Five endometrial cancer risk loci identified through genome-wide association analysis

Nature Genetics

Volumn 48, Issue 6, 2016, Pages 667-674

  Cheng, Timothy H T ^a   Thompson, Deborah J ^f   O'Mara, Tracy A ^c   Painter, Jodie N ^c   Glubb, Dylan M ^c   Flach, Susanne ^a   Lewis, Annabelle ^a   French, Juliet D ^c   Freeman Mills, Luke ^a   Church, David ^a   Gorman, Maggie ^a   Martin, Lynn ^a   Hodgson, Shirley ^d   MWebb, Penelope ^c   Attia, John ^e,f   Holliday, Elizabeth G ^e,f   McEvoy, Mark ^f   Scott, Rodney J ^e,g,h,i   KHenders, Anjali ^c   Martin, Nicholas G ^c   Montgomery, Grant W ^c   Nyholt, Dale R ^c,j   Ahmed, Shahana ^b   Healey, Catherine S ^b   Shah, Mitul ^b   Dennis, Joe ^b   Fasching, Peter A ^k,l   Beckmann, Matthias W ^l   Hein, Alexander ^l   Ekici, Arif B ^l   Hall, Per ^m   Czene, Kamila ^m   Darabi, Hatef ^m   Li, Jingmei ^m   Dörk, Thilo ⁿ   Dürst, Matthias ^o   Hillemanns, Peter ⁿ   Runnebaum, Ingo ^o   Amant, Frederic ^p   Schrauwen, Stefanie ^p   Zhao, Hui ^q,r   Lambrechts, Diether ^q,r   Depreeuw, Jeroen ^p,q,r   Dowdy, Sean C ^s   Goode, Ellen L ^s   Fridley, Brooke L ^t   Winham, Stacey J ^s   NjØlstad, Tormund S ^u,v   Salvesen, Helga B ^u,v   Trovik, Jone ^u,v   Werner, Henrica M J ^u,v   Ashton, Katie ^e,h,i   Otton, Geoffrey ^f   Proietto, Tony ^f   Liu, Tao ^m   Mints, Miriam ^w   Tham, Emma ^m,w   Li, Mulin Jun ^x   Yip, Shun H ^x   Wang, Junwen ^s,y   KBolla, Manjeet ^b   Michailidou, Kyriaki ^b   Wang, Qin ^b   Tyrer, Jonathan P ^b   Dunlop, Malcolm ^z,aa   Houlston, Richard ^ab   Palles, Claire ^a   Hopper, John L ^ac   Peto, Julian ^ad   Swerdlow, Anthony J ^ab   Burwinkel, Barbara ^ae,af   Brenner, Hermann ^af   Meindl, Alfons ^ag   Brauch, Hiltrud ^af,ah,ai   Lindblom, Annika ^m   Chang Claude, Jenny ^af,aj   Couch, Fergus J ^s   Giles, Graham G ^ac,ak,al   Kristensen, Vessela N ^am,an,ao   Cox, Angela ^ap   MCunningham, Julie ^s   Pharoah, Paul D P ^b   Dunning, Alison M ^b   Edwards, Stacey L ^c   Easton, Douglas F ^b,j   Tomlinson, Ian ^a   Spurdle, Amanda B ^c   more..

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^d ST GEORGE S HOSPITAL   (United Kingdom)

^e JOHN HUNTER HOSPITAL   (Australia)

^f UNIVERSITY OF NEWCASTLE   (Australia)

^g JOHN HUNTER HOSPITAL   (Australia)

^h UNIVERSITY OF NEWCASTLE   (Australia)

ⁱ UNIVERSITY OF NEWCASTLE   (Australia)

^j QUEENSLAND UNIVERSITY OF TECHNOLOGY   (Australia)

^k UNIVERSITY OF CALIFORNIA   (United States)

^l UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^m KAROLINSKA INSTITUTE   (Sweden)

ⁿ HANNOVER MEDICAL SCHOOL   (Germany)

^o JENA UNIVERSITY HOSPITAL   (Germany)

^p UNIVERSITY OF LEUVEN   (Belgium)

^q DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^r UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^s MAYO CLINIC   (United States)

^t UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

^u UNIVERSITY OF BERGEN   (Norway)

^v HAUKELAND UNIVERSITY HOSPITAL   (Norway)

^w KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^x UNIVERSITY OF HONG KONG   (Hong Kong)

