A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1
- 561 Downloads
Over 50 loci associated with colorectal cancer (CRC) have been uncovered by genome-wide association studies (GWAS). Identifying additional loci has the potential to help elucidate aspects of the underlying biological processes leading to better understanding of the pathogenesis of the disease. We re-evaluated a GWAS by excluding controls that have family history of CRC or personal history of colorectal polyps, as we hypothesized that their inclusion reduces power to detect associations. This is supported empirically and through simulations. Two-phase GWAS analysis was performed in a total of 16,517 cases and 14,487 controls. We identified rs17094983, a SNP associated with risk of CRC [p = 2.5 × 10−10; odds ratio estimated by re-including all controls (OR) = 0.87, 95 % confidence interval (CI) 0.83–0.91; minor allele frequency (MAF) = 13 %]. Results were replicated in samples of African descent (1894 cases and 4703 controls; p = 0.01; OR = 0.86, 95 % CI 0.77–0.97; MAF = 16 %). Gene expression data in 195 colon adenocarcinomas and 59 normal colon tissues from two different studies revealed that this locus has genotypes that are associated with RTN1 (Reticulon 1) expression (p = 0.001), a protein-coding gene involved in survival and proliferation of cancer cells which is highly expressed in normal colon tissues but has significantly reduced expression in tumor cells (p = 1.3 × 10−8).
KeywordsEndoplasmic Reticulum Stress Positive Family History Genetic Risk Score Normal Colon Tissue Expression Quantitative Trait Locus
The results shown here are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/.
ASTERISK: We are very grateful to Dr. Bruno Buecher without whom this project would not have existed. We also thank all those who agreed to participate in this study, including the patients and the healthy control persons, as well as all the physicians, technicians and students.
CANCER PREVENTION STUDY II: CPS-II is supported by the American Cancer Society (ACS). We would like to thank the CPS-II participants and the CPS-II Study Management Group for their invaluable contributions to this research. The authors would also like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, and cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program.
DACHS: We thank all participants and cooperating clinicians, and Ute Handte-Daub, Utz Benscheid, Muhabbet Celik and Ursula Eilber for excellent technical assistance.
GECCO: The authors would like to thank all those at the GECCO Coordinating Center for helping bring together the data and people that made this project possible. The authors also acknowledge COMPASS (Comprehensive Center for the Advancement of Scientific Strategies) at the Fred Hutchinson Cancer Research Center for their work harmonizing the GECCO epidemiological data set. The authors acknowledge Dave Duggan and team members at TGEN (Translational Genomics Research Institute), the Broad Institute, and the Génome Québec Innovation Center for genotyping DNA samples of cases and controls, and for scientific input for GECCO.
HPFS, NHS and PHS: We would like to acknowledge Patrice Soule and Hardeep Ranu of the Dana Farber Harvard Cancer Center High-Throughput Polymorphism Core who assisted in the genotyping for NHS, HPFS, and PHS under the supervision of Dr. Immaculata Devivo and Dr. David Hunter, Qin (Carolyn) Guo and Amit Joshi who assisted in programming for NHS and HPFS, and Haiyan Zhang who assisted in programming for the PHS. We would like to thank the participants and staff of the Nurses’ Health Study and the Health Professionals Follow-Up Study, for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data.
PLCO: The authors thank Drs. Christine Berg and Philip Prorok, Division of Cancer Prevention, National Cancer Institute, the Screening Center investigators and staff or the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, Mr. Tom Riley and staff, Information Management Services, Inc., Ms. Barbara O’Brien and staff, Westat, Inc., and Drs. Bill Kopp and staff, SAIC-Frederick. Most importantly, we acknowledge the study participants for their contributions to making this study possible. The statements contained herein are solely those of the authors and do not represent or imply concurrence or endorsement by NCI.
PMH: The authors would like to thank the study participants and staff of the Hormones and Colon Cancer study.
WHI: The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at: http://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Short%20List.pdf.
Compliance with ethical standards
GECCO: National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088; R01 CA059045).
ASTERISK: a Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Génétique and the Ligue Régionale Contre le Cancer (LRCC).
CCFR: This work was supported by grant UM1 CA167551 from the National Cancer Institute and through cooperative agreements with the following CCFR centers: 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), USC Consortium Colorectal Cancer Family Registry U01/U24 CA074799). The Colon CFR GWAS was supported by funding from the National Cancer Institute, National Institutes of Health (U01 CA122839 and R01 CA143237 to Graham Casey). CRC tumor and normal tissues used for the gene expression study were made available by The Jeremy Jass Memorial Pathology Bank. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Colon Cancer Family Registry (CCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CCFR.
