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.
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References
de Boer-Dennert M, de Wit R, Schmitz PI, Djontono J, Beurden V, Stoter G, et al. Patient perceptions of the side-effects of chemotherapy: the influence of 5HT3 antagonists. Br J Cancer. 1997;76(8):1055–61.
Bloechl-Daum B, Deuson RR, Mavros P, Hansen M, Herrstedt J. Delayed nausea and vomiting continue to reduce patients’ quality of life after highly and moderately emetogenic chemotherapy despite antiemetic treatment. J Clin Oncol. 2006;24(27):4472–8.
Ishiguro H, Nambu Y, Maekawa Y, Adachi S. Evidence-based management of nausea and vomiting. Jpn J Cancer Chemother. 2006;33(5):701–6.
Grunberg SM, Osoba D, Hesketh PJ, Gralla RJ, Borjeson S, Rapoport BL, et al. Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity—an update. Support Care Cancer. 2005;13(2):80–4.
Tremblay P-B, Kaiser R, Sezer O, Rösler N, Schelenz C, Possinger K, et al. Variations in the 5-hydroxytryptamine type 3B receptor gene as predictors of the efficacy of antiemetic treatment in cancer patients. J Clin Oncol. 2003;21(11):2147–55.
Molassiotis A, Stamataki Z, Kontopantelis E. Development and preliminary validation of a risk prediction model for chemotherapy-related nausea and vomiting. Support Care Cancer. 2013;21(10):2759–67.
Hilarius DL, Kloeg PH, van der Wall E, van den Heuvel JJG, Gundy CM, Aaronson NK. Chemotherapy-induced nausea and vomiting in daily clinical practice: a community hospital-based study. Support Care Cancer. 2012;20(1):107–17.
Warr DG, Street JC, Carides AD. Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of phase 3 trial of aprepitant in patients receiving adriamycin–cyclophosphamide-based chemotherapy. Support Care Cancer. 2011;19(6):807–13.
Hesketh PJ, Aapro M, Street JC, Carides AD. Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of two phase III trials of aprepitant in patients receiving cisplatin-based chemotherapy. Support Care Cancer. 2010;18(9):1171–7.
Sekine I, Segawa Y, Kubota K, Saeki T. Risk factors of chemotherapy-induced nausea and vomiting: index for personalized antiemetic prophylaxis. Cancer Sci. 2013;104(6):711–7.
Minami M, Endo T, Hirafuji M. Role of serotonin in emesis. Folia Pharmacol Jpn. 1996;108(5):233–75.
Macgregor S, Lind PA, Bucholz KK, Hansell NK, Madden PAF, Richter MM, et al. Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis. Hum Mol Genet. 2009;18(3):580–93.
Wall TL. Genetic associations of alcohol and aldehyde dehydrogenase with alcohol dependence and their mechanisms of action. Ther Drug Monit. 2005;27(6):700–3.
Enomoto N, Takase S, Yasuhara M, Takada A. Acetaldehyde metabolism in different aldehyde dehydrogenase-2 genotypes. Alcohol Clin Exp Res. 1991;15(1):141–4.
Higuchi S, Muramatsu T, Matsushita S, Murayama M, Hayashida M. Polymorphisms of ethanol-oxidizing enzymes in alcoholics with inactive ALDH2. Hum Genet. 1996;97(4):431–4.
Mitani Y, Lezhava A, Kawai Y, Kikuchi T, Oguchi-Katayama A, Kogo Y, et al. Rapid SNP diagnostics using asymmetric isothermal amplification and a new mismatch-suppression technology. Nat Meth. 2007;4(3):257–62.
Dockham PA, Lee M-O, Sladek NE. Identification of human liver aldehyde dehydrogenases that catalyze the oxidation of aldophosphamide and retinaldehyde. Biochem Pharmacol. 1992;43(11):2453–69.
LE Rikans. The oxidation of acrolein by rat liver aldehyde dehydrogenases. relation to allyl alcohol hepatotoxicity. Drug Metab Disposition. 1987;15(3):356–62.
Helander A, Walzer C, Beck O, Balant L, Borg S, von Wartburg J. Influence of genetic variation in alcohol and aldehyde dehydrogenase on serotonin metabolism. Life Sci. 1994;55(5):359–66.
Doorn JA, Florang VR, Schamp JH, Vanle BC. Aldehyde dehydrogenase inhibition generates a reactive dopamine metabolite autotoxic to dopamine neurons. Parkinsonism Relat Disord. 2014;20(Supplement 1):S73–5.
Acknowledgements
We appreciate all participants and their families, as well as staff members of the Department of Breast Oncology. We also thank Takako Ikegami and Tomomi Ikeda from the Laboratory of Molecular and Biochemical Research for their helpful technical advice and Dr. Bierta Barfod for editing our manuscript.
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Uomori, T., Horimoto, Y., Mogushi, K. et al. Relationship between alcohol metabolism and chemotherapy-induced emetic events in breast cancer patients. Breast Cancer 24, 702–707 (2017). https://doi.org/10.1007/s12282-017-0761-4
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DOI: https://doi.org/10.1007/s12282-017-0761-4