Year: 2015
Type: article
Study design: Observational Study
Abstract: 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.
Source: International Journal of Cancer
DOI: 10.1002/ijc.29446
Authors: Myrto Barrdahl, Federico Canzian, Sara Lindström, Irene Shui, Amanda Black, Robert N. Hoover, Regina G. Ziegler, Julie E. Buring, Stephen J. Chanock, W. Ryan Diver, Susan M. Gapstur, Mia M. Gaudet, Graham G. Giles, Christopher Haiman, Brian E. Henderson, Susan Hankinson, David J. Hunter, Amit D. Joshi, Peter Kraft, I‐Min Lee, Loic Le Marchand, Roger L. Milne, Melissa C. Southey, Walter Willett, Marc Gunter, Salvatore Panico, Malin Sund, Elisabete Weiderpass, María‐José Sánchez, Kim Overvad, Laure Dossus, Petra H Peeters, Kay‐Tee Khaw, Dimitrios Trichopoulos, Rudolf Kaaks, Daniele Campa
Institutions: German Cancer Research Center, Harvard University, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Brigham and Women's Hospital, Frederick National Laboratory for Cancer Research, American Cancer Society, The University of Melbourne, Cancer Council Victoria, University of Southern California, University of Massachusetts Amherst, University of Hawaiʻi at Mānoa, University of Hawaii System, Imperial College London, Federico II University Hospital, Umeå University, Karolinska Institutet, Cancer Registry of Norway, Folkhälsans Forskningscentrum, UiT The Arctic University of Norway, Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Andalusian School of Public Health, Aarhus University, Université Paris-Sud, Inserm, Centre de recherche en Epidémiologie et Santé des Populations, Utrecht University, University Medical Center Utrecht, MRC Centre for Environment and Health, University of Cambridge, Academy of Athens, Hellenic Health Foundation
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Awards: G1364610698, G1420790711, G2036036603, G2919159421, G3276551827, G3771853605, G4450071017, Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3, G5021959070, G5432062437, G5897142711, NIHR Senior Investigator Award, Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3, G8013581208, G814381192, University of Hawaii Cancer Center CCSG
OpenAlex ID: W2149998987