GSK3β rs3107669 polymorphism implicates chemotherapy-associated retrospective memory deficits in breast cancer survivors

Glycogen synthase kinase-3β (GSK-3β) plays an important role in the development of neurodegenerative diseases. However, the underlying effect of GSK-3β polymorphism on chemobrain in cancer survivors is unclear. This study aimed to evaluate the correlation between GSK-3β polymorphism and chemotherapy-associated retrospective memory deficits in breast cancer survivors. The difference in GSK-3β gene expression between breast cancer patients and healthy controls was confirmed using bioinformatics technology. All participants (197 with breast cancer and 40 healthy controls) underwent prospective and retrospective memory tests, and five single-nucleotide polymorphism loci of GSK-3β (rs3107669, rs1154597, rs334543, rs334558 and rs3755557) were genotyped from peripheral blood. Breast cancer survivors had memory impairment after chemotherapy (P<0.0001). The expression difference of the GSK-3β gene was determined through bioinformation analysis, and a genotype frequency difference of GSK-3β rs3107669 was found between the breast cancer and healthy control groups. GSK-3β rs3107669 was a genetic risk in comparison to the healthy controls (OR=0.382; 95% CI=0.186-0.786; P=0.009). Breast cancer with the GSK-3β rs3107669 (C/A+A/A) genotype was a protective factor for chemobrain (Beta=-0.306; 95% CI=-5.556~-2.145; P<0.0001) from multiple linear regression. The C/A+A/A genotype carrier performed better on the retrospective memory test than the C/C genotype (z=-4.302, P<0.0001). Breast cancer patients with chemotherapy who also carried the GSK-3β rs3107669 (C/C) genotype more easily presented cognitive deficits. The GSK-3β rs3107669 polymorphism was a feasible genetic risk factor for chemotherapy-associated retrospective memory impairments in breast cancer survivors.