Human Genetics

, Volume 131, Issue 2, pp 217–234

Meta-analysis of new genome-wide association studies of colorectal cancer risk

  • Ulrike Peters
  • Carolyn M. Hutter
  • Li Hsu
  • Fredrick R. Schumacher
  • David V. Conti
  • Christopher S. Carlson
  • Christopher K. Edlund
  • Robert W. Haile
  • Steven Gallinger
  • Brent W. Zanke
  • Mathieu Lemire
  • Jagadish Rangrej
  • Raakhee Vijayaraghavan
  • Andrew T. Chan
  • Aditi Hazra
  • David J. Hunter
  • Jing Ma
  • Charles S. Fuchs
  • Edward L. Giovannucci
  • Peter Kraft
  • Yan Liu
  • Lin Chen
  • Shuo Jiao
  • Karen W. Makar
  • Darin Taverna
  • Stephen B. Gruber
  • Gad Rennert
  • Victor Moreno
  • Cornelia M. Ulrich
  • Michael O. Woods
  • Roger C. Green
  • Patrick S. Parfrey
  • Ross L. Prentice
  • Charles Kooperberg
  • Rebecca D. Jackson
  • Andrea Z. LaCroix
  • Bette J. Caan
  • Richard B. Hayes
  • Sonja I. Berndt
  • Stephen J. Chanock
  • Robert E. Schoen
  • Jenny Chang-Claude
  • Michael Hoffmeister
  • Hermann Brenner
  • Bernd Frank
  • Stéphane Bézieau
  • Sébastien Küry
  • Martha L. Slattery
  • John L. Hopper
  • Mark A. Jenkins
  • Loic Le Marchand
  • Noralane M. Lindor
  • Polly A. Newcomb
  • Daniela Seminara
  • Thomas J. Hudson
  • David J. Duggan
  • John D. Potter
  • Graham Casey
Original Investigation

Abstract

Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured ten SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p value range 0.02 to 1.8 × 10−8). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p < 0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p value 0.03; combined p value 7.3 × 10−5). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication p value 0.03; combined p value 1.9 × 10−4). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer.

Supplementary material

439_2011_1055_MOESM1_ESM.doc (2.7 mb)
Supplementary material 1 (DOC 2,798 kb)

References

  1. Al Olama AA, Kote-Jarai Z, Giles GG, Guy M, Morrison J, Severi G, Leongamornlert DA, Tymrakiewicz M, Jhavar S, Saunders E, Hopper JL, Southey MC, Muir KR, English DR, Dearnaley DP, rdern-Jones AT, Hall AL, O’Brien LT, Wilkinson RA, Sawyer E, Lophatananon A, Horwich A, Huddart RA, Khoo VS, Parker CC, Woodhouse CJ, Thompson A, Christmas T, Ogden C, Cooper C, Donovan JL, Hamdy FC, Neal DE, Eeles RA, Easton DF (2009) Multiple loci on 8q24 associated with prostate cancer susceptibility. Nat Genet 41:1058–1060Google Scholar
  2. Annunziato L, Pignataro G, Di Renzo GF (2004) Pharmacology of brain Na+/Ca2+ exchanger: from molecular biology to therapeutic perspectives. Pharmacol Rev 56:633–654PubMedCrossRefGoogle Scholar
  3. Bodmer W, Bonilla C (2008) Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet 40:695–701PubMedCrossRefGoogle Scholar
  4. Broderick P, Carvajal-Carmona L, Pittman AM, Webb E, Howarth K, Rowan A, Lubbe S, Spain S, Sullivan K, Fielding S, Jaeger E, Vijayakrishnan J, Kemp Z, Gorman M, Chandler I, Papaemmanuil E, Penegar S, Wood W, Sellick G, Qureshi M, Teixeira A, Domingo E, Barclay E, Martin L, Sieber O, Kerr D, Gray R, Peto J, Cazier JB, Tomlinson I, Houlston RS (2007) A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk. Nat Genet 39:1315–1317PubMedCrossRefGoogle Scholar
  5. Browning BL, Browning SR (2009) A unified approach to genotype imputation and haplotype-phase inference for large data sets of trios and unrelated individuals. Am J Hum Genet 84:210–223PubMedCrossRefGoogle Scholar
  6. Brzezicha B, Schmidt M, Makalowska I, Jarmolowski A, Pienkowska J, Szweykowska-Kulinska Z (2006) Identification of human tRNA:m5C methyltransferase catalysing intron-dependent m5C formation in the first position of the anticodon of the pre-tRNA Leu (CAA). Nucleic Acids Res 34:6034–6043PubMedCrossRefGoogle Scholar
  7. Carvajal-Carmona LG, Cazier JB, Jones AM, Howarth K, Broderick P, Pittman A, Dobbins S, Tenesa A, Farrington S, Prendergast J, Theodoratou E, Barnetson R, Conti D, Newcomb P, Hopper JL, Jenkins MA, Gallinger S, Duggan DJ, Campbell H, Kerr D, Casey G, Houlston R, Dunlop M, Tomlinson I (2011) Fine-mapping of colorectal cancer susceptibility loci at 8q23.3, 16q22.1 and 19q13.11: refinement of association signals and use of in silico analysis to suggest functional variation and unexpected candidate target genes. Hum Mol Genet 20:2879–2888Google Scholar
