Abstract 2607: Genetic variants in the vitamin D pathway and breast cancer disease free survival

Abstract

Abstract Objective. Vitamin D deficiency has been associated with poor outcomes in patients with breast cancer. The objective of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in 7 Vitamin D-related genes and disease free survival (DFS). We hypothesized that vitamin D-related genes may modify breast cancer DFS. Methods. A total of 102 SNPs in Vitamin D pathway genes were explored as predictors of DFS among 1030 stage I/II breast cancer patients treated at MD Anderson Cancer Center between 1985 and 2000. Genotyping was performed using the Illumina GoldenGate array. We applied recursive partitioning tree analysis (RPART) to explore interactions of variables predictive of DFS including vitamin D-related SNPs, age at diagnosis, race, stage, nuclear grade, estrogen (ER) and progesterone (PR) receptor status, chemotherapy, hormone therapy and BMI. Results. Results from partitioning identified chemotherapy as the optimum first split for DFS where patients receiving chemotherapy experienced longer DFS. In patients receiving chemotherapy (n=540), SNP rs1118569 (RXRA) followed by rs10881583 (RXRA) were associated with greater DFS. Patients with two major alleles of rs1118569 had the best outcome, whereas those with two minor alleles of rs10881583 and one or two minor rs1118569 alleles had poorer DFS. In patients who did not receive chemotherapy (n=482), stage I patients had longer DFS than stage II. Further, stage I patients who were homozygous for any allele of rs2248098 (VDR) had longer DFS. Among the stage II patients, those with ER/PR negative tumors had poorer DFS with heterozygous carriers of rs344781 in PLAUR having the worst DFS. Conclusion. While exploratory, we show that chemotherapy, stage, ER and PR status and vitamin D-related pathway polymorphisms but not race/ethnicity modified disease free survival in early stage breast cancer patients. Validation of vitamin D-related pathway genes as genetic determinants of patient outcomes would offer insights on alternative approaches for the secondary prevention of breast cancer recurrence considering clinical pathological and treatment characteristics of the patient population. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2607. doi:1538-7445.AM2012-2607