Article open access publication

rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology

International Journal of Molecular Sciences, MDPI, ISSN 1422-0067

Volume 19, 9, 2018

DOI:10.3390/ijms19092473, Dimensions: pub.1106273174, PMC: PMC6163881, PMID: 30134598,

Authors

Rossing, Mary Anne (10) (11)
du Bois, Andreas (21) (22)
Harter, Philipp (21) (22)
Heitz, Florian (21) (22)
Kjaer, Susanne K. (28) (29)
Giles, Graham G (30) (31) (32)
Lu, Karen (33)
Wu, Xifeng (33)
Terry, Kathryn L (38) (39)
Cramer, Daniel W. (38) (39)
Bjorge, Line (43) (44)
Krakstad, Camilla (43) (44)
Tangen, Ingvild L. (43) (44)
Aben, Katja K H (45) (46)
Le, Nhu D. (50)
Hogdall, Estrid (28) (55)
Dicks, Ed (58)
Campbell, Ian G (32) (62)
Ramus, Susan J (71) (72)
Wu, Anna H (73)
Pike, Malcolm C (42) (73)

Affiliations

Organisations

  1. (1) Medical University of South Carolina, grid.259828.c
  2. (2) Mayo Clinic, grid.66875.3a
  3. (3) Moffitt Cancer Center, grid.468198.a
  4. (4) QIMR Berghofer Medical Research Institute, grid.1049.c
  5. (5) University of California, Los Angeles, grid.19006.3e
  6. (6) Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center, 91054 Erlangen, Germany; (P.A.F.); (M.W.B.); (A.H.)
  7. (7) University of Erlangen-Nuremberg, grid.5330.5
  8. (8) KU Leuven, grid.5596.f
  9. (9) Universitair Ziekenhuis Leuven, grid.410569.f
  10. (10) Fred Hutchinson Cancer Research Center, grid.270240.3
  11. (11) University of Washington, grid.34477.33
  12. (12) University of Utah, grid.223827.e
  13. (13) University Cancer Center Hamburg, grid.412315.0
  14. (14) German Cancer Research Center, grid.7497.d
  15. (15) Roswell Park Cancer Institute, grid.240614.5
  16. (16) Cedars-Sinai Medical Center, grid.50956.3f
  17. (17) University of Hawaii at Manoa, grid.410445.0
  18. (18) Hannover Medical School, grid.10423.34
  19. (19) Byelorussian Institute for Oncology and Medical Radiology Aleksandrov N.N., Minsk 223040, Belarus;
  20. (20) Friedrich Schiller University Jena, grid.9613.d
  21. (21) Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden 65199, Germany
  22. (22) Kliniken Essen-Mitte, grid.461714.1
  23. (23) Praxis für Humangenetik, grid.461735.2
  24. (24) Helsinki University Central Hospital, grid.15485.3d
  25. (25) University of Pittsburgh Cancer Institute, grid.478063.e
  26. (26) University of Pittsburgh, grid.21925.3d
  27. (27) The University of Texas Health Science Center at Houston, grid.267308.8
  28. (28) Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Centre, DK-2100 Copenhagen, Denmark; (A.J.); (E.H.)
  29. (29) Department of Gynaecology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark; (S.K.K.); (C.H.); (L.L.)
  30. (30) Monash University, grid.1002.3
  31. (31) Cancer Council Victoria, grid.3263.4
  32. (32) University of Melbourne, grid.1008.9
  33. (33) The University of Texas MD Anderson Cancer Center, grid.240145.6
  34. (34) Texas Southern University, grid.264771.1
  35. (35) New York University Langone Medical Center, grid.240324.3
  36. (36) University of Virginia, grid.27755.32
  37. (37) Duke University, grid.26009.3d
  38. (38) Harvard University, grid.38142.3c
  39. (39) Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; (K.L.T.); (D.W.C.)
  40. (40) Brigham and Women's Hospital, grid.62560.37
  41. (41) Rutgers, The State University of New Jersey, grid.430387.b
  42. (42) Memorial Sloan Kettering Cancer Center, grid.51462.34
  43. (43) Haukeland University Hospital, grid.412008.f
  44. (44) University of Bergen, grid.7914.b
  45. (45) Radboud University Medical Centre, Radboud Institute for Health Sciences, Nijmegen 6525 EZ, The Netherlands; (L.A.K.); (K.K.H.A.)
  46. (46) Netherlands Comprehensive Cancer Organisation, grid.470266.1
  47. (47) Radboud University Medical Centre, Department of Obstetrics and Gynecology, Nijmegen 6525 GA, The Netherlands; (L.F.A.G.M.); (A.M.v.A.)
  48. (48) Oregon Health & Science University, grid.5288.7
  49. (49) University of New Mexico, grid.266832.b
  50. (50) BC Cancer Agency, grid.248762.d
  51. (51) Simon Fraser University, grid.61971.38
  52. (52) Pomeranian Medical University, grid.107950.a
  53. (53) National Cancer Institute, grid.48336.3a
  54. (54) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
  55. (55) University of Copenhagen, grid.5254.6, KU
  56. (56) Department of Radiation Oncology, Rigshospitalet, University of Copenhagen, Copenhagen DK-2100, Denmark;
  57. (57) Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen DK-2100, Denmark;
  58. (58) University of Cambridge, grid.5335.0
  59. (59) Imperial College London, grid.7445.2
  60. (60) Glasgow Royal Infirmary, grid.411714.6
  61. (61) Beatson West of Scotland Cancer Centre, grid.422301.6
  62. (62) Peter MacCallum Cancer Centre, grid.1055.1
  63. (63) University of Southampton, grid.5491.9
  64. (64) Stanford University, grid.168010.e
  65. (65) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  66. (66) University of Toronto, grid.17063.33
  67. (67) Public Health Ontario, Samuel Lunenfeld Research Institute, Toronto, ON M5T 3L9, Canada;
  68. (68) Yale University, grid.47100.32
  69. (69) University of California, Irvine, grid.266093.8
  70. (70) University College London, grid.83440.3b
  71. (71) Garvan Institute of Medical Research, grid.415306.5
  72. (72) UNSW Sydney, grid.1005.4
  73. (73) University of Southern California, grid.42505.36
  74. (74) University of Michigan, grid.214458.e
  75. (75) California State University, Fullerton, grid.253559.d
  76. (76) Medical University of Warsaw, grid.13339.3b
  77. (77) Duke University Hospital, grid.189509.c

