108P COMT, APOE, and BDNF gene polymorphisms modulate chemotherapy-induced cognitive impairment in breast cancer survivors

Abstract

Background TheaimofthisstudywastoinvestigatewhetherCOMT,APOEand BDNF gene polymorphisms modulate chemotherapy-induced cognitive impairment (CICI) in breast cancer survivors. Methods Eighty triple negative breast cancer (TNBC) and 165 non-triple negative breastcancer (NTNBC) matched forage and education wererespectivelyadministered withabatteryofneuropsychologicaltestsincludingmemoryquestionnairesbeforeand after chemotherapy. Six single-nucleotide polymorphisms (SNPs) within COMT (rs165599,rs4680,rs737865),APOE(rs429358,rs7412)andBDNF(rs6265)genewere evaluated. Results:Comparedwiththememoryscoresofbreastcancerpatientsbefore chemotherapy,thescoreofbreastcancerpatientsafterchemotherapywaspoorer, exhibitedsignificantdifference(t=-5.317,z = -3.372, respectively,p<0.01). Further, comparedwithNTNBCpatients,memoryscoresofTNBCwerepoorer,exhibited statisticalsignificancedifferenceafterchemotherapy(t=-5.997, z=-5.284, respectively, p<0.01).GenotypeoftheCOMTrs165599hadsignificantlyloweroddsofdeveloping cognitive decline than the patients with the G/G genotype. Neither APOE (rs429358, rs7412)orBDNF(rs6265)hadnostatisticallysignificantdifferencesbetweenthetwo groups. Further, linearregression revealedthatthedominantmodelofCOMT rs165599 (beta=-1.441,95%CI=-2.781~-0.101) wasfoundto be significantly associated with retrospective memory (RM) questionnaires. Conclusions The results suggests CICI in TNBC survivors were poorer than NTNBC after chemotherapy, and the COMT rs165599 polymorphism may be a potential genetic markerfor increased vulnerabilityto chemotherapy-induced memoryimpairmentin TNBC survivors. Legal entity responsible for the study N/A Funding National Natural Science Foundation ofChina Disclosure All authors have declared no conflicts ofinterest.