Article open access publication

DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

PLOS Genetics, Public Library of Science (PLoS), ISSN 1553-7390

Volume 10, 4, 2014

DOI:10.1371/journal.pgen.1004256, Dimensions: pub.1026278133, PMC: PMC3974638, PMID: 24698998,

Authors

Osorio, Ana (1) (2)
SWE-BRCA (15)
Eeles, Ros (45)
Side, Lucy (56)
HEBON (87)
Healey, Sue (103)
Robson, Mark (108)
Kauff, Noah (108)
Andrulis, Irene (113) (114)
Mulligan, Anna Marie (114) (115)
Sunde, Lone (119)
Benitez, Javier (1) (2)

Affiliations

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  1. (1) Centre for Biomedical Network Research on Rare Diseases, grid.452372.5
  2. (2) Spanish National Cancer Research Centre, grid.7719.8
  3. (3) Cancer Council Victoria, grid.3263.4
  4. (4) University of Cambridge, grid.5335.0
  5. (5) FIRC Institute of Molecular Oncology, grid.7678.e
  6. (6) Catalan Institute of Oncology, grid.418701.b
  7. (7) Hospital Clínico San Carlos, grid.411068.a
  8. (8) University of Valladolid, grid.5239.d
  9. (9) Hospital Universitari Vall d'Hebron, grid.411083.f
  10. (10) Hospital de Sant Pau, grid.413396.a
  11. (11) Molecular Diagnostics Laboratory IRRP, National Centre for Scientific Research Demokritos Aghia Paraskevi Attikis, Athens, Greece
  12. (12) Molecular Genetics Laboratory (Department of Biochemistry), Cruces Hospital Barakaldo, Bizkaia, Spain
  13. (13) Hospital Clínico Universitario Lozano Blesa, grid.411050.1
  14. (14) Centre Hospitalier Universitaire de Québec, grid.411081.d
  15. (15) Lund University, grid.4514.4
  16. (16) Karolinska University Hospital, grid.24381.3c
  17. (17) Skåne University Hospital, grid.411843.b
  18. (18) University of Chicago Medical Center, grid.412578.d
  19. (19) University of California, San Francisco, grid.266102.1
  20. (20) University of Pennsylvania, grid.25879.31
  21. (21) The University of Texas MD Anderson Cancer Center, grid.240145.6
  22. (22) Cedars-Sinai Medical Center, grid.50956.3f
  23. (23) Cancer Prevention Institute of California, grid.280669.3
  24. (24) Stanford University, grid.168010.e
  25. (25) Temple University Health System, grid.412530.1
  26. (26) University of Melbourne, grid.1008.9
  27. (27) Columbia University, grid.21729.3f
  28. (28) University of Utah, grid.223827.e
  29. (29) Vilnius University Hospital Santariskiu Klinikos, grid.426597.b
  30. (30) University of Pretoria, grid.49697.35
  31. (31) City Of Hope National Medical Center, grid.410425.6
  32. (32) Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  33. (33) Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  34. (34) Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  35. (35) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  36. (36) European Institute of Oncology, grid.15667.33
  37. (37) Centro di Riferimento Oncologico, grid.418321.d
  38. (38) Ospedale San Martino, grid.410345.7
  39. (39) University of Florence, grid.8404.8
  40. (40) Sapienza University of Rome, grid.7841.a
  41. (41) University of Insubria, grid.18147.3b
  42. (42) Dana-Farber Cancer Institute, grid.65499.37
  43. (43) Manchester University NHS Foundation Trust, grid.498924.a
  44. (44) Guy's Hospital, grid.239826.4
  45. (45) Royal Marsden NHS Foundation Trust, grid.5072.0
  46. (46) Yorkshire Regional Genetics Service, Leeds, United Kingdom
  47. (47) Royal Hospital for Sick Children, grid.415571.3
  48. (48) West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, United Kingdom
  49. (49) Princess Anne Hospital, grid.415216.5
  50. (50) Sheffield Children's Hospital, grid.413991.7
  51. (51) University College London, grid.83440.3b
  52. (52) Royal Devon and Exeter Hospital, grid.416118.b
  53. (53) Addenbrooke's Hospital, grid.120073.7
  54. (54) Institute of Human Genetics, Centre for Life, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom
  55. (55) Western General Hospital, grid.417068.c
  56. (56) Great Ormond Street Hospital for Children NHS Foundation Trust, grid.424537.3
