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Single nucleotide polymorphisms associated with susceptibility for development of colorectal cancer: Case-control study in a Basque population


Autoři: Iker Alegria-Lertxundi aff001;  Carmelo Aguirre aff002;  Luis Bujanda aff004;  Francisco Javier Fernández aff005;  Francisco Polo aff006;  José M. Ordovás aff007;  M. Carmen Etxezarraga aff010;  Iñaki Zabalza aff012;  Mikel Larzabal aff013;  Isabel Portillo aff014;  Marian M. de Pancorbo aff002;  Leire Palencia-Madrid aff002;  Ana M. Rocandio aff001;  Marta Arroyo-Izaga aff001
Působiště autorů: Department of Pharmacy and Food Sciences, Faculty of Pharmacy, University of the Basque Country, UPV/EHU, Vitoria-Gasteiz, Spain aff001;  BIOMICs Research Group, University of the Basque Country, UPV/EHU, Vitoria-Gasteiz, Spain aff002;  Pharmacovigilance Unit, Galdakao-Usansolo Hospital, Osakidetza, Spain aff003;  Department of Gastroenterology, Donostia University Hospital / BioDonostia Institute, Biomedicine Research Networking Center - CIBER of Hepatic and Digestive Diseases (CIBERehd), University of the Basque Country, UPV/EHU, San Sebastian, Spain aff004;  Department of Gastroenterology, Galdakao-Usansolo Hospital, Osakidetza, Galdakao, Spain aff005;  Department of Gastroenterology, Basurto University Hospital, Osakidetza, Bilbao, Spain aff006;  Nutrition and Genomics Laboratory, Jean Mayer Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, United States of America aff007;  IMDEA Food, Madrid, Spain aff008;  Nutritional Genomics and Epigenomics Group, Madrid Institute for Advanced Studies (IMDEA) Food Institute, Madrid, Spain aff009;  Department of Pathology, Basurto Hospital, Osakidetza, Bilbao, Spain aff010;  Department of Physician and Surgeon Specialities, University of the Basque Country, Leioa, UPV/EHU, Spain aff011;  Department of Pathology, Galdakao-Usansolo Hospital, Osakidetza, Galdakao, Spain aff012;  Department of Pathology, Donostia University Hospital / BioDonostia Institute, Biomedicine Research Networking Center - CIBER of Hepatic and Digestive Diseases (CIBERehd), San Sebastian, Spain aff013;  Colorectal Cancer Screening Programme, The Basque Health Service, Bilbao, Spain aff014
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0225779

Souhrn

Given the significant population diversity in genetic variation, we aimed to investigate whether single nucleotide polymorphisms (SNPs) previously identified in studies of colorectal cancer (CRC) susceptibility were also relevant to the population of the Basque Country (North of Spain). We genotyped 230 CRC cases and 230 healthy controls for 48 previously reported CRC-susceptibility SNPs. Only the rs6687758 in DUPS10 exhibited a statistically significant association with CRC risk based on the crude analysis. The rs6687758 AG genotype conferred about 2.13-fold increased risk for CRC compared to the AA genotype. Moreover, we found significant associations in cases between smoking status, physical activity, and the rs6687758 SNP. The results of a Genetic Risk Score (GRS) showed that the risk alleles were more frequent in cases than controls and the score was associated with CRC in crude analysis. In conclusion, we have confirmed a CRC susceptibility locus and the existence of associations between modifiable factors and the rs6687758 SNP; moreover, the GRS was associated with CRC. However, further experimental validations are needed to establish the role of this SNP, the function of the gene identified, as well as the contribution of the interaction between environmental factors and this locusto the risk of CRC.

