Common germline polymorphisms associated with breast cancer-specific survival

Abstract

IntroductionPrevious studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium.MethodsA literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect.ResultsFifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease.ConclusionsAlthough no variants reached genome-wide significance (P <5 x 10−8), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between common variants and prognosis, at more stringent significance levels.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0570-7) contains supplementary material, which is available to authorized users.

Genome‐wide association study identifies the GLDC/IL33 locus associated with survival of osteosarcoma patients

“…Linkage disequilibrium (LD) was evaluated with r 2 based on the 1000 Genomes Project (Phase 3 genotype data) 45 using LDlink (http://analysistools.nci.nih.gov/LDlink/). 23 Chromosome location for human genome assembly hg19 was retrieved from the National Center for Biotechnology Information's (NCBI) Gene database (http://www.ncbi.nlm.nih.gov/gene/). Genomic annotation of SNP markers was conducted using the Encyclopedia of DNA Elements (ENCODE) 50 tool HaploReg 51 and RegulomeDB 52 for all cell lines.…”

Assessment of the prognostic role of a 94-single nucleotide polymorphisms risk score in early breast cancer in the SIGNAL/PHARE prospective cohort: no correlation with clinico-pathological characteristics and outcomes

“…) [35]. Preliminary analyses in our GWAS study do not indicate that this variant is associated with outcomes (unpublished data).…”

“…From these 62 variants, only one (rs2981582, in FGFR2 on chromosome 10) is used in our 94-SNP score. It has been identified as possibly associated with outcomes in breast cancer, with a HR (90% CI) of 1.09 (1.04-1.14) [35]. This variant reached nominal significance (p < 0.05) but did not reach genome-wide significance (p < 5 × 10…”

“…They have identified SNPs that may influence breast cancer prognosis [28,[32][33][34]. Around 60 variants have been described to date as potentially correlated with breast cancer outcomes [35]. Most of them are involved in pathways playing fundamental roles in oncogenesis such as cell cycle control, cell adhesion or DNA repair [35,36].…”

“…However, in a cohort of over 37,000 patients with breast cancer, none of the 62 studied variants showed significant association with outcomes [35,[37][38][39][40][41][42]. From these 62 variants, only one (rs2981582, in FGFR2 on chromosome 10) is used in our 94-SNP score.…”