  8. Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, Thomas G, Hirschhorn JN, Abecasis G, Altshuler D, Bailey-Wilson JE, Brooks LD, Cardon LR, Daly M, Donnelly P, Fraumeni JF Jr, Freimer NB, Gerhard DS, Gunter C, Guttmacher AE, Guyer MS, Harris EL, Hoh J, Hoover R, Kong CA, Merikangas KR, Morton CC, Palmer LJ, Phimister EG, Rice JP, Roberts J, Rotimi C, Tucker MA, Vogan KJ, Wacholder S, Wijsman EM, Winn DM, Collins FS (2007) Replicating genotype–phenotype associations. Nature 447:655–660PubMedCrossRefGoogle Scholar
  9. Cirulli ET, Goldstein DB (2010) Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet 11:415–425PubMedCrossRefGoogle Scholar
  10. Cuadrado A, Nebreda AR (2010) Mechanisms and functions of p38 MAPK signalling. Biochem J 429:403–417PubMedCrossRefGoogle Scholar
  11. de la Chapelle A (2004) Genetic predisposition to colorectal cancer. Nat Rev Cancer 4:769–780PubMedCrossRefGoogle Scholar
  12. Dudbridge F, Gusnanto A (2008) Estimation of significance thresholds for genomewide association scans. Genet Epidemiol 32:227–234PubMedCrossRefGoogle Scholar
  13. Falush D, Stephens M, Pritchard JK (2003) Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 164:1567–1587PubMedGoogle Scholar
  14. Figueiredo JC, Lewinger JP, Song C, Campbell PT, Conti DV, Edlund CK, Duggan DJ, Rangrej J, Lemire M, Hudson T, Zanke B, Cotterchio M, Gallinger S, Jenkins M, Hopper J, Haile R, Newcomb P, Potter J, Baron JA, Marchand LL, Casey G (2011) Genotype–environment interactions in microsatellite stable/microsatellite instability-low colorectal cancer: results from a genome-wide association study. Cancer Epidemiol Biomarkers Prev 20:758–766PubMedCrossRefGoogle Scholar
  15. Freedman ML, Haiman CA, Patterson N, McDonald GJ, Tandon A, Waliszewska A, Penney K, Steen RG, Ardlie K, John EM, Oakley-Girvan I, Whittemore AS, Cooney KA, Ingles SA, Altshuler D, Henderson BE, Reich D (2006) Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men. Proc Natl Acad Sci USA 103:14068–14073PubMedCrossRefGoogle Scholar
  16. Garner C (2007) Upward bias in odds ratio estimates from genome-wide association studies. Genet Epidemiol 31:288–295PubMedCrossRefGoogle Scholar
  17. Gruber SB, Moreno V, Rozek LS, Rennert HS, Lejbkowicz F, Bonner JD, Greenson JK, Giordano TJ, Fearon ER, Rennert G (2007) Genetic variation in 8q24 associated with risk of colorectal cancer. Cancer Biol Ther 6:1143–1147Google Scholar
  18. Hardwick JC, Kodach LL, Offerhaus GJ, Van Den Brink GR (2008) Bone morphogenetic protein signalling in colorectal cancer. Nat Rev Cancer 8:806–812PubMedCrossRefGoogle Scholar
  19. Hoggart CJ, Clark TG, De Iorio IM, Whittaker JC, Balding DJ (2008) Genome-wide significance for dense SNP and resequencing data. Genet Epidemiol 32:179–185PubMedCrossRefGoogle Scholar
  20. Houlston RS, Webb E, Broderick P, Pittman AM, Di Bernardo MC, Lubbe S, Chandler I, Vijayakrishnan J, Sullivan K, Penegar S, Carvajal-Carmona L, Howarth K, Jaeger E, Spain SL, Walther A, Barclay E, Martin L, Gorman M, Domingo E, Teixeira AS, Kerr D, Cazier JB, Niittymaki I, Tuupanen S, Karhu A, Aaltonen LA, Tomlinson IPM, Farrington SM, Tenesa A, Prendergast JGD, Barnetson RA, Cetnarskyj R, Porteous ME, Pharoah PDP, Koessler T, Hampe J, Buch S, Schafmayer C, Tepel J, Schreiber S, Volzke H, Chang-Claude J, Hoffmeister M, Brenner H, Zanke BW, Montpetit A, Hudson TJ, Gallinger S, Campbell H, Dunlop MG (2008) Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer. Nat Genet 40:1426–1435PubMedCrossRefGoogle Scholar
  21. Houlston RS, Cheadle J, Dobbins SE, Tenesa A, Jones AM, Howarth K, Spain SL, Broderick P, Domingo E, Farrington S, Prendergast JG, Pittman AM, Theodoratou E, Smith CG, Olver B, Walther A, Barnetson RA, Churchman M, Jaeger EE, Penegar S, Barclay E, Martin L, Gorman M, Mager R, Johnstone E, Midgley R, Niittymaki I, Tuupanen S, Colley J, Idziaszczyk S, Thomas HJ, Lucassen AM, Evans DG, Maher ER, Maughan T, Dimas A, Dermitzakis E, Cazier JB, Aaltonen LA, Pharoah P, Kerr DJ, Carvajal-Carmona LG, Campbell H, Dunlop MG, Tomlinson IP (2010) Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33. Nat Genet 42:973–977PubMedCrossRefGoogle Scholar