  57. (57) Churchill Hospital, grid.415719.f
  58. (58) Belfast City Hospital, grid.412914.b
  59. (59) South West Regional Genetics Service, Bristol, United Kingdom
  60. (60) St. James's Hospital, grid.416409.e
  61. (61) Liverpool Womens NHS Foundation Trust, grid.419317.9
  62. (62) University of Kansas Medical Center, grid.412016.0
  63. (63) University Hospital Cologne, grid.411097.a
  64. (64) Leipzig University, grid.9647.c
  65. (65) Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
  66. (66) University Hospital Schleswig-Holstein, grid.412468.d
  67. (67) Department of Gynaecology and Obstetrics, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
  68. (68) University Hospital Heidelberg, grid.5253.1
  69. (69) University Hospital Ulm, grid.410712.1
  70. (70) Hannover Medical School, grid.10423.34
  71. (71) University of Münster, grid.5949.1
  72. (72) Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany
  73. (73) Charité, grid.6363.0
  74. (74) University of Würzburg, grid.8379.5
  75. (75) Institute Curie, grid.418596.7
  76. (76) Paris Descartes University, grid.10992.33
  77. (77) Centre Léon Bérard, grid.418116.b
  78. (78) Cancer Center of Lyon, grid.462282.8
  79. (79) Ghent University, grid.5342.0
  80. (80) Roswell Park Cancer Institute, grid.240614.5
  81. (81) Prince of Wales Hospital, grid.415193.b
  82. (82) The Ohio State University, grid.261331.4
  83. (83) NorthShore University HealthSystem, grid.240372.0
  84. (84) Tufts Medical Center, grid.67033.31
  85. (85) Yale University, grid.47100.32
  86. (86) Helsinki University Central Hospital, grid.15485.3d
  87. (87) Antoni van Leeuwenhoek Hospital, grid.430814.a
  88. (88) Academic Medical Center, grid.5650.6
  89. (89) VU University Medical Center, grid.16872.3a
  90. (90) University Medical Center Groningen, grid.4494.d
  91. (91) Leiden University Medical Center, grid.10419.3d
  92. (92) Maastricht University Medical Centre, grid.412966.e
  93. (93) Radboud University Nijmegen Medical Centre, grid.10417.33
  94. (94) Erasmus University Medical Center, grid.5645.2
  95. (95) University Medical Center Utrecht, grid.7692.a
  96. (96) National Institute of Oncology, grid.419617.c
  97. (97) Pomeranian Medical University, grid.107950.a
  98. (98) Medical University of Warsaw, grid.13339.3b
  99. (99) Department of Oncology, Landspitali University Hospital and BMC, Faculty of Medicine, University of Iceland, Reykjavik Iceland
  100. (100) Hôpitaux Universitaires de Strasbourg, grid.412220.7
  101. (101) Istituto Oncologico Veneto, grid.419546.b
  102. (102) Portuguese Oncology Institute, grid.418711.a
  103. (103) QIMR Berghofer Medical Research Institute, grid.1049.c
  104. (104) Peter MacCallum Cancer Centre, grid.1055.1
  105. (105) Mayo Clinic, grid.66875.3a
  106. (106) Mayo Clinic, grid.417468.8
  107. (107) University of Delaware, grid.33489.35
  108. (108) Memorial Sloan Kettering Cancer Center, grid.51462.34
  109. (109) Medical University of Vienna, grid.22937.3d
  110. (110) Moffitt Cancer Center, grid.468198.a
  111. (111) National Cancer Institute, grid.48336.3a
  112. (112) Clalit National Israeli Cancer Control Center, Haifa, Israel
  113. (113) Lunenfeld-Tanenbaum Research Institute, grid.250674.2
  114. (114) University of Toronto, grid.17063.33
  115. (115) University Health Network, grid.231844.8
  116. (116) Mount Sinai Hospital, grid.416166.2
  117. (117) Vejle Sygehus, grid.417271.6, Southern Denmark Region
  118. (118) Aalborg Hospital, grid.27530.33, North Denmark Region
  119. (119) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  120. (120) Odense University Hospital, grid.7143.1, Southern Denmark Region
  121. (121) Sheba Medical Center, grid.413795.d

Description

Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.

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Times Cited: 27

Field Citation Ratio (FCR): 3.09

Relative Citation ratio (RCR): 1.11

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