Klíčová slova:

Alcohol consumption – Colorectal cancer – Gene expression – Genetic loci – Introns – Molecular genetics – Physical activity – Variant genotypes


Zdroje

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality world wide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394–424. doi: 10.3322/caac.21492 30207593

2. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, et al. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer;2018. [cited 2019 Apr 4]. https://gco.iarc.fr/today

3. Castillejo A, Mata-Balaguer T, Montenegro P, Ochoa E, Lázaro R, Martínez-Cantó A, et al. The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study. BMC Cancer. 2009;9:193. doi: 10.1186/1471-2407-9-193 19538729

4. Wolf AMD, Fontham ETH, Church TR, Flowers CR, Guerra CE, LaMonte SJ, et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin. 2018;68(4):250–281. doi: 10.3322/caac.21457 29846947

5. Chen Y, Du M, Chen W, Zhu L, Wu C, Zhang Z, Wang M, Chu H, Gu D, Chen J. Polymorphism rs2682818 in miR-618 is associated with colorectal cancer susceptibility in a Han Chinese population. Cancer Med. 2018;7(4):1194–1200. doi: 10.1002/cam4.1409 29533012

6. Siegel RL, Miller KD, Jemal A. Cancerstatistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. doi: 10.3322/caac.21551 30620402

7. Marley AR, Nan H. Epidemiology of colorectal cancer. Int J Mol Epidemiol Genet. 2016;7(3):105–114. 27766137

8. Sameer AS. Colorectalcancer: molecular mutations and polymorphisms. Front Oncol. 2013;3:114. doi: 10.3389/fonc.2013.00114 23717813

9. Zhong R, Liu L, Zou L, Sheng W, Zhu B, Xiang H,et al. Genetic variations in the TGFβ signaling pathway, smoking and risk of colorectal cancer in a Chinese population. Carcinogenesis. 2013;34(4):936–42. doi: 10.1093/carcin/bgs395 23275154

10. Yang CY, Lu RH, Lin CH, Jen CH, Tung CY, Yang SH, Lin JK, Jiang JK, Lin CH. Single nucleotide polymorphisms associated with colorectal cancer susceptibility and loss of heterozygosity in a Taiwanese population. PLoS One. 2014;9(6):e100060. doi: 10.1371/journal.pone.0100060 24968322

11. Dong LM, Potter JD, White E, Ulrich CM, Cardon LR, Peters U. Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. JAMA. 2008;299(20):2423–36. doi: 10.1001/jama.299.20.2423 18505952

12. Castellví-Bel S, Abulí A, Castells A. Meta-analysis of several GWAS sets yields additional genetic susceptibility variants for colorectal cancer: first X-linked component identified. Gastroenterology. 2012;143(6):1684–5. doi: 10.1053/j.gastro.2012.10.008 23073136

13. Idigoras I, Arrospide A, Portillo I, Arana-Arri E, Martínez-Indart L, Mar J, et al. Evaluation of the colorectal cancer screening Programme in the Basque Country (Spain) and its effectiveness based on the Miscan-colon model. BMC Public Health. 2017 Aug 1;18(1):78. doi: 10.1186/s12889-017-4639-3. Erratum in: BMC Public Health. 2017;17 (1):736. 28764731

14. Carethers JM, Jung BH. Genetics and Genetic Biomarkers in Sporadic Colorectal Cancer. Gastroenterology. 2015;149(5):1177–1190.e3. doi: 10.1053/j.gastro.2015.06.047 26216840

15. Real LM, Ruiz A, Gayán J, González-Pérez A, Sáez ME, Ramírez-Lorca R, et al. A colorectal cancer susceptibility new variant at 4q26 in the Spanish population identified by genome-wide association analysis. PLoS One. 2014;9(6):e101178. doi: 10.1371/journal.pone.0101178 24978480

16. Ministerio de Sanidad, Servicios Sociales e Igualdad / Instituto Nacional de Estadística. Encuesta Nacional de Salud. España 2011/12.Madrid: Ministerio de Sanidad, Servicios Sociales e Igualdad;2012. http://www.msssi.gob.es/estadEstudios/estadisticas/sisInfSanSNS/nivelSalud.htm

17. WorldHealthOrganization (WHO). Reportof WHO consultation: Obesity: preventing and managingtheglobal epidemic.Geneva; 2000.