  22. Howe JR, Bair JL, Sayed MG, Anderson ME, Mitros FA, Petersen GM, Velculescu VE, Traverso G, Vogelstein B (2001) Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nat Genet 28:184–187PubMedCrossRefGoogle Scholar
  23. Hsiung CA, Lan Q, Hong YC, Chen CJ, Hosgood HD, Chang IS, Chatterjee N, Brennan P, Wu C, Zheng W, Chang GC, Wu T, Park JY, Hsiao CF, Kim YH, Shen H, Seow A, Yeager M, Tsai YH, Kim YT, Chow WH, Guo H, Wang WC, Sung SW, Hu Z, Chen KY, Kim JH, Chen Y, Huang L, Lee KM, Lo YL, Gao YT, Kim JH, Liu L, Huang MS, Jung TH, Jin G, Caporaso N, Yu D, Kim CH, Su WC, Shu XO, Xu P, Kim IS, Chen YM, Ma H, Shen M, Cha SI, Tan W, Chang CH, Sung JS, Zhang M, Yang TY, Park KH, Yuenger J, Wang CL, Ryu JS, Xiang Y, Deng Q, Hutchinson A, Kim JS, Cai Q, Landi MT, Yu CJ, Park JY, Tucker M, Hung JY, Lin CC, Perng RP, Boffetta P, Chen CY, Chen KC, Yang SY, Hu CY, Chang CK, Fraumeni JF, Jr., Chanock S, Yang PC, Rothman N, Lin D (2010) The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia. PLoS Genet 6Google Scholar
  24. Hubscher U, Maga G, Spadari S (2002) Eukaryotic DNA polymerases. Annu Rev Biochem 71:133–163PubMedCrossRefGoogle Scholar
  25. Hutter CM, Slattery ML, Duggan DJ, Muehling J, Curtin K, Hsu L, Beresford SA, Rajkovic A, Sarto GE, Marshall JR, Hammad N, Wallace R, Makar KW, Prentice RL, Caan BJ, Potter JD, Peters U (2010) Characterization of the association between 8q24 and colon cancer: gene–environment exploration and meta-analysis. BMC Cancer 10:670PubMedCrossRefGoogle Scholar
  26. International HapMap Consortium (2005) A haplotype map of the human genome. Nature 437:1299–1320CrossRefGoogle Scholar
  27. Ioannidis JP, Patsopoulos NA, Evangelou E (2007) Heterogeneity in meta-analyses of genome-wide association investigations. PLoS ONE 2:e841PubMedCrossRefGoogle Scholar
  28. Johnatty SE, Beesley J, Chen X, Macgregor S, Duffy DL, Spurdle AB, de Fazio A, Gava N, Webb PM, Rossing MA, Doherty JA, Goodman MT, Lurie G, Thompson PJ, Wilkens LR, Ness RB, Moysich KB, Chang-Claude J, Wang-Gohrke S, Cramer DW, Terry KL, Hankinson SE, Tworoger SS, Garcia-Closas M, Yang H, Lissowska J, Chanock SJ, Pharoah PD, Song H, Whitemore AS, Pearce CL, Stram DO, Wu AH, Pike MC, Gayther SA, Ramus SJ, Menon U, Gentry-Maharaj A, Anton-Culver H, Ziogas A, Hogdall E, Kjaer SK, Hogdall C, Berchuck A, Schildkraut JM, Iversen ES, Moorman PG, Phelan CM, Sellers TA, Cunningham JM, Vierkant RA, Rider DN, Goode EL, Haviv I, Chenevix-Trench G (2010) Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility “hot-spot”. PLoS Genet 6:e1001016PubMedCrossRefGoogle Scholar
  29. Kraft P, Zeggini E, Ioannidis JP (2009) Replication in genome-wide association studies. Stat Sci 24:561–573PubMedCrossRefGoogle Scholar
  30. Landi MT, Chatterjee N, Yu K, Goldin LR, Goldstein AM, Rotunno M, Mirabello L, Jacobs K, Wheeler W, Yeager M, Bergen AW, Li Q, Consonni D, Pesatori AC, Wacholder S, Thun M, Diver R, Oken M, Virtamo J, Albanes D, Wang Z, Burdette L, Doheny KF, Pugh EW, Laurie C, Brennan P, Hung R, Gaborieau V, McKay JD, Lathrop M, McLaughlin J, Wang Y, Tsao MS, Spitz MR, Wang Y, Krokan H, Vatten L, Skorpen F, Arnesen E, Benhamou S, Bouchard C, Metsapalu A, Vooder T, Nelis M, Valk K, Field JK, Chen C, Goodman G, Sulem P, Thorleifsson G, Rafnar T, Eisen T, Sauter W, Rosenberger A, Bickeboller H, Risch A, Chang-Claude J, Wichmann HE, Stefansson K, Houlston R, Amos CI, Fraumeni JF Jr, Savage SA, Bertazzi PA, Tucker MA, Chanock S, Caporaso NE (2009) A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am J Hum Genet 85:679–691PubMedCrossRefGoogle Scholar
