| Background The different molecular classification of breast cancer survivors had different treatment and prognosis,chemotherapy was one of the important means of treatment in breast cancer patients.It has been confirmed that cognitive impairment to some extent exists in breast cancer patients after chemotherapy,and the differences in gene expression about catechol-O-methyl transferase(COMT),apolipoprotein E(APOE),and brain derived neurotrophic factor(BDNF)were closely associated with cognitive function.Whetherthe COMT,APOE and BDNF gene polymorphisms modulate chemotherapy-induced cognitive impairment in triple negative breast cancer(TNBC)survivors,it was not clear at present.Objective The present study aimed to investigate the effect of genetic polymorphisms of COMT,APOE and BDNF on the modulation of the chemotherapy-induced cognitive impairment(CICI)in breast cancer patients.Methods Eighty triple negative breast cancer(TNBC)and 165 age-and education-matched non-triple negative breast cancer(NTNBC)patients were selected,and subjected to a number of neuropsychological tests,including Prospective memory(PM)and Retrospective memory(RM)questionnaires,before and after chemotherapy.Six single-nucleotide polymorphisms(SNPs),including COMT(rs165599,rs4680,rs737865),APOE(rs429358,rs7412),and BDNF(rs6265),were evaluated.The correlation analysis between each genetic locusand CICI was further studied.Results 1)The MMSE was significantly decreased to 26.76 ± 1.62 after chemotherapy as compared to that of before chemotherapy(27.26 ±1.58,*: p < 0.01),and similarly DST and VFT scores were also significantly decreased to 5.78 ± 0.97and11.46 ±1.52,respectively,after chemotherapy when compared to that before chemotherapy(6.19 ± 0.73,*: p < 0.01;and 11.46 ± 1.52,*: p < 0.01,respectively).The average RM score was significantly increased to 17.21 ± 4.59 after chemotherapy as compared to that before chemotherapy(16.23 ± 4.03,*: p < 0.01),and similarly,the average PM score was also significantly increased to 18.20 ± 4.51 after chemotherapy as compared to that before chemotherapy(16.01 ± 4.64,*: p < 0.01).2)The MMSE score after chemotherapy in the TNBC group(26.20±1.67)was significantly lower than that in the NTNBC group(27.03±1.52,*: p< 0.01),and similarly,the DST and VFT values after chemotherapy(5.29±1.01 and 8.40±1.65,respectively)in the TNBC group were also significantly lower than in the NTNBC group(6.02±0.86,*: p< 0.01,and 10.76±1.87,*: p< 0.01,respectively).The average RM score after chemotherapy in the TNBC group(19.10±2.36)was significantly higher than that in the NTNBC group(16.29±5.10,*: p < 0.01),and similarly,the average PM score after chemotherapy in the TNBC group(20.44±3.41)was significantly higher than that in the NTNBC group(17.12 ±4.58,*: p < 0.01).3)For the tested 6 SNPs,logistic regression analysis results showed that the patients with the GA(adjusted,OR=0.515,95%CI =0.272-0.977,p =0.048)and AA(adjusted,OR=0.318,95%CI =0.136-0.742,p =0.048)genotypes of COMT rs165599 had significantly lower odds of developing cognitive decline than the patients with the G/G genotype.Neither APOE(rs429358,rs7412)nor BDNF(rs6265)showed any statistically significant differences between the two groups.4)The correlation analysis between CMOT(rs165599)and CICI was further studied.Specifically,the dominant model(β=-1.441,CI(95%)=-2.781~-0.101)was found to be significantly associated with respective memory scores.Conclusion This study suggests that CICI in TNBC patients was more prominent than that in NTNBC patients after chemotherapy,and the COMT(rs165599)polymorphism was linear to the retrospective memory(RM)scores,and may be a potential genetic marker for increased vulnerability to CICI in TNBC patients. |
PDF Full Text Request