title: Relationship between alcohol metabolism and chemotherapy-induced emetic events in breast cancer patients.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  The wild type (ALDH2*1/*1), heterozygote (ALDH2*1/*2), and mutant homozygote (ALDH2*2/*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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan. tuomori@juntendo.ac.jp.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Uomori
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Horimoto
authors.affiliation: Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mogushi
authors.affiliation: Clinical Research Support Center, Juntendo University School of Medicine, 3-1-3 Bunkyo-ku, Hongo, Tokyo, Japan.
authors.forename: Joe
authors.initials: J
authors.lastname: Matsuoka
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Mitsue
authors.initials: M
authors.lastname: Saito
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D011788:Quality of Life; D014839:Vomiting / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000431:Ethanol; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial
keywords: ALDH2; Breast cancer; CINV