Abstract 807: Polymorphisms in DNA-repair genes and its association with pain among breast cancer patients receiving adjuvant radiation therapy

Abstract

Abstract Pain related to cancer or treatments is a critical quality of life (QOL) issue for breast cancer survivors. This study aimed to evaluate the association between the polymorphisms in DNA-repair genes and radiation therapy (RT)-associated pain among breast cancer patients receiving adjuvant RT. Pain score was assessed at pre- and post-RT as the mean of four pain severity items (i.e., pain at its worst, least, average, and now) from the Brief Pain Inventory with 11-point numeric rating scale (0-10) and RT-associated clinically relevant pain was considered present when pain score increased from <4 to ≥ 4 during RT. We evaluated 3,747 single-nucleotide polymorphisms (SNPs) in 119 DNA repair-related genes; 15 genes in base excision repair (BER), 11 in mismatch repair (MMR), 26 in nucleotide excision repair (NER), 15 in homologous recombination, 5 in non-homologous end-joining (NHEJ), 15 in DNA polymerase, and 47 in other DNA repair-related pathways. Multiple logistic regression analyses were conducted to assess the associations between SNPs and RT-associated pain. In a prospective study of 359 breast cancer patients, 81 experienced RT-associated pain. After controlling for significant covariates, 232 SNPs were found significant at p <0.05 and 48 at p < 0.01. Significant associations (p<0.01) were found in 11 SNPs in XRCC4 and 3 in XRCC5 in NHEJ, 7 in ATR in DNA damage response pathway, 6 in MGMT in direct reversal of damage pathway, 6 in MSH3 and 1 in PMS1 in MMR, 3 in XRCC1 genes in BER, 2 in POLB and POLB, and 1 in REV1 in DNA polymerase pathway, 1 in XPC and RPA3 in NER, and 1 in UBE2V2 in Rad6 pathway. Among these, most significant association was found in SNP in ATR serine/threonine kinase (rs13099184) which showed that carrying one or two doses of minor T allele was associated with increased risk of experiencing RT-associated pain (odds ratio [OR] = 2.33; 95% confidence interval (CI) = 1.53-3.55, p = 8.52×10-5). For XRCC4 (rs2089565), carriers with one or two minor C allele were more likely to experience RT-associated pain (OR = 1.93, 95% CI = 1.31-2.84, p = 8.1×10-4). This study demonstrated that genetic variations in multiple genes in DNA-repair pathways may contribute to inter-individual variation in pain experience among cancer patients during RT. After validation with a larger sample, these findings may be used as predictive biomarkers of radiation sensitivity which allows to identify patients at high risk of pain. Also the results can provide biological targets for early intervention for pain management to improve QOL in breast cancer survivors. Citation Format: Eunkyung Lee, Jean L. Wright, Cristiane Takita, Eden Martin, Susan Slifer, Jennifer J. Hu. Polymorphisms in DNA-repair genes and its association with pain among breast cancer patients receiving adjuvant radiation therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 807.