18. Silva Rodrigues RA, Martinez Espinosa M, Duarte Melo C, RodriguesPerracini M, Rezende Fett WC,et al. New values anthropometry for classification of nutritional status in theelderly. J NutrHealthAging. 2014;18(7):655–61. doi: 10.1007/s12603-014-0451-2 25226103

19. Rodríguez IT, Ballart JF, Pastor GC, Jordà EB, Val VA. Validation of a short questionnaire on frequency of dietaryintake: reproducibility and validity. NutrHosp. 2008;23(3):242–52. Spanish.

20. Alegria-Lertxundi I, Alvarez M, Rocandio AM, de Pancorbo MM, Arroyo-Izaga M. NutritionalAdequacy and DietQuality in ColorectalCancerPatientsPostsurgery: A PilotStudy. NutrCancer. 2016;68(4):577–88. doi: 10.1080/01635581.2016.1158299 27144653

21. Carbajal A, Sánchez-Muniz FJ. Guía de prácticas. In: García-Arias MT, García-Fernández MC, editors. Nutrición y dietética. Secretariado de Publicaciones y Medios Audiovisuales, Universidad de León; 2003. p. 1a-130a.

22. Gobierno Vasco, Departamento de Agricultura Pesca y Alimentación. Estudio cuantitativo del consumo de alimentos en la CAPV, año 2007. Vitoria-Gasteiz: Servicio Central de Publicaciones del GobiernoVasco; 2008.

23. Aranceta J, Serra Majem L, Arija V, Gil A, Martínez de Vitoria E, Ortega R, et al. Objetivos nutricionales para la poblaciónEspañola Consenso de la Sociedad Española de Nutrición Comunitaria 2011. RevEspNutr Comunitaria. 2011;17(4):178–199.

24. Domínguez-Berjón MF, Borrell C, Cano-Serral G, Esnaola S, Nolasco A, Pasarín MI, et al. Constructing a deprivation index based on census data in large Spanish cities(the MEDEA project). GacSanit. 2008;22(3):179–87.

25. Ahrens W, Bammann K, Siani A, Buchecker K, De Henauw S, Iacoviello L, Hebestreit A, Krogh V, Lissner L, Mårild S, Molnár D, Moreno LA, Pitsiladis YP, Reisch L, Tornaritis M, Veidebaum T, Pigeot I; IDEFICS Consortium. The IDEFICS cohort: design, characteristics and participation in the baseline survey. Int J Obes (Lond). 2011;35 Suppl1:S3–15. doi: 10.1038/ijo.2011.30 21483420

26. Celorrio D, Muñoz X, Amiano P, Dorronsoro M, Bujanda L, Sánchez MJ et al. Influence of Dopaminergic System Genetic Variation and LifestyleFactorsonExcessive Alcohol Consumption. Alcohol Alcohol. 2016;51(3):258–67. doi: 10.1093/alcalc/agv114 26447226

27. Piccolo SR, Abo RP, Allen-Brady K, Camp NJ, Knight S, Anderson JL,et al. Evaluation of genetic risk scores for lipid level susinggenome-widemarkers in the Framingham Heart Study. BMC Proc. 2009;3 Suppl7:S46.

28. Jung KJ, Won D, Jeon C, Kim S, Kim TI, Jee SH, et al. A colorectal cancer prediction model using traditional and genetic risk scores in Koreans. BMC Genet. 2015;16:49. doi: 10.1186/s12863-015-0207-y 25956580

29. Cornelis MC, Qi L, Zhang C, Kraft P, Manson J, Cai T, et al. Joint effects of common genetic variants on the risk for type 2 diabetes in U.S. men and women of European ancestry. Ann Intern Med. 2009;150(8):541–50. doi: 10.7326/0003-4819-150-8-200904210-00008 19380854

30. Balding DJ. A tutorial on statistical methods for population association studies. Nat Rev Genet. 2006;7(10):781–91. doi: 10.1038/nrg1916 16983374

31. Ibáñez-Sanz G, Díez-Villanueva A, Alonso MH, Rodríguez-Moranta F, Pérez-Gómez B, Bustamante M, et al. Risk Model for Colorectal Cancer in Spanish Population Using Environmental and Genetic Factors: Results from the MCC-Spain study. Sci Rep. 2017;7:43263. doi: 10.1038/srep43263 28233817