^y ARIZONA STATE UNIVERSITY   (United States)

^z UNIVERSITY OF EDINBURGH   (United Kingdom)

^aa WESTERN GENERAL HOSPITAL   (United Kingdom)

^ab INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^ac UNIVERSITY OF MELBOURNE   (Australia)

^ad LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

^ae UNIVERSITY OF HEIDELBERG   (Germany)

^af GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^ag TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^ah DR MARGARETE FISCHER BOSCH INSTITUTE OF CLINICAL PHARMACOLOGY   (Germany)

^ai UNIVERSITY OF TÜBINGEN   (Germany)

^aj UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^ak CANCER EPIDEMIOLOGY CENTRE   (Australia)

^al MONASH UNIVERSITY   (Australia)

^am OSLO UNIVERSITY HOSPITAL   (Norway)

^an UNIVERSITY OF OSLO   (Norway)

^ao AKERSHUS UNIVERSITY HOSPITAL   (Norway)

^ap UNIVERSITY OF SHEFFIELD   (United Kingdom)

more..

Author keywords

[No Author keywords available]

Indexed keywords

LONG UNTRANSLATED RNA;

ALLELE; ARTICLE; CANCER CELL; CANCER REGISTRY; CANCER RISK; CARCINOGENESIS; CELL CYCLE REGULATION; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; ENDOMETRIUM CANCER; FEMALE; FOLLOW UP; GENE EXPRESSION; GENE FREQUENCY; GENOME-WIDE ASSOCIATION STUDY; HELA CELL LINE; HUMAN; HUMAN CELL; IN VITRO STUDY; OVARY CANCER; PRIORITY JOURNAL; PROMOTER REGION; QUANTITATIVE TRAIT LOCUS; SINGLE NUCLEOTIDE POLYMORPHISM; UTERINE TISSUE; CHROMOSOME 8; ENDOMETRIUM TUMOR; GENETIC PREDISPOSITION; GENETICS; META ANALYSIS;

CHROMOSOMES, HUMAN, PAIR 8; ENDOMETRIAL NEOPLASMS; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; POLYMORPHISM, SINGLE NUCLEOTIDE; PROMOTER REGIONS, GENETIC;

EID: 84965053962     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.3562     Document Type: Article

References (78)

