Association of breast cancer risk loci with breast cancer survival.

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.

• 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
• Journal: International journal of cancer (Int J Cancer) Vol. 137 Issue 12 Pg. 2837-45 (Dec 15 2015) ISSN: 1097-0215 [Electronic] United States
• PMID: 25611573 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2015 UICC.

Topics

• Breast Neoplasms (genetics, mortality)
• Female
• Genetic Association Studies
• Genetic Loci
• Genetic Predisposition to Disease
• Humans
• Polymorphism, Single Nucleotide
• Proportional Hazards Models
• Risk Factors