Association of breast cancer risk loci with breast cancer survival

作者：Barrdahl Myrto; Canzian Federico; Lindstroem Sara; Shui Irene; Black Amanda; Hoover Robert N; Ziegler Regina G; Buring Julie E; Chanock Stephen J; Diver W Ryan; Gapstur Susan M; Gaudet Mia M; Giles Graham G; Haiman Christopher; Henderson Brian E; Hankinson Susan; Hunter David J; Joshi Amit D; Kraft Peter; Lee I Min; Le Marchand Loic; Milne Roger L; Southey Melissa C; Willett Walter; Gunter Marc; Panico Salvatore; Sund Malin; Weiderpass Elisabete

来源：International Journal of Cancer, 2015, 137(12): 2837-2845.

DOI：10.1002/ijc.29446

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

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; p(trend)=2.84 x 10(-4); HRheterozygotes=0.71; 95% CI: 0.55-0.92; HRhomozygotes=0.48; 95% CI: 0.31-0.76; p(2DF)=1.45 x 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; p(trend)=6.6 x 10(-4); HRheterozygotes=0.96 95% CI: 0.90-1.03; HRhomozygotes=1.21; 95% CI: 1.09-1.35; p(2DF)=1.25 x 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.
What's new? Genetic factors are known to influence the risk of breast cancer, but inherited genetic variation may also affect disease prognosis and response to treatment. In this study, the we investigated whether single nucleotide polymorphisms (SNPs) that are known to be associated with breast cancer risk might also influence the survival of breast-cancer patients. While two of the investigated SNPs may influence survival, there was otherwise no indication that SNP alleles related to breast cancer risk also play a role in the survival of breast cancer patients.

• 出版日期2015-12-15