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Exploratory Study of Associations Between DNA Repair and Oxidative Stress Gene Polymorphisms and Cognitive Problems Reported by Postmenopausal Women With and Without Breast Cancer.

ABSTRACT: PURPOSE:Women with breast cancer report varying frequencies of cognitive problems during adjuvant systemic therapy. This variability suggests latent subgroups. Therefore, we identified latent subgroups of self-reported cognitive problems among postmenopausal women with and without breast cancer. We explored associations between membership in these subgroups and (a) demographic, clinical, and symptom characteristics and (b) variations in candidate gene polymorphisms. METHODS:We evaluated frequency of cognitive problems using the Patient Assessment of Own Functioning Inventory. Growth mixture modeling identified latent subgroups over 18 months of adjuvant systemic therapy and at matched time points for women without cancer ( N = 331). We evaluated for differences among subgroups in demographic, clinical, and symptom characteristics and in 41 single nucleotide polymorphisms in 10 candidate genes involved in DNA repair and oxidative stress pathways ( n = 199). We modeled associations between genotypes and subgroup membership using multinomial logistic regression. RESULTS:We identified three latent subgroups: more frequent, persistent, and almost never. Receipt of chemotherapy plus anastrozole, depressive symptoms, and baseline neuropathic symptoms increased the odds of belonging to the more frequent subgroup. Anxiety and depressive symptoms increased the odds of belonging to the persistent subgroup. With covariates controlled for, carrying the ERCC5 rs873601 G minor allele increased the odds of reporting more frequent cognitive problems. CONCLUSIONS:Chemotherapy plus anastrozole, depressive symptoms, and presence of neuropathic symptoms may predict more frequent cognitive problems during systemic therapy that later resolve. Mood dysregulation before therapy may predict persistent cognitive problems during therapy. ERCC5 genotype may influence frequency of cognitive problems after controlling for these risk factors.

SUBMITTER: Merriman JD

PROVIDER: S-EPMC6700884 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Exploratory Study of Associations Between DNA Repair and Oxidative Stress Gene Polymorphisms and Cognitive Problems Reported by Postmenopausal Women With and Without Breast Cancer.

Merriman John D JD Sereika Susan M SM Conley Yvette P YP Koleck Theresa A TA Zhu Yehui Y Phillips Mary L ML Bertocci Michele A MA Brufsky Adam M AM Bender Catherine M CM

Biological research for nursing 20180913 1

<h4>Purpose</h4>Women with breast cancer report varying frequencies of cognitive problems during adjuvant systemic therapy. This variability suggests latent subgroups. Therefore, we identified latent subgroups of self-reported cognitive problems among postmenopausal women with and without breast cancer. We explored associations between membership in these subgroups and (a) demographic, clinical, and symptom characteristics and (b) variations in candidate gene polymorphisms.<h4>Methods</h4>We eva ...[more]

PMID: 30213196

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Project description:BackgroundLittle is known regarding the association of interviewer-reported cognitive problems (ICP) with age-related cognitive decline. We aimed to investigate the independent associations of ICP and the combined associations of ICP and self-reported cognitive problems (SCP) with subsequent cognitive decline and dementia in two prospective cohort studies.MethodsWe included 10,976 Chinese (age = 57.7 ± 8.7) and 40,499 European (age = 64.6 ± 9.4) adults without dementia from the China Health and Retirement Longitudinal Study (CHARLS) and the Survey of Health, Ageing, and Retirement in Europe (SHARE). Self-rated memory (5-point scale) and interviewer-rated frequencies of asking for clarification (6-point scale) were used to define SCP and ICP (dichotomized). Outcomes included objective cognitive test scores (z-score transformation) and incident dementia. Generalized estimating equation models were performed to evaluate mean differences in objective cognitive decline. Logistic and Cox regression models were used to estimate the relative risk of dementia. Results from two cohorts were pooled using the random-effects models.ResultsICP was associated with faster cognitive decline in CHARLS (βCHARLS = -0.025 [-0.044, -0.006] z-score/year). ICP and SCP were also independently associated with higher risk of dementia in two cohorts (pooled relative risk for SCP = 1.73 [1.30, 2.29]; pooled relative risk for ICP = 1.40 [1.10, 1.79]). In the joint analysis, participants with coexistence of SCP and ICP had the fastest cognitive decline (βCHARLS = -0.051 [-0.080, -0.021]; βSHARE = -0.024 [-0.043, -0.004]; pooled β = -0.035 [-0.061, -0.009] z-score/year) and highest risk of dementia (ORCHARLS = 1.77 [1.42, 2.20]; HRSHARE = 2.94 [2.42, 3.59]; pooled relative risk = 2.29 [1.38, 3.77]).ConclusionsThe study suggested that interviewer-reported cognitive problems may be early indicators of cognitive decline and dementia in middle-aged and older adults. A combination of self- and interviewer-reported cognitive problems showed the strongest associations with cognitive decline and dementia.

Dataset Information

Exploratory Study of Associations Between DNA Repair and Oxidative Stress Gene Polymorphisms and Cognitive Problems Reported by Postmenopausal Women With and Without Breast Cancer.

Publications

Exploratory Study of Associations Between DNA Repair and Oxidative Stress Gene Polymorphisms and Cognitive Problems Reported by Postmenopausal Women With and Without Breast Cancer.

Similar Datasets

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