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.