Uomori Toshitaka, Horimoto Yoshiya, Mogushi Kaoru, Matsuoka Joe, Saito Mitsue
Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.
Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Breast Cancer. 2017 Sep;24(5):702-707. doi: 10.1007/s12282-017-0761-4. Epub 2017 Feb 20.
Chemotherapy-induced nausea and vomiting (CINV) can negatively affect quality of life and treatment compliance in breast cancer patients. Habitual alcohol consumption reportedly shows an inverse correlation with CINV, though the underlying mechanism is unknown. Acetaldehyde dehydrogenase 2 (ALDH2), one of the two ALDH isozymes, is reportedly the major factor among several genetic polymorphisms possibly affecting alcohol metabolism. More than 40% of Japanese have ALDH2 mutations, while almost all Westerners have the wild type. We hypothesized that ALDH2 polymorphism status might relate to the metabolism of emetic chemotherapeutic drugs. Relationships among habitual alcohol consumption, ALDH2 polymorphisms, and CINV in Japanese breast cancer patients given adjuvant chemotherapy containing high-emetic drugs were, thus, investigated.
We enrolled 81 women, between 20 and 55 years of age, who had been diagnosed with primary breast cancer and received (neo-) adjuvant chemotherapy at our institution. ALDH2 genotypes were analyzed employing the smart amplification process in peripheral blood samples.
The wild type (ALDH2*1/1), heterozygote (ALDH21/2), and mutant homozygote (ALDH22/*2) genotypes were found in 53, 44, and 3% of patients, respectively. Complete response, i.e., no vomiting without rescue anti-emetics, was more frequent in patients who habitually consumed alcohol than in those who did not (p = 0.036). This trend remained only in ALDH2 heterozygotes when patients were categorized according to ALDH2 genotype. Logistic regression analysis revealed alcohol intake to be an independent predictive factor for complete response (p = 0.013).
Our results revealed habitual alcohol intake to be related to a lower CINV incidence. The impact of alcohol intake on CINV in patients with ALDH2 polymorphisms merits further investigation.
化疗引起的恶心和呕吐（CINV）会对乳腺癌患者的生活质量和治疗依从性产生负面影响。据报道，习惯性饮酒与CINV呈负相关，但其潜在机制尚不清楚。乙醛脱氢酶2（ALDH2）是两种ALDH同工酶之一，据报道，它是可能影响酒精代谢的几种基因多态性中的主要因素。超过40%的日本人有ALDH2突变，而几乎所有西方人都是野生型。我们假设ALDH2基因多态性状态可能与催吐化疗药物的代谢有关。因此，我们研究了日本乳腺癌患者在接受含高致吐性药物的辅助化疗时，习惯性饮酒、ALDH2基因多态性与CINV之间的关系。
我们纳入了81名年龄在20至55岁之间、被诊断为原发性乳腺癌并在我们机构接受（新）辅助化疗的女性。采用智能扩增法分析外周血样本中的ALDH2基因型。
野生型（ALDH2*1/1）、杂合子（ALDH21/2）和突变纯合子（ALDH22/*2）基因型分别在53%、44%和3%的患者中发现。习惯性饮酒的患者完全缓解（即无需使用救援性止吐药即可无呕吐）的频率高于不饮酒的患者（p = 0.036）。当根据ALDH2基因型对患者进行分类时，这种趋势仅在ALDH2杂合子中存在。逻辑回归分析显示饮酒是完全缓解的独立预测因素（p = 0.013）。
我们的结果显示习惯性饮酒与较低的CINV发生率有关。酒精摄入对具有ALDH2基因多态性的患者CINV的影响值得进一步研究。
