Article open access publication

Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

PLoS ONE, Public Library of Science (PLoS), ISSN 1932-6203

Volume 10, 6, 2015

DOI:10.1371/journal.pone.0128106, Dimensions: pub.1006753997, PMC: PMC4474865, PMID: 26091520,

Authors

Aben, Katja K H (5) (6)
Bjorge, Line (14) (15)
Campbell, Ian G (22) (23)
Carty, Karen (24) (25)
du Bois, Andreas (32) (33)
Dicks, Ed (2)
Fasching, Peter A. (12) (41)
Giles, Graham G (9) (23)
Harter, Philipp (32) (33)
Heitz, Florian (32) (33)
Hogdall, Estrid (48) (49)
Krakstad, Camilla (14) (15)
Kjaer, Susanne K. (49) (52)
Le, Nhu D. (19)
Lu, Karen (46)
Pike, Malcolm C (3) (13)
Poole, Elizabeth M (28) (64)
Salvesen, Helga B. (14) (15)
Schernhammer, Eva (28) (64)
Teo, Soo-Hwang (70) (71)
Tangen, Ingvild L. (14) (15)
Wu, Xifeng (46)
Zheng, Wei (68)

* Corresponding author

Affiliations

Organisations

  1. (1) Moffitt Cancer Center, grid.468198.a
  2. (2) University of Cambridge, grid.5335.0
  3. (3) University of Southern California, grid.42505.36
  4. (4) Johns Hopkins All Children's Hospital, grid.413611.0
  5. (5) Comprehensive Cancer Center The Netherlands, Nijmegen, The Netherlands
  6. (6) Radboud University Nijmegen Medical Centre, grid.10417.33
  7. (7) University of California, Irvine, grid.266093.8
  8. (8) N.N. Alexandrov National Cancer Centre, grid.477553.7
  9. (9) Cancer Council Victoria, grid.3263.4
  10. (10) Rutgers, The State University of New Jersey, grid.430387.b
  11. (11) Oregon Health & Science University, grid.5288.7
  12. (12) Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nuremberg Comprehensive Cancer Center, Erlangen EMN, Erlangen, Germany
  13. (13) Memorial Sloan Kettering Cancer Center, grid.51462.34
  14. (14) Haukeland University Hospital, grid.412008.f
  15. (15) University of Bergen, grid.7914.b
  16. (16) Hannover Medical School, grid.10423.34
  17. (17) National Cancer Institute, grid.48336.3a
  18. (18) Simon Fraser University, grid.61971.38
  19. (19) BC Cancer Agency, grid.248762.d
  20. (20) University of Pittsburgh, grid.21925.3d
  21. (21) Helsinki University Central Hospital, grid.15485.3d
  22. (22) Peter MacCallum Cancer Centre, grid.1055.1
  23. (23) University of Melbourne, grid.1008.9
  24. (24) Glasgow Royal Infirmary, grid.411714.6
  25. (25) Beatson West of Scotland Cancer Centre, grid.422301.6
  26. (26) German Cancer Research Center, grid.7497.d
  27. (27) University of New Mexico, grid.266832.b
  28. (28) Harvard University, grid.38142.3c
  29. (29) Mayo Clinic, grid.66875.3a
  30. (30) Pomeranian Medical University, grid.107950.a
  31. (31) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
  32. (32) Department of Gynaecology and Gynaecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany
  33. (33) Department of Gynaecology and Gynaecologic Oncology, Kliniken Essen-Mitte/ Evang. Huyssens-Stiftung/ Knappschaft GmbH, Essen, Germany
  34. (34) Universitair Ziekenhuis Leuven, grid.410569.f
  35. (35) Department of Epidemiology, The Geisel School of Medicine Hanover, New Hampshire, United States of America
  36. (36) Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington, United States of America
  37. (37) Department of Gynecology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
  38. (38) University of Southampton, grid.5491.9
  39. (39) University of Pittsburgh Cancer Institute, grid.478063.e
  40. (40) University of Erlangen-Nuremberg, grid.5330.5
  41. (41) University of California, Los Angeles, grid.19006.3e
  42. (42) University of Kansas Medical Center, grid.412016.0
  43. (43) Shanghai Cancer Institute, grid.419087.3
  44. (44) University College London, grid.83440.3b
  45. (45) Cedars-Sinai Medical Center, grid.50956.3f
  46. (46) The University of Texas MD Anderson Cancer Center, grid.240145.6
  47. (47) The Juliane Marie Centre, Department of Gynecology, Righospitalet, University of Copenhagen, Copenhagen, Denmark
  48. (48) University of Copenhagen, grid.5254.6, KU
  49. (49) Danish Cancer Society, grid.417390.8
  50. (50) Kyushu University, grid.177174.3
  51. (51) Medical University of South Carolina, grid.259828.c
  52. (52) Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  53. (53) Flanders Institute for Biotechnology, grid.11486.3a
  54. (54) KU Leuven, grid.5596.f
  55. (55) Roswell Park Cancer Institute, grid.240614.5
  56. (56) Texas Southern University, grid.264771.1
  57. (57) Department of Obstetrics and Gynaecology, University Malaya Medical Centre, University Malaya, Kuala Lumpur, Malaysia
  58. (58) Stanford University, grid.168010.e
  59. (59) Public Health Ontario, grid.415400.4
  60. (60) University of Glasgow, grid.8756.c
  61. (61) The University of Texas Health Science Center at Houston, grid.267308.8
  62. (62) Duke University Hospital, grid.189509.c
  63. (63) University of Michigan, grid.214458.e
  64. (64) Brigham and Women's Hospital, grid.62560.37
  65. (65) Yale University, grid.47100.32
  66. (66) University of Toronto, grid.17063.33
  67. (67) Institut für Humangenetik, Wiesbaden, Germany
  68. (68) Vanderbilt University, grid.152326.1
  69. (69) University of Hawaii at Manoa, grid.410445.0
  70. (70) University Malaya Cancer Research Institute, University Malaya Medical Centre, University Malaya, Kuala Lumpur, Maylaysia
  71. (71) Cancer Research Initiatives Foundation, grid.427737.2
  72. (72) Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  73. (73) Duke University, grid.26009.3d

Description

BACKGROUND: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. METHODS: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. RESULTS: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4). CONCLUSION: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.

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Times Cited: 12

Field Citation Ratio (FCR): 2.06

Relative Citation ratio (RCR): 0.41

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