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Association of breast cancer risk loci with breast cancer survival.

About this Publication
Title
Association of breast cancer risk loci with breast cancer survival.
Pubmed ID
25611573 (View this publication on the PubMed website)
Publication
Int. J. Cancer. 2015 Dec; Volume 137 (Issue 12): Pages 2837-45
Authors
Barrdahl M, Canzian F, Lindström S, Shui I, Black A, Hoover RN, Ziegler RG, Buring JE, Chanock SJ, Diver WR, Gapstur SM, Gaudet MM, Giles GG, Haiman C, Henderson BE, Hankinson S, Hunter DJ, Joshi AD, Kraft P, Lee IM, ...show more Le Marchand L, Milne RL, Southey MC, Willett W, Gunter M, Panico S, Sund M, Weiderpass E, Sánchez MJ, Overvad K, Dossus L, Peeters PH, Khaw KT, Trichopoulos D, Kaaks R, Campa D
Affiliations
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, MA.
  • Department of Epidemiology, Harvard School of Public Health, Boston, MA.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
  • Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, MA.
  • Epidemiology Research Program, American Cancer Society, NW Atlanta, GA.
  • Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia.
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI.
...show more
  • Department of Pathology, University of Melbourne, VIC, Australia.
  • Department of Nutrition, Harvard School of Public Health, Boston, MA.
  • Department of Epidemiology Biostatistics, School of Public Health, Imperial College, South Kensington Campus, London, United Kingdom.
  • Dipartimento Di Medicina Clinica E Chirurgia, Naples, Italy.
  • Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Sweden.
  • Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Norway.
  • Escuela Andaluza De Salud Pública, Instituto De Investigación Biosanitaria Ibs, Granada, Hospitales Universitarios De Granada/Universidad De Granada, Spain.
  • Department of Public Health, Section for Epidemiology, Aarhus University, Denmark.
  • INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, Villejuif, France.
  • Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.
  • Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, United Kingdom.
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.

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