Article open access publication

Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study

Breast Cancer Research, Springer Nature, ISSN 1465-5411

Volume 16, 3, 2014

DOI:10.1186/bcr3662, Dimensions: pub.1043714368, PMC: PMC4522594, PMID: 24887515,

Authors

Orr, Nick (1)
Burwinkel, Barbara (14) (15)
Sohn, Christof (14) (16)
Guénel, Pascal (17) (18)
Truong, Therese (17) (18)
Cordina, Emilie (17) (18)
Menegaux, Florence (17) (18)
Benitez, Javier (20) (23)
Brauch, Hiltrud (30) (31)
Mannermaa, Arto (39) (40)
Kataja, Vesa (39) (40)
Kosma, Veli-Matti (39) (40)
Wu, Anna H (42)
Smeets, Dominiek (43) (44)
Peterlongo, Paolo (47) (48)
Pensotti, Valeria (48) (49)
Giles, Graham G (4) (51)
Severi, Gianluca (4) (51)
Baglietto, Laura (4) (51)
Teo, Soo (55) (56)
Phuah, Sze Yee (55) (56)
Zheng, Wei (60)
Andrulis, Irene L (64) (65)
Knight, Julia A (64) (65)
Glendon, Gord (64) (66)
Hall, Per (38)
Cox, Angie (73)
Blot, William (60) (74)
Signorello, Lisa B (75) (76) (77)
Hartman, Mikael (80) (81)
Miao, Hui (76) (77)
Lim, Wei Yen (80) (81)
Försti, Asta (15) (82)
Shen, Chen-Yang (91) (92)
Wang, Jean (78)