COLO2&3: National Institutes of Health (R01 CA60987).
CORECT: National Cancer Institute, National Institutes of Health under RFA# CA-09-002 (U19 CA148107). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in CORECT, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or CORECT.
DACHS: German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814).
DALS: National Institutes of Health (R01 CA48998 to M. L. Slattery); HPFS is supported by the National Institutes of Health (P01 CA 055075, UM1 CA167552, R01 137178, R01 CA151993 and P50 CA127003), NHS by the National Institutes of Health (UM1 CA186107, R01 CA137178, P01 CA87969, R01 CA151993 and P50 CA127003,) and PHS by the National Institutes of Health (R01 CA042182).
MEC: National Institutes of Health (R37 CA54281, P01 CA033619, and R01 CA63464).
OFCCR: National Institutes of Health, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section above. Additional funding toward genetic analyses of OFCCR includes the Ontario Research Fund, the Canadian Institutes of Health Research, and the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation.
PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Additionally, a subset of control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS (Yeager, M et al. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet 2007 May;39(5):645–9), Colon CGEMS pancreatic cancer scan (PanScan) (Amundadottir, L et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet. 2009 Sep;41(9):986–90, and Petersen, GM et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet. 2010 Mar;42(3):224–8), and the Lung Cancer and Smoking study (Landi MT, et al. A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am J Hum Genet. 2009 Nov;85(5):679–91). The prostate and PanScan study datasets were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data/) accession numbers phs000207.v1.p1 and phs000206.v3.p2, respectively, and the lung datasets were accessed from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession number phs000093.v2.p2. Funding for the Lung Cancer and Smoking study was provided by National Institutes of Health (NIH), Genes, Environment and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446, and NIH GEI U01 HG 004438. For the lung study, the GENEVA Coordinating Center provided assistance with genotype cleaning and general study coordination, and the Johns Hopkins University Center for Inherited Disease Research conducted genotyping.
PMH: National Institutes of Health (R01 CA076366 to P.A. Newcomb).
VITAL: National Institutes of Health (K05 CA154337).
WHI: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.
- Al-Tassan NA, Whiffin N, Hosking FJ, Palles C, Farrington SM, Dobbins SE, Harris R, Gorman M, Tenesa A, Meyer BF, Wakil SM, Kinnersley B, Campbell H, Martin L, Smith CG, Idziaszczyk S, Barclay E, Maughan TS, Kaplan R, Kerr R, Kerr D, Buchannan DD, Ko Win A, Hopper J, Jenkins M, Lindor NM, Newcomb PA, Gallinger S, Conti D, Schumacher F, Casey G, Dunlop MG, Tomlinson IP, Cheadle JP, Houlston RS (2015) A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer. Sci Rep 5:10442CrossRefPubMedPubMedCentralGoogle Scholar
- Astolfi A, Nannini M, Pantaleo MA, Di Battista M, Heinrich MC, Santini D, Catena F, Corless CL, Maleddu A, Saponara M, Lolli C, Di Scioscio V, Formica S, Biasco G (2010) A molecular portrait of gastrointestinal stromal tumors: an integrative analysis of gene expression profiling and high-resolution genomic copy number. Lab Invest 90:1285–1294CrossRefPubMedGoogle Scholar
- 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, CORGI Consortium, 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 39:1315–1317CrossRefPubMedGoogle Scholar
- Dunlop MG, Dobbins SE, Farrington SM, Jones AM, Palles C, Whiffin N, Tenesa A, Spain S, Broderick P, Ooi LY, Domingo E, Smillie C, Henrion M, Frampton M, Martin L, Grimes G, Gorman M, Semple C, Ma YP, Barclay E, Prendergast J, Cazier JB, Olver B, Penegar S, Lubbe S, Chander I, Carvajal-Carmona LG, Ballereau S, Lloyd A, Vijayakrishnan J, Zgaga L, Rudan I, Theodoratou E, Colorectal Tumor Gene Identification (CORGI) Consortium, Starr JM, Deary I, Kirac I, Kovacević D, Aaltonen LA, Renkonen-Sinisalo L, Mecklin JP, Matsuda K, Nakamura Y, Okada Y, Gallinger S, Duggan DJ, Conti D, Newcomb P, Hopper J, Jenkins MA, Schumacher F, Casey G, Easton D, Shah M, Pharoah P, Lindblom A, Liu T, Swedish Low-Risk Colorectal Cancer Study Group, Smith CG, West H, Cheadle JP, COIN Collaborative Group, Midgley R, Kerr DJ, Campbell H, Tomlinson IP, Houlston RS (2012) Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk. Nat Genet 44:770–776CrossRefPubMedPubMedCentralGoogle Scholar
