Article open access publication

Association of breast cancer risk loci with breast cancer survival

International Journal of Cancer, Wiley, ISSN 0020-7136

Volume 137, 12, 2015

DOI:10.1002/ijc.29446, Dimensions: pub.1036381959, PMC: PMC4615576, PMID: 25611573,

Affiliations

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  1. (1) German Cancer Research Center, grid.7497.d
  2. (2) Harvard University, grid.38142.3c
  3. (3) National Cancer Institute, grid.48336.3a
  4. (4) Brigham and Women's Hospital, grid.62560.37
  5. (5) Frederick National Laboratory for Cancer Research, grid.418021.e
  6. (6) American Cancer Society, grid.422418.9
  7. (7) Cancer Council Victoria, grid.3263.4
  8. (8) University of Melbourne, grid.1008.9
  9. (9) University of Southern California, grid.42505.36
  10. (10) University of Massachusetts Amherst, grid.266683.f
  11. (11) University of Hawaii at Manoa, grid.410445.0
  12. (12) Imperial College London, grid.7445.2
  13. (13) Dipartimento Di Medicina Clinica E Chirurgia, Naples, Italy.
  14. (14) Umeå University, grid.12650.30
  15. (15) Cancer Registry of Norway, grid.418941.1
  16. (16) Folkhälsans Forskningscentrum, grid.428673.c
  17. (17) Karolinska Institute, grid.4714.6
  18. (18) The Arctic University of Norway, grid.10919.30
  19. (19) Andalusian School of Public Health, grid.413740.5
  20. (20) Institute of Health Carlos III, grid.413448.e
  21. (21) Aarhus University, grid.7048.b, AU
  22. (22) Centre for research in epidemiology and population health, grid.463845.8
  23. (23) Institut Gustave Roussy, grid.14925.3b
  24. (24) University of Paris-Sud, grid.5842.b
  25. (25) University Medical Center Utrecht, grid.7692.a
  26. (26) University of Cambridge, grid.5335.0
  27. (27) Academy of Athens, grid.417593.d
  28. (28) Hellenic Health Foundation, grid.424637.0

Description

The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele =0.70; 95% CI: 0.58-0.85; ptrend  = 2.84 × 10(-4) ; HRheterozygotes  = 0.71; 95% CI: 0.55-0.92; HRhomozygotes  = 0.48; 95% CI: 0.31-0.76; p2DF  = 1.45 × 10(-3) ). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; ptrend  = 6.6 × 10(-4) ; HRheterozygotes  = 0.96 95% CI: 0.90-1.03; HRhomozygotes  = 1.21; 95% CI: 1.09-1.35; p2DF =1.25 × 10(-4) ). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662.

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Aarhus University

Danish Open Access Indicator

2015: Unused

Research area: Medicine

Danish Bibliometrics Indicator

2015: Level 1

Research area: Medicine

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Times Cited: 20

Field Citation Ratio (FCR): 5.45

Relative Citation ratio (RCR): 0.83

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