, Kulmacz RJ, Xiao L, Curtin K, Galbraith RL, Duggan D, Hsu L, Makar KW, Caan BJ, Koepl L, Owen RW, Scherer D, Carlson CS, Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and CCFR, Potter JD, Slattery ML, Ulrich CM
    Int J Mol Epidemiol Genet. 2013; Volume 4 (Issue 3): Pages 140-9 PUBMED
  • Fine-mapping of genome-wide association study-identified risk loci for colorectal cancer in African Americans.
    Wang H, Haiman CA, Burnett T, Fortini BK, Kolonel LN, Henderson BE, Signorello LB, Blot WJ, Keku TO, Berndt SI, Newcomb PA, Pande M, Amos CI, West DW, Casey G, Sandler RS, Haile R, Stram DO, Le Marchand L
    Hum. Mol. Genet. 2013 Dec; Volume 22 (Issue 24): Pages 5048-55 PUBMED
  • Genetic predictors of circulating 25-hydroxyvitamin d and risk of colorectal cancer.
    Hiraki LT, Qu C, Hutter CM, Baron JA, Berndt SI, Bézieau S, Brenner H, Caan BJ, Casey G, Chang-Claude J, Chanock SJ, Conti DV, Duggan D, Fuchs CS, Gallinger S, Giovannucci EL, Harrison TA, Hayes RB, Hazra A, Henderson B, ...show more Hoffmeister M, Hopper JL, Hudson TJ, Jenkins MA, Küry S, Le Marchand L, Lemire M, Ma J, Manson JE, Nan H, Newcomb PA, Ng K, Potter JD, Schoen RE, Schumacher FR, Seminara D, Slattery ML, Wactawski-Wende J, White E, Wu K, Zanke BW, Kraft P, Peters U, Chan AT
    Cancer Epidemiol. Biomarkers Prev. 2013 Nov; Volume 22 (Issue 11): Pages 2037-46 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
  • SBERIA: set-based gene-environment interaction test for rare and common variants in complex diseases.
    Jiao S, Hsu L, Bézieau S, Brenner H, Chan AT, Chang-Claude J, Le Marchand L, Lemire M, Newcomb PA, Slattery ML, Peters U
    Genet. Epidemiol. 2013 Jul; Volume 37 (Issue 5): Pages 452-64 PUBMED
  • Genome-wide association study of serum selenium concentrations.
    Gong J, Hsu L, Harrison T, King IB, Stürup S, Song X, Duggan D, Liu Y, Hutter C, Chanock SJ, Eaton CB, Marshall JR, Peters U
    Nutrients. 2013 May; Volume 5 (Issue 5): Pages 1706-18 PUBMED
  • Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis.
    Peters U, Jiao S, Schumacher FR, Hutter CM, Aragaki AK, Baron JA, Berndt SI, Bézieau S, Brenner H, Butterbach K, Caan BJ, Campbell PT, Carlson CS, Casey G, Chan AT, Chang-Claude J, Chanock SJ, Chen LS, Coetzee GA, Coetzee SG, ...show more Conti DV, Curtis KR, Duggan D, Edwards T, Fuchs CS, Gallinger S, Giovannucci EL, Gogarten SM, Gruber SB, Haile RW, Harrison TA, Hayes RB, Henderson BE, Hoffmeister M, Hopper JL, Hudson TJ, Hunter DJ, Jackson RD, Jee SH, Jenkins MA, Jia WH, Kolonel LN, Kooperberg C, Küry S, Lacroix AZ, Laurie CC, Laurie CA, Le Marchand L, Lemire M, Levine D, Lindor NM, Liu Y, Ma J, Makar KW, Matsuo K, Newcomb PA, Potter JD, Prentice RL, Qu C, Rohan T, Rosse SA, Schoen RE, Seminara D, Shrubsole M, Shu XO, Slattery ML, Taverna D, Thibodeau SN, Ulrich CM, White E, Xiang Y, Zanke BW, Zeng YX, Zhang B, Zheng W, Hsu L, Colon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium
    Gastroenterology. 2013 Apr; Volume 144 (Issue 4): Pages 799-807.e24 PUBMED
  • Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancer.
    Jia WH, Zhang B, Matsuo K, Shin A, Xiang YB, Jee SH, Kim DH, Ren Z, Cai Q, Long J, Shi J, Wen W, Yang G, Delahanty RJ, Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Colon Cancer Family Registry (CCFR), Ji BT, Pan ZZ, Matsuda F, Gao YT, ...show more Oh JH, Ahn YO, Park EJ, Li HL, Park JW, Jo J, Jeong JY, Hosono S, Casey G, Peters U, Shu XO, Zeng YX, Zheng W
    Nat. Genet. 2013 Feb; Volume 45 (Issue 2): Pages 191-6 PUBMED
  • Genome-wide search for gene-gene interactions in colorectal cancer.
