Additional prognostic value of polymorphisms within the 3'-untranslated region of programmed cell death pathway genes in early-stage breast cancer.

Abstract

The programmedcell death (PCD) pathway plays an important role in restricting cancer cell survival and proliferation. However, limited studies have investigated the association between genetic variants in the 3'-untranslated region of the PCD pathway genes and breast cancer outcomes. In this study, we genotyped 28 potentially functional single nucleotide polymorphisms (SNPs)in 23 PCD pathwaygenesin 1,177patients withearly-stagebreast cancer(EBC)from a Han Chinese population.The median follow-up period was 174 months. Among all the candidateSNPs, fourindependent SNPs (rs4900321 and rs7150025 in ATG2B, rs6753785 in BCL2L11, and rs2213181 in c-Kit) were associated with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer-specific survival (BCSS)and overall survival (OS), respectively. Further combined genotypes of these four SNPs revealed that the survival decreasedas the number of unfavorable genotypes increased(Ptrend= 1.0 × 10-6, 8.5 × 10-8, 3.6 × 10-4, and 1.3 × 10-4for iDFS, DDFS, BCSS, and OS, respectively). Receiver operating characteristiccurve analysis demonstrated that incorporating unfavorable genotypes and clinicopathological variables improved the ability to predict EBC survival (P= 0.006, 0.004, 0.029, and 0.019 for iDFS, DDFS, BCSS, and OS, respectively).Additionally, rs6753785 and rs2213181 were associated with BCL2L11and c-KitmRNA expression, respectively. Our results suggest that these four SNPs may act as novel biomarkers for EBC survival, possibly by modulating the expression of the corresponding genes.