1. Siegel, R., Ma, J., Zou, Z., & Jemal, A. Cancer statistics, 2014. CA Cancer J. Clin. 64, 9-29 (2014
2. Ferlay, J., et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur. J. Cancer 49, 1374-1403 (2013
3. Gruber, S.B., Thompson, W.D., & Cancer and Steroid Hormone Study Group. A population-based study of endometrial cancer and familial risk in younger women. Cancer Epidemiol. Biomarkers Prev. 5, 411-417 (1996
4. Win, A.K., Reece, J.C., & Ryan, S. Family history and risk of endometrial cancer: a systematic review and meta-analysis. Obstet. Gynecol. 125, 89-98 (2015
5. Barrow, E., Hill, J., & Evans, D.G. Cancer risk in Lynch syndrome. Fam. Cancer 12, 229-240 (2013
6. Church, D.N., et al. DNA polymerase e and δ exonuclease domain mutations in endometrial cancer. Hum. Mol. Genet. 22, 2820-2828 (2013
7. Palles, C., et al. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat. Genet. 45, 136-144 (2013
8. Painter, J.N., et al. Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk. Hum. Mol. Genet. 24, 1478-1492 (2015
9. Thompson, D.J., et al. CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer. Endocr. Relat. Cancer 23, 77-91 (2016
10. Spurdle, A.B., et al. Genome-wide association study identifies a common variant associated with risk of endometrial cancer. Nat. Genet. 43, 451-454 (2011
11. Tenesa, A., et al. Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21. Nat. Genet. 40, 631-637 (2008
12. Tomlinson, I., et al. A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat. Genet. 39, 984-988 (2007
13. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661-678 (2007
14. Eeles, R.A., et al. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat. Genet. 45, 385-391, e1-e2 (2013
15. Michailidou, K., et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat. Genet. 45, 353-361, e1-e2 (2013
16. Pharoah, P.D., et al. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer. Nat. Genet. 45, 362-370, e1-e2 (2013
17. Sakoda, L.C., Jorgenson, E., & Witte, J.S. Turning of COGS moves forward findings for hormonally mediated cancers. Nat. Genet. 45, 345-348 (2013
18. De Vivo, I., et al. Genome-wide association study of endometrial cancer in E2C2. Hum. Genet. 133, 211-224 (2014
19. Setiawan, V.W., et al. Two estrogen-related variants in CYP19A1 and endometrial cancer risk: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium. Cancer Epidemiol. Biomarkers Prev. 18, 242-247 (2009
20. GTEx Consortium. The Genotype-Tissue Expression (GTEx) project. Nat. Genet. 45, 580-585 (2013
21. Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature 497, 67-73 (2013
22. Katoh, M., & Katoh, M. Integrative genomic analyses on HES/HEY family: Notch-independent HES1, HES3 transcription in undifferentiated ES cells, and Notch-dependent HES1, HES5, HEY1, HEY2, HEYL transcription in fetal tissues, adult tissues, or cancer. Int. J. Oncol. 31, 461-466 (2007
23. Shao, W., Halachmi, S., & Brown, M. ERAP140, a conserved tissue-specific nuclear receptor coactivator. Mol. Cell. Biol. 22, 3358-3372 (2002
24. Kiemeney, L.A., et al. Sequence variant on 8q24 confers susceptibility to urinary bladder cancer. Nat. Genet. 40, 1307-1312 (2008
25. Rothman, N., et al. A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci. Nat. Genet. 42, 978-984 (2010
26. Easton, D.F., et al. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447, 1087-1093 (2007
27. Whiffin, N., et al. Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis. Hum. Mol. Genet. 23, 4729-4737 (2014
28. Goode, E.L., et al. A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nat. Genet. 42, 874-879 (2010
29. Eeles, R.A., et al. Identification of seven new prostate cancer susceptibility loci through a genome-wide association study. Nat. Genet. 41, 1116-1121 (2009
30. Gudmundsson, J., et al. Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility. Nat. Genet. 41, 1122-1126 (2009
31. Huppi, K., Pitt, J.J., Wahlberg, B.M., & Caplen, N.J. The 8q24 gene desert: an oasis of non-coding transcriptional activity. Front. Genet. 3, 69 (2012
32. Carvajal-Carmona, L.G., et al. Candidate locus analysis of the TERT-CLPTM1L cancer risk region on chromosome 5p15 identifies multiple independent variants associated with endometrial cancer risk. Hum. Genet. 134, 231-245 (2015
33. Berlanga, J.J., Santoyo, J., & De Haro, C. Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2α kinase. Eur. J. Biochem. 265, 754-762 (1999
34. Uhlén, M., et al. Tissue-based map of the human proteome. Science 347, 1260419 (2015
35. Cantley, L.C. The phosphoinositide 3-kinase pathway. Science 296, 1655-1657 (2002
36. Slomovitz, B.M., & Coleman, R.L. The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer. Clin. Cancer Res. 18, 5856-5864 (2012
37. Cohen, Y., et al. AKT1 pleckstrin homology domain E17K activating mutation in endometrial carcinoma. Gynecol. Oncol. 116, 88-91 (2010
38. Salvesen, H.B., et al. Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation. Proc. Natl. Acad. Sci. USA 106, 4834-4839 (2009
39. Shoji, K., et al. The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas. Br. J. Cancer 101, 145-148 (2009
40. Du, W., et al. Suppression of p53 activity by Siva1. Cell Death Differ. 16, 1493-1504 (2009