* Corresponding author

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  1. (1) Institute of Cancer Research, grid.18886.3f
  2. (2) London School of Hygiene & Tropical Medicine, grid.8991.9
  3. (3) Royal Marsden Hospital, grid.424926.f
  4. (4) University of Melbourne, grid.1008.9
  5. (5) Antoni van Leeuwenhoek Hospital, grid.430814.a
  6. (6) Radboud University Nijmegen, grid.5590.9
  7. (7) University of Warwick, grid.7372.1
  8. (8) University of California, Los Angeles, grid.19006.3e
  9. (9) University Hospital Erlangen, grid.411668.c
  10. (10) University of Erlangen-Nuremberg, grid.5330.5
  11. (11) Guy's Hospital, grid.239826.4
  12. (12) University of Oxford, grid.4991.5
  13. (13) Surgery, Clinical Science Institute, Galway University Hospital and National University of Ireland, University Road, Galway, Ireland
  14. (14) Heidelberg University, grid.7700.0
  15. (15) German Cancer Research Center, grid.7497.d
  16. (16) National Center for Tumor Diseases, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
  17. (17) French Institute of Health and Medical Research, grid.7429.8
  18. (18) University of Paris-Sud, grid.5842.b
  19. (19) Herlev Hospital, grid.411900.d, Capital Region
  20. (20) Spanish National Cancer Research Centre, grid.7719.8
  21. (21) Hospital Universitario La Paz, grid.81821.32
  22. (22) Hospital Monte Naranco, grid.414858.4
  23. (23) Centre for Biomedical Network Research on Rare Diseases, grid.452372.5
  24. (24) City Of Hope National Medical Center, grid.410425.6
  25. (25) University of California, Irvine, grid.266093.8
  26. (26) Cancer Prevention Institute of California, grid.280669.3
  27. (27) Clinic of Gynecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, D-81675, Munich, Germany
  28. (28) Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, 69121, Heidelberg, Germany
  29. (29) University Hospital Cologne, grid.411097.a
  30. (30) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
  31. (31) University of Tübingen, grid.10392.39
  32. (32) Department of Internal Medicine, Evangelische Kliniken Bonn GGmbH, Johanniter Krankenhaus, 53113, Bonn, Germany
  33. (33) Department of Obstetrics and Gynecology, Helsinki University Central Hospital, University of Helsinki, Haartmaninkatu 2, P.O. Box 140, FIN-00029, Helsinki, Finland
  34. (34) Helsinki University Central Hospital, grid.15485.3d
  35. (35) Aichi Cancer Center, grid.410800.d
  36. (36) Hannover Medical School, grid.10423.34
  37. (37) N.N. Alexandrov Research Institute of Oncology and Medical Radiology, 223040, p. Lesnoy, Minsk, Belarus
  38. (38) Karolinska Institute, grid.4714.6
  39. (39) Kuopio University Hospital, grid.410705.7
  40. (40) University of Eastern Finland, grid.9668.1
  41. (41) QIMR Berghofer Medical Research Institute, grid.1049.c
  42. (42) University of Southern California, grid.42505.36
  43. (43) Flanders Institute for Biotechnology, grid.11486.3a
  44. (44) KU Leuven, grid.5596.f
  45. (45) Universitair Ziekenhuis Leuven, grid.410569.f
  46. (46) University Medical Center Hamburg-Eppendorf, grid.13648.38
  47. (47) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  48. (48) FIRC Institute of Molecular Oncology, grid.7678.e
  49. (49) European Institute of Oncology, grid.15667.33
  50. (50) Mayo Clinic, grid.66875.3a
  51. (51) Cancer Council Victoria, grid.3263.4
  52. (52) Royal Victoria Hospital, grid.416229.a
  53. (53) University of Montreal, grid.14848.31
  54. (54) Centre Hospitalier Universitaire de Québec, grid.411081.d
  55. (55) University of Malaya, grid.10347.31
  56. (56) Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, 1, Jalan SS 12 / 1A, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia
  57. (57) Singapore Eye Research Institute, National University of Singapore, Singapore National Eye Centre, 11 Third Hospital Avenue, 168751, Singapore, Singapore
  58. (58) Faculty of Medicine (Faculty Division Ahus), University of Oslo, Sogn Arena, Klaus Torgårds vei 3, 2. etg, 0372, Oslo, Norway
  59. (59) Oslo University Hospital, grid.55325.34
  60. (60) Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 1161 21st Ave S # T1217, 37232, Nashville, TN, USA
  61. (61) Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, Oulu University Hospital, Kajaanintie 50, 90220, Oulu, Finland
  62. (62) Department of Oncology, Oulu University Hospital, University of Oulu, Kajaanintie 50, 90220, Oulu, Finland
  63. (63) Department of Surgery, Oulu University Hospital, University of Oulu, Kajaanintie 50, 90220, Oulu, Finland
  64. (64) Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 982 - 600 University Avenue, M5G 1X5, Toronto, Ontario, Canada
  65. (65) University of Toronto, grid.17063.33
  66. (66) Ontario Cancer Genetics Network, 620 University Avenue, M5G 2L7, Toronto, Ontario, Canada
  67. (67) University Health Network, grid.231844.8
  68. (68) Leiden University Medical Center, grid.10419.3d
  69. (69) National Cancer Institute, grid.48336.3a
  70. (70) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
  71. (71) Erasmus University Medical Center, grid.5645.2
  72. (72) Genome Institute of Singapore, grid.418377.e
  73. (73) University of Sheffield, grid.11835.3e
  74. (74) International Epidemiology Institute, grid.419344.f
  75. (75) Dana-Farber/Harvard Cancer Center, grid.477947.e
  76. (76) Channing Division of Network Medicine, Harvard Medical School, 181 Longwood Avenue, 02115, Boston, MA, USA
  77. (77) Harvard University, grid.38142.3c
  78. (78) University of Cambridge, grid.5335.0
  79. (79) Seoul National University, grid.31501.36
  80. (80) National University of Singapore, grid.4280.e
  81. (81) National University Health System, grid.410759.e
  82. (82) Lund University, grid.4514.4
  83. (83) Charité, grid.6363.0
  84. (84) Frauenklinik der Stadtklinik Baden-Baden, Balger Strasse 50, 76532, Baden-Württemberg, Germany
  85. (85) Pomeranian Medical University, grid.107950.a
  86. (86) Medical University of Warsaw, grid.13339.3b
  87. (87) National Cancer Institute of Thailand, grid.419173.9
  88. (88) International Agency For Research On Cancer, grid.17703.32
  89. (89) The Ohio State University, grid.261331.4
  90. (90) National Centre of Scientific Research Demokritos, grid.6083.d
  91. (91) China Medical University, grid.254145.3
  92. (92) Institute of Biomedical Sciences, Academia Sinica, grid.482251.8
  93. (93) Tri-Service General Hospital, grid.278244.f
  94. (94) National Taiwan University Hospital, grid.412094.a
  95. (95) Kaohsiung Medical University Chung-Ho Memorial Hospital, grid.412027.2
  96. (96) McGill University and Génome Québec Innovation Centre, grid.411640.6

Description

INTRODUCTION: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years. METHODS: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. RESULTS: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P(trend) = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P(het) = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR(het) = 0.84, 95% CI 0.75, 0.94; OR(hom) = 0.81, 95% CI 0.51, 1.30; P(trend) = 0.002) but not for those who had their menarche age ≤11 years (OR(het) = 1.06, 95% CI 0.95, 1.19, OR(hom) = 1.07, 95% CI 0.67, 1.72; P(trend) = 0.29). CONCLUSIONS: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.

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Times Cited: 8

Field Citation Ratio (FCR): 1.8

Relative Citation ratio (RCR): 0.32

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