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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.

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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