41. Wang, X., et al. Siva1 inhibits p53 function by acting as an ARF E3 ubiquitin ligase. Nat. Commun. 4, 1551 (2013
42. Li, N., et al. Siva1 suppresses epithelial-mesenchymal transition and metastasis of tumor cells by inhibiting stathmin and stabilizing microtubules. Proc. Natl. Acad. Sci. USA 108, 12851-12856 (2011
43. Dun, B., et al. Mycophenolic acid inhibits migration and invasion of gastric cancer cells via multiple molecular pathways. PLoS One 8, e81702 (2013
44. Davis, H., et al. FBXW7 mutations typically found in human cancers are distinct from null alleles and disrupt lung development. J. Pathol. 224, 180-189 (2011
45. Mutter, G.L., et al. Global expression changes of constitutive and hormonally regulated genes during endometrial neoplastic transformation. Gynecol. Oncol. 83, 177-185 (2001
46. Shi, H., Zhang, Z., Wang, X., Liu, S., & Teng, C.T. Isolation and characterization of a gene encoding human Kruppel-like factor 5 (IKLF): binding to the CAAT/GT box of the mouse lactoferrin gene promoter. Nucleic Acids Res. 27, 4807-4815 (1999
47. Simmen, R.C., et al. The emerging role of Krüppel-like factors in endocrine-responsive cancers of female reproductive tissues. J. Endocrinol. 204, 223-231 (2010
48. Nandan, M.O., et al. Krüppel-like factor 5 mediates cellular transformation during oncogenic KRAS-induced intestinal tumorigenesis. Gastroenterology 134, 120-130 (2008
49. Forbes, S.A., et al. The Catalogue of Somatic Mutations in Cancer (COSMIC). Curr. Protoc. Hum. Genet. Chapter 10, Unit 10.11 (2008
50. ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447, 799-816 (2007
51. Rao, S.S., et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665-1680 (2014
52. Wang, Y., Li, X., & Hu, H. H3K4me2 reliably defines transcription factor binding regions in different cells. Genomics 103, 222-228 (2014
53. Cheng, T.H., et al. Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1. Sci. Rep. 5, 17369 (2015
54. O'Mara, T.A., et al. Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer. Endocr. Relat. Cancer 22, 851-861 (2015
55. Power, C., & Elliott, J. Cohort profile: 1958 British birth cohort (National Child Development Study). Int. J. Epidemiol. 35, 34-41 (2006
56. McEvoy, M., et al. Cohort profile: the Hunter Community Study. Int. J. Epidemiol. 39, 1452-1463 (2010
57. McGregor, B., et al. Genetic and environmental contributions to size, color, shape, and other characteristics of melanocytic naevi in a sample of adolescent twins. Genet. Epidemiol. 16, 40-53 (1999
58. Teo, Y.Y., et al. A genotype calling algorithm for the Illumina BeadArray platform. Bioinformatics 23, 2741-2746 (2007
59. Price, A.L., et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904-909 (2006
60. Purcell, S., et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559-575 (2007
61. Aulchenko, Y.S., Ripke, S., Isaacs, A., & van Duijn, C.M. GenABEL: an R library for genome-wide association analysis. Bioinformatics 23, 1294-1296 (2007
62. Clayton, D., & Leung, H.T. An R package for analysis of whole-genome association studies. Hum. Hered. 64, 45-51 (2007
63. Howie, B., Marchini, J., & Stephens, M. Genotype imputation with thousands of genomes. G3 (Bethesda) 1, 457-470 (2011
64. Delaneau, O., Zagury, J.F., & Marchini, J. Improved whole-chromosome phasing for disease and population genetic studies. Nat. Methods 10, 5-6 (2013
65. Timpson, N.J., et al. A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans. Nat. Commun. 5, 4871 (2014
66. Marchini, J., Howie, B., Myers, S., McVean, G., & Donnelly, P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat. Genet. 39, 906-913 (2007
67. Pruim, R.J., et al. LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26, 2336-2337 (2010
68. Mägi, R., & Morris, A.P. GWAMA: software for genome-wide association meta-analysis. BMC Bioinformatics 11, 288 (2010
69. Higgins, J.P., & Thompson, S.G. Quantifying heterogeneity in a meta-analysis. Stat. Med. 21, 1539-1558 (2002
70. Huedo-Medina, T.B., Sánchez-Meca, J., Marín-Martínez, F., & Botella, J. Assessing heterogeneity in meta-analysis: Q statistic or I2 index? Psychol. Methods 11, 193-206 (2006
71. Ward, L.D., & Kellis, M. HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res. 40, D930-D934 (2012
72. Boyle, A.P., et al. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res. 22, 1790-1797 (2012
73. Hnisz, D., et al. Super-enhancers in the control of cell identity and disease. Cell 155, 934-947 (2013
74. Corradin, O., et al. Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits. Genome Res. 24, 1-13 (2014
75. Livak, K.J., & Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-δδCT) method. Methods 25, 402-408 (2001
76. Giresi, P.G., Kim, J., McDaniell, R.M., Iyer, V.R., & Lieb, J.D. FAIRE (formaldehyde-assisted isolation of regulatory elements) isolates active regulatory elements from human chromatin. Genome Res. 17, 877-885 (2007
77. Ghoussaini, M., et al. Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation. Nat. Commun. 4, 4999 (2014
78. Lewis, A., et al. A polymorphic enhancer near GREM1 influences bowel cancer risk through differential CDX2 and TCF7L2 binding. Cell Rep. 8, 983-990 (2014