- 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, Niittymäki I, Tuupanen S, Colley J, Idziaszczyk S, COGENT Consortium, Thomas HJ, Lucassen AM, Evans DG, CORGI Consortium, COIN Collaborative Group, COINB Collaborative Group, 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 42:973–977CrossRefPubMedGoogle Scholar
- Houlston RS, Webb E, Broderick P, Pittman AM, Di Bernardo MC, Lubbe S, Chandler I, Vijayakrishnan J, Sullivan K, Penegar S, Colorectal Cancer Association Study Consortium, Carvajal-Carmona L, Howarth K, Jaeger E, Spain SL, Walther A, Barclay E, Martin L, Gorman M, Domingo E, Teixeira AS, CoRGI Consortium, Kerr D, Cazier JB, Niittymäki I, Tuupanen S, Karhu A, Aaltonen LA, Tomlinson IP, Farrington SM, Tenesa A, Prendergast JG, Barnetson RA, Cetnarskyj R, Porteous ME, Pharoah PD, Koessler T, Hampe J, Buch S, Schafmayer C, Tepel J, Schreiber S, Völzke 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 40:1426–1435CrossRefPubMedGoogle Scholar
- Jaeger E, Webb E, Howarth K, Carvajal-Carmona L, Rowan A, Broderick P, Walther A, Spain S, Pittman A, Kemp Z, Sullivan K, Heinimann K, Lubbe S, Domingo E, Barclay E, Martin L, Gorman M, Chandler I, Vijayakrishnan J, Wood W, Papaemmanuil E, Penegar S, Qureshi M, CORGI Consortium, Farrington S, Tenesa A, Cazier JB, Kerr D, Gray R, Peto J, Dunlop M, Campbell H, Thomas H, Houlston R, Tomlinson I (2008) Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence colorectal cancer risk. Nat Genet 40:26–28CrossRefPubMedGoogle Scholar
- 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, 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 (2013) Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancer. Nat Genet. 45:191–196CrossRefPubMedGoogle Scholar
- Levin B, Lieberman DA, McFarland B, Andrews KS, Brooks D, Bond J, Dash C, Giardiello FM, Glick S, Johnson D, Johnson CD, Levin TR, Pickhardt PJ, Rex DK, Smith RA, Thorson A, Winawer SJ, American Cancer Society Colorectal Cancer Advisory Group, US Multi-Society Task Force, American College of Radiology Colon Cancer Committee (2008) Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology 134:1570–1595CrossRefPubMedGoogle Scholar
- Levina E, Ji H, Chen M, Baig M, Oliver D, Ohouo P, Lim CU, Schools G, Carmack S, Ding Y, Broude EV, Roninson IB, Buttyan R, Shtutman M (2015) Identification of novel genes that regulate androgen receptor signaling and growth of androgen-deprived prostate cancer cells. Oncotarget 6:13088–13104CrossRefPubMedPubMedCentralGoogle Scholar
- Lieberman DA, Rex DK, Winawer SJ, Giardiello FM, Johnson DA, Levin TR, United States Multi-Society Task Force on Colorectal Cancer (2012) Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 143:844–857CrossRefPubMedGoogle Scholar
- Loo LW, Cheng I, Tiirikainen M, Lum-Jones A, Seifried A, Dunklee LM, Church JM, Gryfe R, Weisenberger DJ, Haile RW, Gallinger S, Duggan DJ, Thibodeau SN, Casey G, Le Marchand L (2012) cis-Expression QTL analysis of established colorectal cancer risk variants in colon tumors and adjacent normal tissue. PLoS One 7:e30477CrossRefPubMedPubMedCentralGoogle Scholar
- 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, 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 (2013) Identification of genetic susceptibility loci for colorectal tumors in a genome-wide meta-analysis. Gastroenterology 144:799–807CrossRefPubMedGoogle Scholar
- 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, 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 (2012) Meta-analysis of new genome-wide association studies of colorectal cancer risk. Hum Genet 131:217–234CrossRefPubMedGoogle Scholar