32. MacArthur J, Bowler E, Cerezo M, Gil L, Hall P, Hastings E,et al. The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Res. 2017;45(D1):D896–D901. doi: 10.1093/nar/gkw1133 27899670

33. Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017 Jul 3;45(W1):W98–W102. doi: 10.1093/nar/gkx247 28407145

34. Houlston RS, Cheadle J, Dobbins SE, Tenesa A, Jones AM, Howarth K, et al. 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. 2010;42(11):973–7. doi: 10.1038/ng.670 20972440

35. Zhang B, Shrubsole MJ, Li G, Cai Q, Edwards T, Smalley WE, et al. Association of genetic variants for colorectal cancer differs by subtypes of polyps in the colorectum. Carcinogenesis. 2012;33(12):2417–23. doi: 10.1093/carcin/bgs308 23027627

36. Carvajal-Carmona LG, Zauber AG, Jones AM, Howarth K, Wang J, Cheng T et al. Much of the genetic risk of colorectal cancer is likely to be mediated through susceptibility to adenomas. Gastroenterology. 2013;144(1):53–5. doi: 10.1053/j.gastro.2012.09.016 22999960

37. Ensembl genome database project [Internet]; 2018 https://www.ensembl.org/Homo_sapiens/Variation/Population?db=core;r=1:221991106-221992106;v=rs6687758;vdb=variation;vf=3766274

38. Wang H, Burnett T, Kono S, Haiman CA, Iwasaki M, Wilkens LR, et al. Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A. Nat Commun. 2014;5:4613. doi: 10.1038/ncomms5613 25105248

39. Dunlop MG, Dobbins SE, Farrington SM, Jones AM, Palles C, Whiffin N, et al. Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk. Nat Genet. 2012;44(7):770–6. doi: 10.1038/ng.2293 22634755

40. Abe M, Ito H, Oze I, Nomura M, Ogawa Y, Matsuo K. The more from East-Asian, the better: risk prediction of colorectal cancer risk by GWAS-identified SNPs among Japanese. J Cancer Res Clin Oncol. 2017;143(12):2481–2492. doi: 10.1007/s00432-017-2505-4 28849422

41. Duan X, Gao Y, Yang H, Feng T, Jin T, Long Y, et al. Poly morphisms in the DUSP10 gene are associated with sex-specific colorectal cancer risk in a Han population. Int J Clin Exp Pathol. 2015;8(2):2018–25. 25973098

42. Bermudez O, Pagès G, Gimond C. The dual-specificity MAP kinas phosphatases: critical roles in development and cancer. Am J Physiol Cell Physiol. 2010;299(2):C189–202. doi: 10.1152/ajpcell.00347.2009 20463170

43. Patterson KI, Brummer T, O'Brien PM, Daly RJ. Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem J. 2009;418(3):475–89. doi: 10.1042/bj20082234 19228121

44. Keyse SM. Dual-specificity MAP kinase phosphatases (MKPs) and cancer. Cancer Metastasis Rev. 2008;27(2):253–61. doi: 10.1007/s10555-008-9123-1 18330678

45. Tanoue T, Moriguchi T, Nishida E. Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5. J Biol Chem. 1999;274(28):19949–56. doi: 10.1074/jbc.274.28.19949 10391943

46. Nomura M, Shiiba K, Katagiri C, Kasugai I, Masuda K, Sato I, et al. Novel function of MKP-5/DUSP10, a phosphatase of stress-activated kinases, on ERK-dependent gene expression, and up regulation of its gene expression in colon carcinomas. Oncol Rep. 2012;28(3):931–6. doi: 10.3892/or.2012.1862 22711061

47. Fang JY, Richardson BC. The MAPK signaling pathways and colorectal cancer. Lancet Oncol. 2005;6(5):322–7. doi: 10.1016/S1470-2045(05)70168-6 15863380

48. Han J, Sun P. The pathways to tumour suppression via route p38. Trends Biochem Sci. 2007;32(8):364–71. doi: 10.1016/j.tibs.2007.06.007 17624785

