Genetic polymorphisms in DNA repair and oxidative stress pathways may modify the association between body size and postmenopausal breast cancer

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.

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Polymorphisms in DNA repair and oxidative stress genes associated with pre-treatment cognitive function in breast cancer survivors: an exploratory study

SpringerPlus ◽

10.1186/s40064-016-2061-4 ◽

2016 ◽

Vol 5 (1) ◽

Cited By ~ 9

Author(s):

Theresa A. Koleck ◽

Catherine M. Bender ◽

Susan M. Sereika ◽

Adam M. Brufsky ◽

Barry C. Lembersky ◽

...

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Dna Repair ◽

Cognitive Function ◽

Cancer Survivors ◽

Exploratory Study ◽

Breast Cancer Survivors ◽

Stress Genes ◽

Pre Treatment ◽

And Oxidative Stress

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Tamoxifen and oxidative stress: an overlooked connection

Discover Oncology ◽

10.1007/s12672-021-00411-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Nermin S. Ahmed ◽

Marek Samec ◽

Alena Liskova ◽

Peter Kubatka ◽

Luciano Saso

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Gold Standard ◽

Pharmacological Activities ◽

Standard Drug ◽

Menopausal Women ◽

Wide Range ◽

Post Menopausal ◽

Apoptotic Effects ◽

And Oxidative Stress

AbstractTamoxifen is the gold standard drug for the treatment of breast cancer in pre and post-menopausal women. Its journey from a failing contraceptive to a blockbuster is an example of pharmaceutical innovation challenges. Tamoxifen has a wide range of pharmacological activities; a drug that was initially thought to work via a simple Estrogen receptor (ER) mechanism was proven to mediate its activity through several non-ER mechanisms. Here in we review the previous literature describing ER and non-ER targets of tamoxifen, we highlighted the overlooked connection between tamoxifen, tamoxifen apoptotic effects and oxidative stress.

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Polymorphisms in oxidative stress-related genes and postmenopausal breast cancer risk

International Journal of Cancer ◽

10.1002/ijc.25761 ◽

2011 ◽

Vol 129 (6) ◽

pp. 1467-1476 ◽

Cited By ~ 23

Author(s):

Petra Seibold ◽

Rebecca Hein ◽

Peter Schmezer ◽

Per Hall ◽

Jianjun Liu ◽

...

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Postmenopausal Breast Cancer ◽

Postmenopausal Breast Cancer Risk ◽

Stress Related Genes

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Aging and oxidative stress alter DNA repair mechanisms in male germ cells of superoxide dismutase-1 null mice

Biology of Reproduction ◽

10.1093/biolre/ioab114 ◽

2021 ◽

Author(s):

Paulina Nguyen-Powanda ◽

Bernard Robaire

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Dna Repair ◽

Superoxide Dismutase ◽

Germ Cells ◽

Superoxide Dismutase 1 ◽

Male Germ Cells ◽

Dna Repair Mechanisms ◽

Repair Mechanisms ◽

And Oxidative Stress

Abstract The efficiency of antioxidant defense system decreases with aging, thus resulting in high levels of reactive oxygen species (ROS) and DNA damage in spermatozoa. This damage can lead to genetic disorders in the offspring. There are limited studies investigating the effects of the total loss of antioxidants, such as superoxide dismutase-1 (SOD1), in male germ cells as they progress through spermatogenesis. In this study, we evaluated the effects of aging and removing SOD1 (in male germ cells of SOD1-null (Sod1−/−) mice) in order to determine the potential mechanism(s) of DNA damage in these cells. Immunohistochemical analysis showed an increase in lipid peroxidation and DNA damage in the germ cells of aged wild-type (WT) and Sod1−/− mice of all age. Immunostaining of OGG1, a marker of base excision repair (BER), increased in aged WT and young Sod1−/− mice. In contrast, immunostaining intensity of LIGIV and RAD51, markers of non-homologous end-joining (NHEJ) and homologous recombination (HR), respectively, decreased in aged and Sod1−/− mice. Gene expression analysis showed similar results with altered mRNA expression of these key DNA repair transcripts in pachytene spermatocytes and round spermatids of aged and Sod1−/− mice. Our study indicates that DNA repair pathway markers of BER, NHEJ, and HR are differentially regulated as a function of aging and oxidative stress in spermatocytes and spermatids, and aging enhances the repair response to increased oxidative DNA damage, whereas impairments in other DNA repair mechanisms may contribute to the increase in DNA damage caused by aging and the loss of SOD1.

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