Description

Thymidylate synthase (TYMS) is a crucial enzyme for DNA synthesis. TYMS expression is regulated by its antisense mRNA, ENOSF1. Disrupted regulation may promote uncontrolled DNA synthesis and tumor growth. We sought to replicate our previously reported association between rs495139 in the TYMS-ENOSF1 3' gene region and increased risk of mucinous ovarian carcinoma (MOC) in an independent sample. Genotypes from 24,351 controls to 15,000 women with invasive OC, including 665 MOC, were available. We estimated per-allele odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression, and meta-analysis when combining these data with our previous report. The association between rs495139 and MOC was not significant in the independent sample (OR = 1.09; 95% CI = 0.97⁻1.22; p = 0.15; N = 665 cases). Meta-analysis suggested a weak association (OR = 1.13; 95% CI = 1.03⁻1.24; p = 0.01; N = 1019 cases). No significant association with risk of other OC histologic types was observed (p = 0.05 for tumor heterogeneity). In expression quantitative trait locus (eQTL) analysis, the rs495139 allele was positively associated with ENOSF1 mRNA expression in normal tissues of the gastrointestinal system, particularly esophageal mucosa (r = 0.51, p = 1.7 × 10-28), and nonsignificantly in five MOC tumors. The association results, along with inconclusive tumor eQTL findings, suggest that a true effect of rs495139 might be small.

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Times Cited: 2

Field Citation Ratio (FCR): 0.65

Relative Citation ratio (RCR): 0.21

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