- Schmit SL, Schumacher FR, Edlund CK, Conti DV, Raskin L, Lejbkowicz F, Pinchev M, Rennert HS, Jenkins MA, Hopper JL, Buchanan DD, Lindor NM, Le Marchand L, Gallinger S, Haile RW, Newcomb PA, Huang SC, Rennert G, Casey G, Gruber SB (2014) A novel colorectal cancer risk locus at 4q32.2 identified from an international genome-wide association study. Carcinogenesis 35:2512–2519CrossRefPubMedPubMedCentralGoogle Scholar
- Schumacher FR, Schmit SL, Jiao S, Edlund CK, Wang H, Zhang B, Hsu L, Huang SC, Fischer CP, Harju JF, Idos GE, Lejbkowicz F, Manion FJ, McDonnell K, McNeil CE, Melas M, Rennert HS, Shi W, Thomas DC, Van Den Berg DJ, Hutter CM, Aragaki AK, Butterbach K, Caan BJ, Carlson CS, Chanock SJ, Curtis KR, Fuchs CS, Gala M, Giocannucci EL, Gogarten SM, Hayes RB, Henderson B, Hunter DJ, Jackson RD, Kolonel LN, Kooperberg C, Kury S, LaCroix A, Laurie CC, Laurie CA, Lemire M, Levine D, Ma J, Makar KW, Qu C, Taverna D, Ulrich CM, Wu K, Kono S, West DW, Berndt SI, Bezieau S, Brenner H, Campbell PT, Chan AT, Chang-Claude J, Coetzee GA, Conti DV, Duggan D, Figueiredo JC, Fortini BK, Gallinger SJ, Gauderman WJ, Giles G, Green R, Haile R, Harrison TA, Hoffmeister M, Hopper JL, Hudson TJ, Jacobs E, Iwasaki M, Jee SH, Jenkins M, Jia WH, Joshi A, Li L, Lindor NM, Matsuo K, Moreno V, Mukherjee B, Newcomb PA, Potter JD, Raskin L, Rennert G, Rosse S, Severi G, Schoen RE, Seminara D, Shu XO, Slattery ML, Tsugane S, White E, Xiang YB, Zanke BW, Zheng W, Le Marchand L, Casey G, Gruber SB, Peters U (2015) Genome-wide association study of colorectal cancer identifies six new susceptibility loci. Nat Commun. 6:7138CrossRefPubMedGoogle Scholar
- 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, Völzke 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 40:631–637CrossRefPubMedPubMedCentralGoogle Scholar
- 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, CORGI Consortium, 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 39:984–988CrossRefPubMedGoogle Scholar
- Tomlinson IP, Carvajal-Carmona LG, Dobbins SE, Tenesa A, Jones AM, Howarth K, Palles C, Broderick P, Jaeger EE, Farrington S, Lewis A, Prendergast JG, Pittman AM, Theodoratou E, Olver B, Walker M, Penegar S, Barclay E, Whiffin N, Martin L, Ballereau S, Lloyd A, Gorman M, Lubbe S, COGENT Consortium, CORGI Collaborators, EPICOLON Consortium, Howie B, Marchini J, Ruiz-Ponte C, Fernandez-Rozadilla C, Castells A, Carracedo A, Castellvi-Bel S, Duggan D, Conti D, Cazier JB, Campbell H, Sieber O, Lipton L, Gibbs P, Martin NG, Montgomery GW, Young J, Baird PN, Gallinger S, Newcomb P, Hopper J, Jenkins MA, Aaltonen LA, Kerr DJ, Cheadle J, Pharoah P, Casey G, Houlston RS, Dunlop MG (2011) Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer. PLoS Genet 7:e1002105CrossRefPubMedPubMedCentralGoogle Scholar
- 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, CORGI Consortium, Schafmayer C, Buch S, Völzke 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, Castellví-Bel S, Ruiz-Ponte C, Carracedo A, Castells A, EPICOLON Consortium, Försti A, Hemminki K, Vodicka P, Naccarati A, Lipton L, Ho JW, Cheng KK, Sham PC, Luk J, Agúndez JA, Ladero JM, de la Hoya M, Caldés T, Niittymäki 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 40:623–630CrossRefPubMedGoogle Scholar
- 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, 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 (2014) Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A. Nat Commun 5:4613PubMedPubMedCentralGoogle Scholar
- Whiffin N, Hosking FJ, Farrington SM, Palles C, Dobbins SE, Zgaga L, Lloyd A, Kinnersley B, Gorman M, Tenesa A, Broderick P, Wang Y, Barclay E, Hayward C, Martin L, Buchanan DD, Win AK, Hopper J, Jenkins M, Lindor NM, Newcomb PA, Gallinger S, Conti D, Schumacher F, Casey G, Liu T, Swedish Low-Risk Colorectal Cancer Study Group, Campbell H, Lindblom A, Houlston RS, Tomlinson IP, Dunlop MG (2014) Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis. Hum Mol Genet 23:4729–4737CrossRefPubMedPubMedCentralGoogle Scholar
- 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-Pellié 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 39:989–994CrossRefPubMedGoogle Scholar
- 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, 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 (2014) Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk. Nat Genet 46:533–542CrossRefPubMedPubMedCentralGoogle Scholar