Ahles Tim A, Saykin Andrew J, Noll Walter W, Furstenberg Charlotte T, Guerin Stephen, Cole Bernard, Mott Leila A
Department of Psychiatry and Center for Psycho-Oncology Research, USA.
Psychooncology. 2003 Sep;12(6):612-9. doi: 10.1002/pon.742.
The primary purpose of this study was to compare the neuropsychological performance of long-term survivors of breast cancer and lymphoma treated with standard dose chemotherapy who carried the epsilon 4 allele of the Apolipoprotein E (APOE) gene to those who carry other APOE alleles.
Long-term survivors (mean=8.8+/-4.3 years post-treatment) of breast cancer (N=51, age=55.9+/-8.8) or lymphoma (N=29, age=55.8+/-11.6) who had been treated with standard-dose chemotherapy completed a standardized battery of neuropsychological and psychological tests. Survivors were also classified into two groups based on the presence (N=17) or absence (N=63) of at least one epsilon 4 allele of APOE.
Analysis of covariance, controlling for age, gender, education, diagnosis, and WRAT-3 reading subtest (a proxy measure of baseline IQ), indicated that survivors with at least one epsilon 4 allele scored significantly lower in the visual memory (p<0.03) and the spatial ability (p<0.05) domains and tended to score lower in the psychomotor functioning (p<0.08) domain as compared to survivors who did not carry an epsilon 4 allele. No group differences were found on depression, anxiety, or fatigue.
The results of this study provide preliminary support for the hypothesis that the epsilon 4 allele of APOE may be a potential genetic marker for increased vulnerability to chemotherapy-induced cognitive decline.
本研究的主要目的是比较接受标准剂量化疗的乳腺癌和淋巴瘤长期幸存者中携带载脂蛋白E(APOE)基因ε4等位基因者与携带其他APOE等位基因者的神经心理学表现。
接受标准剂量化疗的乳腺癌(N = 51,年龄 = 55.9±8.8)或淋巴瘤(N = 29,年龄 = 55.8±11.6)长期幸存者(治疗后平均8.8±4.3年)完成了一系列标准化的神经心理学和心理测试。幸存者还根据是否存在至少一个APOEε4等位基因分为两组(存在组N = 17,不存在组N = 63)。
协方差分析在控制年龄、性别、教育程度、诊断和WRAT - 3阅读子测试(基线智商的替代指标)后表明,与未携带ε4等位基因的幸存者相比,携带至少一个ε4等位基因的幸存者在视觉记忆(p<0.03)和空间能力(p<0.05)领域得分显著更低,并且在心理运动功能(p<0.08)领域得分往往更低。在抑郁、焦虑或疲劳方面未发现组间差异。
本研究结果为以下假设提供了初步支持,即APOEε4等位基因可能是化疗诱导的认知功能下降易感性增加的潜在遗传标志物。