The association of genetic polymorphisms with neuroconnectivity in breast cancer patients

Harrison, Rebecca; Rao, Vikram; Kesler, Shelli R.

doi:10.1038/s41598-021-85768-4

Cited by 12 publications

(9 citation statements)

References 82 publications

(101 reference statements)

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“…Accordingly, carriers of this allele are at increased risk for neurodegenerative conditions that affect cognition. Our group and others have shown that the APOE e4 genotypic variant is associated with lower cognitive function in breast cancer (23)(24)(25). We also previously demonstrated a potentially altered relationship between APOE genotype and neurogenesis in patients with breast cancer (23) and there is some evidence suggesting an association between APOE e4 genotype and breast cancer pathogenesis (26).…”

Section: Introductionmentioning

confidence: 58%

Behavioral and Biologic Characteristics of Cancer-related Cognitive Impairment Biotypes

Mulholland

Prinsloo

Kvale

et al. 2022

Preprint

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Psychiatric diagnosis is moving away from symptom-based classification and towards multi-dimensional, biologically-based characterization, or biotyping. We previously identified three biotypes of chemotherapy-related cognitive impairment based on functional brain connectivity. In this follow-up study, we evaluated additional factors to help explain biotype expression: neurofunctional stability, brain age, apolipoprotein (APOE) genotype, and psychoneurologic symptoms. We also compared the discriminative ability of a traditional, symptom-based cognitive impairment definition with that of biotypes. We found significant differences in cortical brain age (F = 10.86, p < 0.001), neurofunctional stability (F = 2.85, p = 0.040), APOE e4 genotype (X2 = 7.89, p = 0.048), and psychoneurological symptoms (Pillai = 0.339, p < 0.001) across the three biotypes. The more resilient (Biotype 2) demonstrated significantly higher neurofunctional stability compared to the other biotypes. Symptom-based classification of cognitive impairment did not differentiate biologic or other behavioral variables, suggesting that traditional categorization of cancer-related cognitive effects may miss important characteristics which could inform targeted treatment strategies. Additionally, biotyping, but not symptom-typing, was able to distinguish survivors with cognitive versus psychological effects. Our results suggest that Biotype 1 survivors might benefit from first addressing symptoms of anxiety and fatigue, Biotype 3 might benefit from a treatment plan which includes sleep hygiene, and Biotype 2 might benefit most from cognitive skills training or rehabilitation. Future research should include additional demographic and clinical information to further investigate biotype expression related to risk and resilience and examine integration of more clinically feasible imaging approaches.

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Section: Introductionmentioning

confidence: 58%

Behavioral and Biologic Characteristics of Cancer-related Cognitive Impairment Biotypes

Mulholland

Prinsloo

Kvale

et al. 2022

Preprint

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“…Neuroimaging studies suggest that cancer-related cognitive impairment (CRCI) results from injury to brain structure and function. We previously showed that breast cancer survivors have altered brain network connectivity compared to healthy controls and chemotherapy naïve survivors (3)(4)(5)(6)(7)(8)(9). Other groups have subsequently observed similar findings (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 70%

“…Although many studies have demonstrated that primary breast cancer and/or its treatments significantly alter brain function and structure, it remains unclear how or why. Several studies, including our own, suggest genetic and/or epigenetic risk factors may play an important role (9,39,(65)(66)(67)(68)(69). However, these findings have been limited to the candidate variants selected and have shown some inconsistent results, which may relate to what brain regions were examined.…”

Section: Discussionmentioning

confidence: 89%

Cross-Sectional Characterization of Local Brain Network Connectivity Pre and Post Breast Cancer Treatment and Distinct Association With Subjective Cognitive and Psychological Function