  31. Lango AH, Estrada K, Lettre G, Berndt SI, Weedon MN, Rivadeneira F, Willer CJ, Jackson AU, Vedantam S, Raychaudhuri S, Ferreira T, Wood AR, Weyant RJ, Segre AV, Speliotes EK, Wheeler E, Soranzo N, Park JH, Yang J, Gudbjartsson D, Heard-Costa NL, Randall JC, Qi L, Vernon SA, Magi R, Pastinen T, Liang L, Heid IM, Luan J, Thorleifsson G, Winkler TW, Goddard ME, Sin LK, Palmer C, Workalemahu T, Aulchenko YS, Johansson A, Carola ZM, Feitosa MF, Esko T, Johnson T, Ketkar S, Kraft P, Mangino M, Prokopenko I, Absher D, Albrecht E, Ernst F, Glazer NL, Hayward C, Hottenga JJ, Jacobs KB, Knowles JW, Kutalik Z, Monda KL, Polasek O, Preuss M, Rayner NW, Robertson NR, Steinthorsdottir V, Tyrer JP, Voight BF, Wiklund F, Xu J, Hua ZJ, Nyholt DR, Pellikka N, Perola M, Perry JR, Surakka I, Tammesoo ML, Altmaier EL, Amin N, Aspelund T, Bhangale T, Boucher G, Chasman DI, Chen C, Coin L, Cooper MN, Dixon AL, Gibson Q, Grundberg E, Hao K, Juhani JM, Kaplan LM, Kettunen J, Konig IR, Kwan T, Lawrence RW, Levinson DF, Lorentzon M, McKnight B, Morris AP, Muller M, Suh NJ, Purcell S, Rafelt S, Salem RM, Salvi E, Sanna S, Shi J, Sovio U, Thompson JR, Turchin MC, Vandenput L, Verlaan DJ, Vitart V, White CC, Ziegler A, Almgren P, Balmforth AJ, Campbell H, Citterio L, De Grandi A, Dominiczak A, Duan J, Elliott P, Elosua R, Eriksson JG, Freimer NB, Geus EJ, Glorioso N, Haiqing S, Hartikainen AL, Havulinna AS, Hicks AA, Hui J, Igl W, Illig T, Jula A, Kajantie E, Kilpelainen TO, Koiranen M, Kolcic I, Koskinen S, Kovacs P, Laitinen J, Liu J, Lokki ML, Marusic A, Maschio A, Meitinger T, Mulas A, Pare G, Parker AN, Peden JF, Petersmann A, Pichler I, Pietilainen KH, Pouta A, Ridderstrale M, Rotter JI, Sambrook JG, Sanders AR, Oliver SC, Sinisalo J, Smit JH, Stringham HM, Bragi WG, Widen E, Wild SH, Willemsen G, Zagato L, Zgaga L, Zitting P, Alavere H, Farrall M, McArdle WL, Nelis M, Peters MJ, Ripatti S, van Meurs JB, Aben KK, Ardlie KG, Beckmann JS, Beilby JP, Bergman RN, Bergmann S, Collins FS, Cusi D, den Heijer M, Eiriksdottir G, Gejman PV, Hall AS, Hamsten A, Huikuri HV, Iribarren C, Kahonen M, Kaprio J, Kathiresan S, Kiemeney L, Kocher T, Launer LJ, Lehtimaki T, Melander O, Mosley TH, Jr., Musk AW, Nieminen MS, O’Donnell CJ, Ohlsson C, Oostra B, Palmer LJ, Raitakari O, Ridker PM, Rioux JD, Rissanen A, Rivolta C, Schunkert H, Shuldiner AR, Siscovick DS, Stumvoll M, Tonjes A, Tuomilehto J, van Ommen GJ, Viikari J, Heath AC, Martin NG, Montgomery GW, Province MA, Kayser M, Arnold AM, Atwood LD, Boerwinkle E, Chanock SJ, Deloukas P, Gieger C, Gronberg H, Hall P, Hattersley AT, Hengstenberg C, Hoffman W, Mark LG, Salomaa V, Schreiber S, Uda M, Waterworth D, Wright AF, Assimes TL, Barroso I, Hofman A, Mohlke KL, Boomsma DI, Caulfield MJ, Adrienne CL, Erdmann J, Fox CS, Gudnason V, Gyllensten U, Harris TB, Hayes RB, Jarvelin MR, Mooser V, Munroe PB, Ouwehand WH (2010) Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467:832–838Google Scholar
  32. Luna A, Nicodemus KK (2007) snp.plotter: an R-based SNP/haplotype association and linkage disequilibrium plotting package. Bioinformatics 23:774–776PubMedCrossRefGoogle Scholar
  33. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll SA, Visscher PM (2009) Finding the missing heritability of complex diseases. Nature 461:747–753PubMedCrossRefGoogle Scholar
  34. Massague J (2000) How cells read TGF-beta signals. Nat Rev Mol Cell Biol 1:169–178PubMedCrossRefGoogle Scholar
  35. McKay JD, Hung RJ, Gaborieau V, Boffetta P, Chabrier A, Byrnes G, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, McLaughlin J, Shepherd F, Montpetit A, Narod S, Krokan HE, Skorpen F, Elvestad MB, Vatten L, Njolstad I, Axelsson T, Chen C, Goodman G, Barnett M, Loomis MM, Lubinski J, Matyjasik J, Lener M, Oszutowska D, Field J, Liloglou T, Xinarianos G, Cassidy A, Vineis P, Clavel-Chapelon F, Palli D, Tumino R, Krogh V, Panico S, Gonzalez CA, Ramon QJ, Martinez C, Navarro C, Ardanaz E, Larranaga N, Kham KT, Key T, Bueno-de-Mesquita HB, Peeters PH, Trichopoulou A, Linseisen J, Boeing H, Hallmans G, Overvad K, Tjonneland A, Kumle M, Riboli E, Zelenika D, Boland A, Delepine M, Foglio M, Lechner D, Matsuda F, Blanche H, Gut I, Heath S, Lathrop M, Brennan P (2008) Lung cancer susceptibility locus at 5p15.33. Nat Genet 40:1404–1406PubMedCrossRefGoogle Scholar
  36. Miki D, Kubo M, Takahashi A, Yoon KA, Kim J, Lee GK, Zo JI, Lee JS, Hosono N, Morizono T, Tsunoda T, Kamatani N, Chayama K, Takahashi T, Inazawa J, Nakamura Y, Daigo Y (2010) Variation in TP63 is associated with lung adenocarcinoma susceptibility in Japanese and Korean populations. Nat Genet 42:893–896PubMedCrossRefGoogle Scholar