    Jiao S, Hsu L, Berndt S, Bézieau S, Brenner H, Buchanan D, Caan BJ, Campbell PT, Carlson CS, Casey G, Chan AT, Chang-Claude J, Chanock S, Conti DV, Curtis KR, Duggan D, Gallinger S, Gruber SB, Harrison TA, Hayes RB, ...show more Henderson BE, Hoffmeister M, Hopper JL, Hudson TJ, Hutter CM, Jackson RD, Jenkins MA, Kantor ED, Kolonel LN, Küry S, Le Marchand L, Lemire M, Newcomb PA, Potter JD, Qu C, Rosse SA, Schoen RE, Schumacher FR, Seminara D, Slattery ML, Ulrich CM, Zanke BW, Peters U
    PLoS ONE. 2012; Volume 7 (Issue 12): Pages e52535 PUBMED
  • A pooled analysis of smoking and colorectal cancer: timing of exposure and interactions with environmental factors.
    Gong J, Hutter C, Baron JA, Berndt S, Caan B, Campbell PT, Casey G, Chan AT, Cotterchio M, Fuchs CS, Gallinger S, Giovannucci E, Harrison T, Hayes R, Hsu L, Jiao S, Lin Y, Lindor NM, Newcomb P, Pflugeisen B, ...show more Phipps AI, Rohan T, Schoen R, Seminara D, Slattery ML, Stelling D, Thomas F, Warnick G, White E, Potter J, Peters U
    Cancer Epidemiol. Biomarkers Prev. 2012 Nov; Volume 21 (Issue 11): Pages 1974-85 PUBMED
  • Characterization of gene-environment interactions for colorectal cancer susceptibility loci.
    Hutter CM, Chang-Claude J, Slattery ML, Pflugeisen BM, Lin Y, Duggan D, Nan H, Lemire M, Rangrej J, Figueiredo JC, Jiao S, Harrison TA, Liu Y, Chen LS, Stelling DL, Warnick GS, Hoffmeister M, Küry S, Fuchs CS, Giovannucci E, ...show more Hazra A, Kraft P, Hunter DJ, Gallinger S, Zanke BW, Brenner H, Frank B, Ma J, Ulrich CM, White E, Newcomb PA, Kooperberg C, LaCroix AZ, Prentice RL, Jackson RD, Schoen RE, Chanock SJ, Berndt SI, Hayes RB, Caan BJ, Potter JD, Hsu L, Bézieau S, Chan AT, Hudson TJ, Peters U
    Cancer Res. 2012 Apr; Volume 72 (Issue 8): Pages 2036-44 PUBMED
  • Meta-analysis of new genome-wide association studies of colorectal cancer risk.
    Peters U, Hutter CM, Hsu L, Schumacher FR, Conti DV, Carlson CS, Edlund CK, Haile RW, Gallinger S, Zanke BW, Lemire M, Rangrej J, Vijayaraghavan R, Chan AT, Hazra A, Hunter DJ, Ma J, Fuchs CS, Giovannucci EL, Kraft P, ...show more Liu Y, Chen L, Jiao S, Makar KW, Taverna D, Gruber SB, Rennert G, Moreno V, Ulrich CM, Woods MO, Green RC, Parfrey PS, Prentice RL, Kooperberg C, Jackson RD, Lacroix AZ, Caan BJ, Hayes RB, Berndt SI, Chanock SJ, Schoen RE, Chang-Claude J, Hoffmeister M, Brenner H, Frank B, Bézieau S, Küry S, Slattery ML, Hopper JL, Jenkins MA, Le Marchand L, Lindor NM, Newcomb PA, Seminara D, Hudson TJ, Duggan DJ, Potter JD, Casey G
    Hum. Genet. 2012 Feb; Volume 131 (Issue 2): Pages 217-34 PUBMED
  • The use of imputed values in the meta-analysis of genome-wide association studies.
    Jiao S, Hsu L, Hutter CM, Peters U
    Genet. Epidemiol. 2011 Nov; Volume 35 (Issue 7): Pages 597-605 PUBMED
  • Characterization of 9p24 risk locus and colorectal adenoma and cancer: gene-environment interaction and meta-analysis.
    Kocarnik JD, Hutter CM, Slattery ML, Berndt SI, Hsu L, Duggan DJ, Muehling J, Caan BJ, Beresford SA, Rajkovic A, Sarto GE, Marshall JR, Hammad N, Wallace RB, Makar KW, Prentice RL, Potter JD, Hayes RB, Peters U
    Cancer Epidemiol. Biomarkers Prev. 2010 Dec; Volume 19 (Issue 12): Pages 3131-9 PUBMED
  • Insights into colon cancer etiology via a regularized approach to gene set analysis of GWAS data.
    Chen LS, Hutter CM, Potter JD, Liu Y, Prentice RL, Peters U, Hsu L
    Am. J. Hum. Genet. 2010 Jun; Volume 86 (Issue 6): Pages 860-71 PUBMED