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The COMT (rs165599) gene polymorphism contributes to chemotherapy-induced cognitive impairment in breast cancer patients.

ABSTRACT: The present study aimed to investigate the effect of genetic polymorphisms of catechol-O-methyl transferase (COMT), apolipoprotein E (APOE), and brain derived neurotrophic factor (BDNF) on the modulation of the chemotherapy-induced cognitive impairment (CICI) in breast cancer patients. Eighty triple negative breast cancer (TNBC) and 165 non-triple negative breast cancer (NTNBC) patients were selected, and subjected to a number of neuropsychological tests, including memory questionnaires, before and after chemotherapy. Six single-nucleotide polymorphisms (SNPs), including COMT (rs165599, rs4680, rs737865), APOE (rs429358, rs7412), and BDNF (rs6265), were evaluated. The scores of breast cancer patients after chemotherapy were poorer in comparison to those before chemotherapy (t = -5.317, z = -3.372, respectively, P < 0.01), and the scores of TNBC patients were poorer than those of NTNBC patients were after chemotherapy (t = -5.997, z = -5.284, respectively, P < 0.01). Patients with the COMT (rs165599) genotype had a significantly lower chance of developing cognitive decline than the patients with the G/G genotype, and this was linear with the retrospective memory (RM) questionnaires (? = -1.441, CI (95%) = -2.781~-0.101). However, there was no significant difference between the memory scores of APOE (rs429358, rs7412) and BDNF (rs6265) carriers before or after chemotherapy. 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) questionnaires, and may be a potential genetic marker for increased vulnerability to CICI in TNBC patients.

SUBMITTER: Cheng H

PROVIDER: S-EPMC5126352 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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The COMT (rs165599) gene polymorphism contributes to chemotherapy-induced cognitive impairment in breast cancer patients.

Cheng Huaidong H Li Wen W Gan Chen C Zhang Bo B Jia Qianqian Q Wang Kai K

American journal of translational research 20161115 11

The present study aimed to investigate the effect of genetic polymorphisms of catechol-O-methyl transferase (COMT), apolipoprotein E (APOE), and brain derived neurotrophic factor (BDNF) on the modulation of the chemotherapy-induced cognitive impairment (CICI) in breast cancer patients. Eighty triple negative breast cancer (TNBC) and 165 non-triple negative breast cancer (NTNBC) patients were selected, and subjected to a number of neuropsychological tests, including memory questionnaires, before ...[more]

PMID: 27904710

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Project description:Math anxiety (MA) is a phobic reaction to math activities, potentially impairing math achievement. Higher frequency of MA in females is explainable by the interaction between genetic and environmental factors. The molecular-genetic basis of MA has not been investigated. The COMT Val158Met polymorphism, which affects dopamine levels in the prefrontal cortex, has been associated with anxiety manifestations. The valine allele is associated with lower, and the methionine allele with higher, dopamine availability. In the present study, the effects of sex and COMT Val158Met genotypes on MA were investigated: 389 school children aged 7-12 years were assessed for intelligence, numerical estimation, arithmetic achievement and MA and genotyped for COMT Val158Met polymorphism. The Math Anxiety Questionnaire (MAQ) was used to assess the cognitive and affective components of MA. All genotype groups of boys and girls were comparable regarding genotype frequency, age, school grade, numerical estimation, and arithmetic abilities. We compared the results of all possible genetic models: codominance (Val/Val vs. Val/Met vs. Met/Met), heterosis (Val/Met vs. Val/Val plus Met/Met), valine dominance (Val/Val plus Val/Met vs. Met/Met), and methionine dominance (Met/Met plus Val/Met vs. Val/Val). Models were compared using AIC and AIC weights. No significant differences between girls and boys and no effects of the COMT Val158Met polymorphism on numerical estimation and arithmetic achievement were observed. Sex by genotype effects were significant for intelligence and MA. Intelligence scores were higher in Met/Met girls than in girls with at least one valine allele (valine dominance model). The best fitting model for MA was heterosis. In Anxiety Toward Mathematics, heterozygous individuals presented MA levels close to the grand average regardless of sex. Homozygous boys were significantly less and homozygous girls significantly more math anxious. Heterosis has been seldom explored, but in recent years has emerged as the best genetic model for some phenotypes associated with the COMT Val158Met polymorphism. This is the first study to investigate the genetic-molecular basis of MA.

Project description:A highly polymorphic T homopolymer was recently found to be associated with late-onset Alzheimer's disease risk and age of onset.To explore the effects of the polymorphic polyT tract (rs10524523, referred as '523') on cognitive performance in cognitively healthy elderly individuals.One hundred eighty-one participants were recruited from local independent-living retirement communities. Informed consent was obtained, and participants completed demographic questionnaires, a conventional paper-and-pencil neuropsychological battery, and the computerized Cambridge Neuropsychological Test Automated Battery (CANTAB). Saliva samples were collected for determination of the TOMM40 '523' (S, L, VL) and the apolipoprotein E (APOE) (?2, 3, 4) genotypes. From the initial sample of 181 individuals, 127 were eligible for the association analysis. Participants were divided into three groups based on '523' genotypes (S/S, S/L-S/VL, and L/L-L/VL-VL/VL). Generalized linear models were used to evaluate the association between the '523' genotypes and neuropsychological test performance. Analyses were adjusted for age, sex, education, depression, and APOE ?4 status. A planned subanalysis was undertaken to evaluate the association between '523' genotypes and test performance in a sample restricted to APOE ?3 homozygotes.The S homozygotes performed better, although not significantly, than the S/L-S/VL and the VL/L-L/VL-VL/VL genotype groups on measures associated with memory (CANTAB Paired Associates Learning, Verbal Recognition Memory free recall) and executive function (CANTAB measures of Intra-Extra Dimensional Set Shift). Follow-up analysis of APOE ?3 homozygotes only showed that the S/S group performed significantly better than the S/VL group on measures of episodic memory (CANTAB Paired Associates Learning and Verbal Recognition Memory free recall), attention (CANTAB Rapid Visual Information Processing latency), and executive function (Digit Symbol Substitution). The S/S group performed marginally better than the VL/VL group on Intra-Extra Dimensional Set Shift. None of the associations remained significant after applying a Bonferroni correction for multiple testing.Results suggest important APOE-independent associations between the TOMM40 '523' polymorphism and specific cognitive domains of memory and executive control that are preferentially affected in early-stage Alzheimer's disease.

Dataset Information

The COMT (rs165599) gene polymorphism contributes to chemotherapy-induced cognitive impairment in breast cancer patients.

Publications

The COMT (rs165599) gene polymorphism contributes to chemotherapy-induced cognitive impairment in breast cancer patients.

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