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COMT rs737865 mediates chemobrain in breast cancer patients with various levels of Ki-67.

Previous findings have indicated that catechol-O-methyltransferase (COMT) may be a genetic risk factor for chemobrain. However, the mediation of chemobrain by COMT polymorphisms in breast cancer patients with various levels of Ki-67 remains unknown. The current research assessed the genetic risk across COMT genotypes for chemobrain in breast cancer patients with various levels of Ki-67. Breast cancer patients (65 with Ki-67<14%, 75 with Ki-67>14%) completed cognitive tests before and after adjuvant chemotherapy, and three single-nucleotide polymorphisms (SNPs) of COMT (rs165599, rs4680, rs737865) were genotyped from peripheral blood. Lower cognitive test results in breast cancer patients were displayed in those before chemotherapy. Furthermore, the event-based prospective memory (EBPM) scores of patients in the Ki-67>14% group were worse than those in the patients in the Ki-67<14% group after chemotherapy (z=-7.51, P<0.01), but the time-based prospective memory (TBPM) scores of the two groups were not significantly different. The COMT rs737865 A/G genotype was associated with memory protection (codominant model: adjusted odds ratio (OR)=0.135, 95% CI=0.026-0.706, P=0.018), and A/G genotype carriers exhibited better performance on the EBPM test than the A/A genotype. Levels of Ki-67 were likely to be associated with EBPM decline in breast cancer patients. Taken together, COMT rs737865 polymorphisms are a potential genetic risk factor for chemobrain in breast cancer patients with various levels of Ki-67.