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DOI: 10.1055/s-0034-1388571
Genetic breast cancer susceptibility variants and prognosis in the prospectively randomized SUCCESS A trial
Large scale genotyping studies have identified more than 70 single nucleotide polymorphisms (SNPs) that are associated with breast cancer (BC) risk. The knowledge about risk factors that are associated with prognosis is however growing much slower. Aim of this study was therefore to investigate nine known breast cancer risk SNPs for their prognostic relevance.
Breast cancer risk SNPs rs17468277(CASP8), rs2981582(FGFR2), rs13281615(8q24), rs3817198(LSP1), rs889312(MAP3K1), rs3803662(TOX3), rs13387042(2q35), rs4973768(SLC4A7) rs6504950(COX11) of 1,687 BC patients from a random sample from the SUCCESS A study were genotyped. Cox proportional hazards models were used to test the association of these SNPs with overall survival (OS) and disease free survival (DFS). Additional analyses were carried out for molecular subgroups.
The median follow-up time was 59 months for OS and 58 months for DFS. When comparing the genetic survival model with the clinical survival model rs3817198 was the only SNP that significantly influenced DFS and OS (likelihood ratio test, corrected p < 0.001 and p = 0.01). In particular this effect was limited to patients with triple negative tumors, where patients with two minor alleles had significantly improved OS [HR 0.03; 95% CI (0.00, 0.28)] and DFS [HR 0.09; 95% CI (0.02, 0.36)] compared to patients with two common alleles.
We showed that the intron variant rs3817198 in LSP1 (encoding lymphocyte-specific protein 1) has a prognostic relevance, especially in this subgroup of triple negative patients treated with anthracycline and taxane based chemotherapy. Further studies are needed to confirm this most likely pharmacogenetic effect and to identify the underlining mechanism.