DNA Repair/Oxidative Stress Genes and Pain in Cancer Survivors on Aromatase Inhibitors

Abstract

Abstract Purpose Pain is a problem in women with breast cancer prescribed aromatase inhibitors (AIs). DNA repair/oxidative stress genes are implicated in the development of pain and cancer. This study examined the relationship between polymorphisms in DNA repair/oxidative stress genes and pain in postmenopausal women with breast cancer over time. Methods Single nucleotide polymorphisms (SNPs) of select DNA repair/oxidative stress genes were genotyped, and perceived average pain was assessed in women with breast cancer prior to and throughout adjuvant therapy (AI ± chemotherapy; n = 138) and healthy controls (n = 81). Cragg two-equation hurdle regression was used to evaluate the relationship between each associated allele and (1) chances of having any pain, and (2) pain severity ≥ 1. Results As the number of associated alleles increased, so did odds of any pain and pain severity. At baseline, odds of pain were associated with allele combinations from four SNPs (OR = 1.49; 95% CI = 1.16–1.92; p < 0.001), while greater severity was associated with alleles from three SNPs (CME = 0.33; 95% CI = 0.16–0.50; p < 0.001). After 6 months, a combination of alleles from six genes impacted the odds of any pain (OR = 1.24; 95% CI = 1.04–1.48; p = 0.018), but severity was not associated. Conclusions SNPs in DNA repair/oxidative stress pathways play a role in odds of pain prior to AI therapy and at 6 months, but different SNPs are associated at different timepoints. Implication for Cancer Survivors - Biomarker testing for implicated SNPs can be used to detect individuals at risk for cancer pain development. These individuals can be provided prophylactic pain interventions to decrease pain severity.