  37. Minelli C, Thompson JR, Abrams KR, Thakkinstian A, Attia J (2005) The choice of a genetic model in the meta-analysis of molecular association studies. Int J Epidemiol 34:1319–1328PubMedCrossRefGoogle Scholar
  38. National Cancer Institute (2009) Cancer Genetic Markers of Susceptibility (CGEMS) data website. http://cgems.cancer.gov/data_access.html
  39. Park JH, Wacholder S, Gail MH, Peters U, Jacobs KB, Chanock SJ, Chatterjee N (2010) Estimation of effect size distribution from genome-wide association studies and implications for future discoveries. Nat Genet 42:570–575PubMedCrossRefGoogle Scholar
  40. Pe’er I, Yelensk R, Altshuler D, Daly MJ (2008) Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet Epidemiol 32:381–385PubMedCrossRefGoogle Scholar
  41. Petersen GM, Amundadottir L, Fuchs CS, Kraft P, Stolzenberg-Solomon RZ, Jacobs KB, Arslan AA, Bueno-de-Mesquita HB, Gallinger S, Gross M, Helzlsouer K, Holly EA, Jacobs EJ, Klein AP, Lacroix A, Li D, Mandelson MT, Olson SH, Risch HA, Zheng W, Albanes D, Bamlet WR, Berg CD, Boutron-Ruault MC, Buring JE, Bracci PM, Canzian F, Clipp S, Cotterchio M, de Andrade M, Duell EJ, Gaziano JM, Giovannucci EL, Goggins M, Hallmans G, Hankinson SE, Hassan M, Howard B, Hunter DJ, Hutchinson A, Jenab M, Kaaks R, Kooperberg C, Krogh V, Kurtz RC, Lynch SM, McWilliams RR, Mendelsohn JB, Michaud DS, Parikh H, Patel AV, Peeters PH, Rajkovic A, Riboli E, Rodriguez L, Seminara D, Shu XO, Thomas G, Tjonneland A, Tobias GS, Trichopoulos D, Van den Eeden SK, Virtamo J, Wactawski-Wende J, Wang Z, Wolpin BM, Yu H, Yu K, Zeleniuch-Jacquotte A, Fraumeni JF, Jr, Hoover RN, Hartge P, Chanock SJ (2010) A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet 42:224–228Google Scholar
  42. Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155:945–959PubMedGoogle Scholar
  43. Pruim RJ, Welch RP, Sanna S, Teslovich TM, Chines PS, Gliedt TP, Boehnke M, Abecasis GR, Willer CJ (2010) LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26:2336–2337PubMedCrossRefGoogle Scholar
  44. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575PubMedCrossRefGoogle Scholar
  45. R Development Core Team (2011) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, AustriaGoogle Scholar
  46. Rafnar T, Sulem P, Stacey SN, Geller F, Gudmundsson J, Sigurdsson A, Jakobsdottir M, Helgadottir H, Thorlacius S, Aben KK, Blondal T, Thorgeirsson TE, Thorleifsson G, Kristjansson K, Thorisdottir K, Ragnarsson R, Sigurgeirsson B, Skuladottir H, Gudbjartsson T, Isaksson HJ, Einarsson GV, Benediktsdottir KR, Agnarsson BA, Olafsson K, Salvarsdottir A, Bjarnason H, Asgeirsdottir M, Kristinsson KT, Matthiasdottir S, Sveinsdottir SG, Polidoro S, Hoiom V, Botella-Estrada R, Hemminki K, Rudnai P, Bishop DT, Campagna M, Kellen E, Zeegers MP, de Verdier P, Ferrer A, Isla D, Vidal MJ, Andres R, Saez B, Juberias P, Banzo J, Navarrete S, Tres A, Kan D, Lindblom A, Gurzau E, Koppova K, de Vegt F, Schalken JA, van der Heijden HF, Smit HJ, Termeer RA, Oosterwijk E, van Hooij O, Nagore E, Porru S, Steineck G, Hansson J, Buntinx F, Catalona WJ, Matullo G, Vineis P, Kiltie AE, Mayordomo JI, Kumar R, Kiemeney LA, Frigge ML, Jonsson T, Saemundsson H, Barkardottir RB, Jonsson E, Jonsson S, Olafsson JH, Gulcher JR, Masson G, Gudbjartsson DF, Kong A, Thorsteinsdottir U, Stefansson K (2009) Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet 41:221–227Google Scholar
  47. Ries LAG, Melbert D, Krapcho M, Mariotto A, Miller BA, Feuer EJ, Clegg L, Horner MJ, Howlader N, Eisner MP, Reichman M, Edwards BK (2007) SEER cancer statistics review, 1975–2004. National Cancer Institute, Bethesda, MDGoogle Scholar
  48. Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273:1516–1517PubMedCrossRefGoogle Scholar
  49. Rosenbloom KR, Dreszer TR, Pheasant M, Barber GP, Meyer LR, Pohl A, Raney BJ, Wang T, Hinrichs AS, Zweig AS, Fujita PA, Learned K, Rhead B, Smith KE, Kuhn RM, Karolchik D, Haussler D, Kent WJ (2010) ENCODE whole-genome data in the UCSC Genome Browser. Nucleic Acids Res 38:D620–D625PubMedCrossRefGoogle Scholar
