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Int J Cancer. 2015 Dec 15;137(12):2837-45. doi: 10.1002/ijc.29446. Epub 2015 Aug 14.

Association of breast cancer risk loci with breast cancer survival.

Author information

1
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
2
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
3
Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, MA.
4
Department of Epidemiology, Harvard School of Public Health, Boston, MA.
5
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
6
Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, MA.
7
Divisions of Preventive Medicine and Aging, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
8
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
9
Core Genotyping Facility Frederick National Laboratory for Cancer Research, Gaithersburg, MD.
10
Epidemiology Research Program, American Cancer Society, NW Atlanta, GA.
11
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia.
12
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, VIC, Australia.
13
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
14
Department of Epidemiology, University of Massachusetts-Amherst School of Public Health and Health Sciences, Amherst, MA.
15
Cancer Research Center, Brigham and Women's Hospital, Boston, MA.
16
Department of Medicine, Harvard Medical School, Boston, MA.
17
Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI.
18
Department of Pathology, University of Melbourne, VIC, Australia.
19
Department of Nutrition, Harvard School of Public Health, Boston, MA.
20
Department of Epidemiology Biostatistics, School of Public Health, Imperial College, South Kensington Campus, London, United Kingdom.
21
Dipartimento Di Medicina Clinica E Chirurgia, Naples, Italy.
22
Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Sweden.
23
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Norway.
24
Department of Research, Cancer Registry of Norway, Oslo, Norway.
25
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
26
Samfundet Folkhälsan, Helsinki, Finland.
27
Escuela Andaluza De Salud Pública, Instituto De Investigación Biosanitaria Ibs, Granada, Hospitales Universitarios De Granada/Universidad De Granada, Spain.
28
CIBER De Epidemiología Y Salud Pública (CIBERESP), Barcelona, Spain.
29
Department of Public Health, Section for Epidemiology, Aarhus University, Denmark.
30
INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, Villejuif, France.
31
University of Paris Sud, UMRS 1018, Villejuif, France.
32
IGR, Villejuif, France.
33
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.
34
MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
35
Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, United Kingdom.
36
Bureau of Epidemiologic Research, Academy of Athens, Greece.
37
Hellenic Health Foundation, Athens, Greece.

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.

KEYWORDS:

BPC3; SNP; breast cancer; meta-analysis; survival

PMID:
25611573
PMCID:
PMC4615576
DOI:
10.1002/ijc.29446
[Indexed for MEDLINE]
Free PMC Article

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