49. Png CW, Weerasooriya M, Guo J, James SJ, Poh HM, Osato M, et al. DUSP10 regulates intestinal epithelial cell growth and colorectal tumorigenesis. Oncogene. 2016;35(2):206–17. doi: 10.1038/onc.2015.74 25772234

50. Jiménez-Martínez M, Stamatakis K, Fresno M. The Dual-Specificity Phosphatase 10 (DUSP10): Its Role in Cancer, Inflammation, and Immunity. Int J Mol Sci. 2019;20(7). pii: E1626. doi: 10.3390/ijms20071626 30939861

51. Song N, Shin A, Jung HS, Oh JH, Kim J. Effects of interactions between common genetic variants and smoking on colorectal cancer. BMC Cancer. 2017;17(1):869. doi: 10.1186/s12885-017-3886-0 29258461

52. Ouyang W, Ma Q, Li J, Zhang D, Ding J, Huang Y, Xing MM, et al. Benzo[a]pyrene diol-epoxide (B[a]PDE) upregulates COX-2 expression through MAPKs/AP-1 and IKK beta/NF-kappa B in mouse epidermal Cl41 cells. Mol Carcinog. 2007;46(1):32–41. doi: 10.1002/mc.20260 16921490

53. Gunathilake MN, Lee J, Cho YA, Oh JH, Chang HJ, Sohn DK, et al. Interaction between physical activity, PITX1 rs647161 genetic polymorphism and colorectal cancer risk in a Korean population: a case-control study. Oncotarget. 2018;9(7):7590–7603. doi: 10.18632/oncotarget.24136 29484135

54. Khoury-Shakour S, Gruber SB, Lejbkowicz F, Rennert HS, Raskin L, Pinchev M, et al. Recreational physical activity modifies the association between a common GH1 polymorphism and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2008;17(12):3314–8. doi: 10.1158/1055-9965.EPI-08-0062 19064544

55. Dennis DL, Waring JL, Payeur N, Cosby C, Daudt HM. Making lifestyle changes after colorectal cancer: insights for program development. Curr Oncol. 2013;20(6):e493–511. doi: 10.3747/co.20.1514 24311950

56. Dunlop MG, Tenesa A, Farrington SM, Ballereau S, Brewster DH, Koessler T, et al. Cumulative impact of common genetic variants and other risk factors on colorectal cancer risk in 42,103 individuals. Gut. 2013;62(6):871–81. doi: 10.1136/gutjnl-2011-300537 22490517

57. Phipps AI, Newcomb PA, Garcia-Albeniz X, Hutter CM, White E, Fuchs CS, et al. Association between colorectal cancer susceptibility loci and survival time after diagnosis with colorectal cancer. Gastroenterology. 2012;143(1):51–4.e4. doi: 10.1053/j.gastro.2012.04.052 22580541

58. Hindorff LA, Gillanders EM, Manolio TA. Genetic architecture of cancer and other complex diseases: lessons learned and future directions. Carcinogenesis. 2011;32(7):945–54. doi: 10.1093/carcin/bgr056 21459759

59. Wray NR, Goddard ME, Visscher PM. Prediction of individual genetic risk to disease from genome-wide association studies. Genome Res. 2007;17(10):1520–8. doi: 10.1101/gr.6665407 17785532

60. Ortlepp JR, Lauscher J, Janssens U, Minkenberg R, Hanrath P, Hoffmann R. Analysis of several hundred genetic polymorphisms may improve assessment of the individual genetic burden for coronary artery disease. Eur J Intern Med. 2002;13(8):485–492. doi: 10.1016/s0953-6205(02)00182-6 12446192

61. Fernandez-Rozadilla C, Cazier JB, Tomlinson IP, Carvajal-Carmona LG, Palles C, Lamas MJ, et al. A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12. BMC Genomics. 2013;14:55. doi: 10.1186/1471-2164-14-55 23350875

62. Kantor ED, Hutter CM, Minnier J, Berndt SI, Brenner H, Caan BJ, et al. Gene-environment interaction involving recently identified colorectal cancer susceptibility Loci. Cancer Epidemiol Biomarkers Prev. 2014;23(9):1824–33. doi: 10.1158/1055-9965.EPI-14-0062 24994789