  50. Schreibman IR, Baker M, Amos C, McGarrity TJ (2005) The hamartomatous polyposis syndromes: a clinical and molecular review. Am J Gastroenterol 100:476–490PubMedCrossRefGoogle Scholar
  51. Shete S, Hosking FJ, Robertson LB, Dobbins SE, Sanson M, Malmer B, Simon M, Marie Y, Boisselier B, Delattre JY, Hoang-Xuan K, El HS, Idbaih A, Zelenika D, Andersson U, Henriksson R, Bergenheim AT, Feychting M, Lonn S, Ahlbom A, Schramm J, Linnebank M, Hemminki K, Kumar R, Hepworth SJ, Price A, Armstrong G, Liu Y, Gu X, Yu R, Lau C, Schoemaker M, Muir K, Swerdlow A, Lathrop M, Bondy M, Houlston RS (2009) Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet 41:899–904PubMedCrossRefGoogle Scholar
  52. Siepel A, Bejerano G, Pedersen JS, Hinrichs AS, Hou M, Rosenbloom K, Clawson H, Spieth J, Hillier LW, Richards S, Weinstock GM, Wilson RK, Gibbs RA, Kent WJ, Miller W, Haussler D (2005) Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res 15:1034–1050PubMedCrossRefGoogle Scholar
  53. Stacey SN, Sulem P, Masson G, Gudjonsson SA, Thorleifsson G, Jakobsdottir M, Sigurdsson A, Gudbjartsson DF, Sigurgeirsson B, Benediktsdottir KR, Thorisdottir K, Ragnarsson R, Scherer D, Hemminki K, Rudnai P, Gurzau E, Koppova K, Botella-Estrada R, Soriano V, Juberias P, Saez B, Gilaberte Y, Fuentelsaz V, Corredera C, Grasa M, Hoiom V, Lindblom A, Bonenkamp JJ, van Rossum MM, Aben KK, de Vries E, Santinami M, Di Mauro MG, Maurichi A, Wendt J, Hochleitner P, Pehamberger H, Gudmundsson J, Magnusdottir DN, Gretarsdottir S, Holm H, Steinthorsdottir V, Frigge ML, Blondal T, Saemundsdottir J, Bjarnason H, Kristjansson K, Bjornsdottir G, Okamoto I, Rivoltini L, Rodolfo M, Kiemeney LA, Hansson J, Nagore E, Mayordomo JI, Kumar R, Karagas MR, Nelson HH, Gulcher JR, Rafnar T, Thorsteinsdottir U, Olafsson JH, Kong A, Stefansson K (2009) New common variants affecting susceptibility to basal cell carcinoma. Nat Genet 41:909–914Google Scholar
  54. StataCorp (2009) Stata statistical software: release 11. StataCorp LP, College Station, TXGoogle Scholar
  55. Tenesa A, Dunlop MG (2009) New insights into the aetiology of colorectal cancer from genome-wide association studies. Nat Rev Genet 10:353–358PubMedCrossRefGoogle Scholar
  56. Tenesa A, Farrington SM, Prendergast JG, Porteous ME, Walker M, Haq N, Barnetson RA, Theodoratou E, Cetnarskyj R, Cartwright N, Semple C, Clark AJ, Reid FJ, Smith LA, Kavoussanakis K, Koessler T, Pharoah PD, Buch S, Schafmayer C, Tepel J, Schreiber S, Volzke H, Schmidt CO, Hampe J, Chang-Claude J, Hoffmeister M, Brenner H, Wilkening S, Canzian F, Capella G, Moreno V, Deary IJ, Starr JM, Tomlinson IP, Kemp Z, Howarth K, Carvajal-Carmona L, Webb E, Broderick P, Vijayakrishnan J, Houlston RS, Rennert G, Ballinger D, Rozek L, Gruber SB, Matsuda K, Kidokoro T, Nakamura Y, Zanke BW, Greenwood CM, Rangrej J, Kustra R, Montpetit A, Hudson TJ, Gallinger S, Campbell H, Dunlop MG (2008) Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21. Nat Genet 40:631–637PubMedCrossRefGoogle Scholar
  57. The Institute of Cancer Research (2008) Software and databases, molecular and population genetics team, section of cancer genetics phase 1 GWAS dataGoogle Scholar
  58. Timm DE, Liu J, Baker LJ, Harris RA (2001) Crystal structure of thiamin pyrophosphokinase. J Mol Biol 310:195–204PubMedCrossRefGoogle Scholar
  59. Tomlinson I, Webb E, Carvajal-Carmona L, Broderick P, Kemp Z, Spain S, Penegar S, Chandler I, Gorman M, Wood W, Barclay E, Lubbe S, Martin L, Sellick G, Jaeger E, Hubner R, Wild R, Rowan A, Fielding S, Howarth K, Silver A, Atkin W, Muir K, Logan R, Kerr D, Johnstone E, Sieber O, Gray R, Thomas H, Peto J, Cazier JB, Houlston R (2007) A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat Genet 39:984–988PubMedCrossRefGoogle Scholar