et al. 2021

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Objective: We aimed to characterize local brain network connectivity in long-term breast cancer survivors compared to newly diagnosed patients.Methods: Functional magnetic resonance imaging (fMRI) and subjective cognitive and psychological function data were obtained from a group of 76 newly diagnosed, pre-treatment female patients with breast cancer (mean age 57 ± 7 years) and a separate group of 80, post-treatment, female breast cancer survivors (mean age 58 ± 8; mean time since treatment 44 ± 43 months). The network-based statistic (NBS) was used to compare connectivity of local brain edges between groups. Hubs were defined as nodes with connectivity indices one standard deviation or more above network mean and were further classified as provincial (higher intra-subnetwork connectivity) or connector (higher inter-subnetwork connectivity) using the participation coefficient. We determined the hub status of nodes encompassing significantly different edges and correlated the centralities of edges with behavioral measures.Results: The post-treatment group demonstrated significantly lower subjective cognitive function (W = 3,856, p = 0.004) but there were no group differences in psychological distress (W = 2,866, p = 0.627). NBS indicated significantly altered connectivity (p < 0.042, corrected) in the post-treatment group compared to the pre-treatment group largely in temporal, frontal-temporal and temporal-parietal areas. The majority of the regions projecting these connections (78%) met criteria for hub status and significantly less of these hubs were connectors in the post-treatment group (z = 1.85, p = 0.031). Subjective cognitive function and psychological distress were correlated with largely non-overlapping edges in the post-treatment group (p < 0.05).Conclusion: Widespread functional network alterations are evident in long-term survivors of breast cancer compared to newly diagnosed patients. We also demonstrated that there are both overlapping and unique brain network signatures for subjective cognitive function vs. psychological distress.

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“…Matsuzaka et al (51) showed the relationship between the two SNPs of the COMT (rs165599 and rs737865) and working memory; the cognition in schizophrenia patients may be modulated by COMT. Compared with healthy controls, breast cancer patients receiving chemotherapy had slower treatment speed and poorer executive function, while apolipoprotein E (APOE) and COMT gene polymorphisms were associated with cognitive impairment (52).Our previous research findings indicated that COMT (rs165599) was a risk-related genetic factor influencing CRCI in TNBC patients (23). Further study found that COMT (rs737865) was correlated with EBPM damage following chemotherapy in breast cancer with different expressions of hormone receptor (24).…”

Section: Discussionmentioning

confidence: 99%

The COMT Genetic Factor Regulates Chemotherapy-Related Prospective Memory Impairment in Survivors With HER2−/+ Breast Cancer

Zhang

Cai

et al. 2022

Front. Oncol.

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BackgroundPrevious findings indicated that polymorphism in gene catechol-O-methyltransferase (COMT) had been linked to chemotherapy-related cognitive impairment (CRCI). Nevertheless, the motivation of COMT polymorphisms in regulating cognitive impairment in breast cancer survivors with disparate status of human epidermal growth factor receptor 2 (HER2) was still vague.ObjectiveThe current research aimed to evaluate the regulation of the risk by COMT genotype on CRCI in breast cancer survivors with disparate status of HER2.MethodsBreast cancer survivors (103 with HER2− and 118 with HER2+) underwent neuropsychological tests before and after chemotherapy, containing event- and time-based prospective memory (EBPM and TBPM). Three single-nucleotide polymorphisms (SNPs) were estimated by providing peripheral blood, containing COMT (rs165599, rs737865, and rs4680).ResultsThe EBPM and TBPM performances was lower as compared with these before chemotherapy (z = −7.712, z = −2.403, respectively, p < 0.01). Furthermore, the EBPM and TBPM performances of HER2− group survivors were lower than those of HER2+ group survivors after chemotherapy (z = −7.181, p < 0.01; z = −2.205 p < 0.05, respectively). The survivors with COMT (rs165599) A/A genotype carriers had a meaningfully poorer chance of memory descend [dominant model: adjusted, OR = 2.21, CI (95%) = 1.156–4.225, p = 0.016] and showed better on TBPM test, relative to G/G genotype. Patients with the COMT (rs737865) A/G and G/G genotype showed protective function than the patients with the A/A and performed better on MMSE and TBPM tests.ConclusionThe types of HER2 may be correlated to chemotherapy-related prospective memory impairments in breast cancer survivors. Furthermore, the COMT (rs165599, rs737865) polymorphisms were correlated to the risk of TBPM decline scores and possibly be a potential genetic identifying for increasing risk of CRCI in breast cancer patients with disparate status of HER2.

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The association of genetic polymorphisms with neuroconnectivity in breast cancer patients

Cited by 12 publications

References 82 publications

Behavioral and Biologic Characteristics of Cancer-related Cognitive Impairment Biotypes

Behavioral and Biologic Characteristics of Cancer-related Cognitive Impairment Biotypes

Cross-Sectional Characterization of Local Brain Network Connectivity Pre and Post Breast Cancer Treatment and Distinct Association With Subjective Cognitive and Psychological Function

The COMT Genetic Factor Regulates Chemotherapy-Related Prospective Memory Impairment in Survivors With HER2−/+ Breast Cancer

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