63. Abulí A, Castells A, Bujanda L, Lozano JJ, Bessa X, Hernández C, et al. Genetic Variants associated with Colorectal Adenoma Susceptibility. PLoSOne. 2016;11(4):e0153084. doi: 10.1371/journal.pone.0153084 27078840

64. Yao K, Hua L, Wei L, Meng J, Hu J. Correlation Between CASC8, SMAD7 Polymorphisms and the Susceptibility to Colorectal Cancer: An Updated Meta-Analysis Basedon GWAS Results. Medicine (Baltimore). 2015;94(46):e1884. doi: 10.1097/MD.0000000000001884 26579801

65. Li L, Lv L, Liang Y, Shen X, Zhou S, Zhu J, et al. Association of 8q23-24 region (8q23.3 loci and 8q24.21 loci) with susceptibility to colorectal cancer: a systematic and updated meta-analysis. Int J Clin Exp Med. 2015;8(11):21001–13. 26885031

66. Hong Y, Wu G, Li W, Liu D, He K. A comprehensive meta-analysis of genetic associations between five key SNPs and colorectal cancer risk. Oncotarget. 2016 Nov 8;7(45):73945–73959. doi: 10.18632/oncotarget.12154 27661122

67. Song N, Shin A, Park JW, Kim J, Oh JH. Common risk variants for colorectal cancer: an evaluation of associations with age at cancer onset. Sci Rep. 2017;7:40644. doi: 10.1038/srep40644 28084440

68. Whiffin N, Hosking FJ, Farrington SM, Palles C, Dobbins SE, Zgaga L, et al. Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis. Hum Mol Genet. 2014;23(17):4729–37. doi: 10.1093/hmg/ddu177 24737748

69. Zhang B, Jia WH, Matsuda K, Kweon SS, Matsuo K, Xiang YB, et al. Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk. Nat Genet. 2014;46(6):533–42. doi: 10.1038/ng.2985 24836286

70. Peters U, Hutter CM, Hsu L, Schumacher FR, Conti DV, Carlson CS, et al. Meta-analysis of new genome-wide association studies of colorectal cancerrisk. Hum Genet. 2012;131(2):217–34. doi: 10.1007/s00439-011-1055-0 21761138

71. Peters U, Jiao S, Schumacher FR, Hutter CM, Aragaki AK, Baron JA, et al. Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis. Gastroenterology. 2013;144(4):799–807.e24. doi: 10.1053/j.gastro.2012.12.020 23266556

72. Jia WH, Zhang B, Matsuo K, Shin A, Xiang YB, Jee SH, et al. Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancer. Nat Genet. 2013;45(2):191–6. doi: 10.1038/ng.2505 23263487

73. Lubbe SJ, Whiffin N, Chandler I, Broderick P, Houlston RS. Relationship between 16 susceptibility loci and colorectal cancer phenotype in 3146 patients. Carcinogenesis. 2012;33(1):108–12. doi: 10.1093/carcin/bgr243 22045029

74. Houlston RS, Webb E, Broderick P, Pittman AM, Di Bernardo MC, Lubbe S, et al. Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer. Nat Genet. 2008;40(12):1426–35. doi: 10.1038/ng.262 19011631

75. Tomlinson IP, Carvajal-Carmona LG, Dobbins SE, Tenesa A, Jones AM, Howarth K, et al. Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer. PLoS Genet. 2011;7(6):e1002105. doi: 10.1371/journal.pgen.1002105 21655089

76. Kupfer SS, Skol AD, Hong E, Ludvik A, Kittles RA, Keku TO, et al. Shared and independent colorectal cancer risk alleles in TGFβ-related genes in African and European Americans. Carcinogenesis. 2014;35(9):2025–30. doi: 10.1093/carcin/bgu088 24753543

77. Broderick P, Carvajal-Carmona L, Pittman AM, Webb E, Howarth K, Rowan A, et al. A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk. Nat Genet. 2007;39(11):1315–7. doi: 10.1038/ng.2007.18 17934461


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