  60. Tomlinson IP, Webb E, Carvajal-Carmona L, Broderick P, Howarth K, Pittman AM, Spain S, Lubbe S, Walther A, Sullivan K, Jaeger E, Fielding S, Rowan A, Vijayakrishnan J, Domingo E, Chandler I, Kemp Z, Qureshi M, Farrington SM, Tenesa A, Prendergast JG, Barnetson RA, Penegar S, Barclay E, Wood W, Martin L, Gorman M, Thomas H, Peto J, Bishop DT, Gray R, Maher ER, Lucassen A, Kerr D, Evans DG, Schafmayer C, Buch S, Volzke H, Hampe J, Schreiber S, John U, Koessler T, Pharoah P, van Wezel T, Morreau H, Wijnen JT, Hopper JL, Southey MC, Giles GG, Severi G, Castellvi-Bel S, Ruiz-Ponte C, Carracedo A, Castells A, Forsti A, Hemminki K, Vodicka P, Naccarati A, Lipton L, Ho JW, Cheng KK, Sham PC, Luk J, Agundez JA, Ladero JM, de la Hoya M, Caldes T, Niittymaki I, Tuupanen S, Karhu A, Aaltonen L, Cazier JB, Campbell H, Dunlop MG, Houlston RS (2008) A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3. Nat Genet 40:623–630Google Scholar
  61. Turnbull C, Rapley EA, Seal S, Pernet D, Renwick A, Hughes D, Ricketts M, Linger R, Nsengimana J, Deloukas P, Huddart RA, Bishop DT, Easton DF, Stratton MR, Rahman N (2010) Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer. Nat Genet 42:604–607PubMedCrossRefGoogle Scholar
  62. Wang Y, Broderick P, Webb E, Wu X, Vijayakrishnan J, Matakidou A, Qureshi M, Dong Q, Gu X, Chen WV, Spitz MR, Eisen T, Amos CI, Houlston RS (2008) Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet 40:1407–1409PubMedCrossRefGoogle Scholar
  63. Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661–678CrossRefGoogle Scholar
  64. Witte JS (2007) Multiple prostate cancer risk variants on 8q24. Nat Genet 39:579–580PubMedCrossRefGoogle Scholar
  65. Wu KJ, Grandori C, Amacker M, Simon-Vermot N, Polack A, Lingner J, Dalla-Favera R (1999) Direct activation of TERT transcription by c-MYC. Nat Genet 21:220–224PubMedCrossRefGoogle Scholar
  66. Yamamoto K, Okamoto A, Isonishi S, Ochiai K, Ohtake Y (2001) A novel gene, CRR9, which was up-regulated in CDDP-resistant ovarian tumor cell line, was associated with apoptosis. Biochem Biophys Res Commun 280:1148–1154PubMedCrossRefGoogle Scholar
  67. Yeager M, Orr N, Hayes RB, Jacobs KB, Kraft P, Wacholder S, Minichiello MJ, Fearnhead P, Yu K, Chatterjee N, Wang Z, Welch R, Staats BJ, Calle EE, Feigelson HS, Thun MJ, Rodriguez C, Albanes D, Virtamo J, Weinstein S, Schumacher FR, Giovannucci E, Willett WC, Cancel-Tassin G, Cussenot O, Valeri A, Andriole GL, Gelmann EP, Tucker M, Gerhard DS, Fraumeni JF Jr, Hoover R, Hunter DJ, Chanock SJ, Thomas G (2007) Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet 39:645–649PubMedCrossRefGoogle Scholar
  68. Zanke BW, Greenwood CM, Rangrej J, Kustra R, Tenesa A, Farrington SM, Prendergast J, Olschwang S, Chiang T, Crowdy E, Ferretti V, Laflamme P, Sundararajan S, Roumy S, Olivier JF, Robidoux F, Sladek R, Montpetit A, Campbell P, Bezieau S, O’shea AM, Zogopoulos G, Cotterchio M, Newcomb P, McLaughlin J, Younghusband B, Green R, Green J, Porteous ME, Campbell H, Blanche H, Sahbatou M, Tubacher E, Bonaiti-Pellie C, Buecher B, Riboli E, Kury S, Chanock SJ, Potter J, Thomas G, Gallinger S, Hudson TJ, Dunlop MG (2007) Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat Genet 39:989–994PubMedCrossRefGoogle Scholar
  69. Zeggini E, Ioannidis JP (2009) Meta-analysis in genome-wide association studies. Pharmacogenomics 10:191–201PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Ulrike Peters
    • 1
    • 2
  • Carolyn M. Hutter
    • 1
  • Li Hsu
    • 3
  • Fredrick R. Schumacher
    • 4
  • David V. Conti
    • 4
  • Christopher S. Carlson
    • 1
  • Christopher K. Edlund
    • 5
  • Robert W. Haile
    • 4
  • Steven Gallinger
    • 6
  • Brent W. Zanke
    • 7
  • Mathieu Lemire
    • 8
  • Jagadish Rangrej
    • 8
  • Raakhee Vijayaraghavan
    • 9
  • Andrew T. Chan
    • 10
    • 11
  • Aditi Hazra
    • 11
    • 12
  • David J. Hunter
    • 12
  • Jing Ma
    • 11
  • Charles S. Fuchs
    • 11
    • 13
  • Edward L. Giovannucci
    • 11
    • 14
  • Peter Kraft
    • 12
  • Yan Liu
    • 15
  • Lin Chen
    • 16
  • Shuo Jiao
    • 1
  • Karen W. Makar
    • 1
  • Darin Taverna
    • 9
  • Stephen B. Gruber
    • 17
  • Gad Rennert
    • 18
  • Victor Moreno
    • 19
  • Cornelia M. Ulrich
    • 1
    • 2
    • 20
  • Michael O. Woods
    • 21
  • Roger C. Green
    • 21
  • Patrick S. Parfrey
    • 22
  • Ross L. Prentice
    • 23
  • Charles Kooperberg
    • 23
  • Rebecca D. Jackson
    • 24
  • Andrea Z. LaCroix
    • 1
  • Bette J. Caan
    • 25
  • Richard B. Hayes
    • 26
  • Sonja I. Berndt
    • 27
  • Stephen J. Chanock
    • 27
  • Robert E. Schoen
    • 28
  • Jenny Chang-Claude
    • 29
  • Michael Hoffmeister
    • 30
  • Hermann Brenner
    • 30
  • Bernd Frank
    • 30
  • Stéphane Bézieau
    • 31
  • Sébastien Küry
    • 31
  • Martha L. Slattery
    • 32
  • John L. Hopper
    • 33
  • Mark A. Jenkins
    • 33
  • Loic Le Marchand
    • 34
  • Noralane M. Lindor
    • 35
  • Polly A. Newcomb
    • 1
  • Daniela Seminara
    • 36
  • Thomas J. Hudson
    • 8
    • 37
  • David J. Duggan
    • 9
  • John D. Potter
    • 2
    • 23
  • Graham Casey
    • 4
  1. 1.Cancer Prevention ProgramFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.Department of Epidemiology, School of Public HealthUniversity of WashingtonSeattleUSA
  3. 3.Biostatistics and Biomathematics ProgramFred Hutchinson Cancer Research CenterSeattleUSA
  4. 4.Department of Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  5. 5.Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  6. 6.Department of Surgery, Toronto General HospitalUniversity Health NetworkTorontoCanada
  7. 7.Clinical Epidemiology ProgramOttawa Hospital Research InstituteOttawaCanada
  8. 8.Ontario Institute for Cancer ResearchTorontoCanada
  9. 9.Translational Genomics Research InstitutePhoenixUSA
  10. 10.Division of Gastroenterology, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  11. 11.Channing LaboratoryBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  12. 12.Program in Molecular and Genetic Epidemiology, Department of EpidemiologyHarvard School of Public HealthBostonUSA
  13. 13.Department of Medical OncologyDana-Farber Cancer InstituteBostonUSA
  14. 14.Departments of Epidemiology and NutritionHarvard School of Public HealthBostonUSA
  15. 15.Dallas Research CenterStephens & AssociatesDallasUSA
  16. 16.Department of Health StudiesUniversity of ChicagoChicagoUSA
  17. 17.Department of Internal MedicineUniversity of MichiganAnn ArborUSA
  18. 18.Department of Community Medicine and EpidemiologyCarmel Medical Center and Technion Faculty of MedicineHaifaIsrael
  19. 19.Biostatistics and Bioinformatics UnitCatalan Institute of Oncology-IDIBELLBarcelonaSpain
  20. 20.Division of Preventive OncologyGerman Cancer Research CenterHeidelbergGermany
  21. 21.Discipline of Genetics, Faculty of MedicineMemorial University of NewfoundlandSt. John’sCanada
  22. 22.Discipline of Medicine, Faculty of MedicineMemorial University of NewfoundlandSt. John’sCanada
  23. 23.Division of Public Health SciencesFred Hutchinson Cancer Research CenterSeattleUSA
  24. 24.Division of Endocrinology, Diabetes and MetabolismOhio State UniversityColumbusUSA
  25. 25.Division of ResearchKaiser Permanente Medical Care ProgramOaklandUSA
  26. 26.Division of Epidemiology, Department of Environmental MedicineNew York University School of MedicineNew YorkUSA
  27. 27.Division of Cancer Epidemiology and Genetics, Department of Health and Human ServicesNational Cancer Institute, National Institutes of HealthBethesdaUSA
  28. 28.Department of EpidemiologyUniversity of Pittsburgh Medical CenterPittsburghUSA
  29. 29.Division of Cancer EpidemiologyGerman Cancer Research CenterHeidelbergGermany
  30. 30.Division of Clinical Epidemiology and Aging ResearchGerman Cancer Research CenterHeidelbergGermany
  31. 31.Service de Génétique Médicale, Pôle de BiologieCentre Hospitalier Universitaire (CHU) de NantesNantesFrance
  32. 32.Department of Internal MedicineUniversity of Utah Health Sciences CenterSalt Lake CityUSA
  33. 33.Centre for Molecular, Environmental, Genetic, and Analytical EpidemiologyUniversity of MelbourneMelbourneAustralia
  34. 34.Epidemiology Program, Cancer Research Center of Hawai’iUniversity of Hawai’i at ManoaHonoluluUSA
  35. 35.Department of Medical GeneticsMayo ClinicRochesterUSA
  36. 36.Division of Cancer Control and Population SciencesNational Cancer InstituteBethesdaUSA
  37. 37.Departments of Medical Biophysics and Molecular GeneticsUniversity of TorontoTorontoCanada

Personalised recommendations