Aldehyde dehydrogenase 2 genotype in tolerability of alcohol contained in paclitaxel in Japanese breast cancer patients

Yagi, T.; Fujiishi, Koto; Hasegawa, Akiko; Otsuka, Tomoyuki; Yoshinami, Tetsuhiro; Nishio, Minako; Fujisawa, Fumie; Sugimoto, Naotoshi; Imamura, Fumio

doi:10.1007/s12282-018-0918-9

Cited by 5 publications

(12 citation statements)

References 7 publications

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“…In addition, compared with the previous studies in which the number of breast cancer patients and controls was less than 500 [19][20][21] , the present study has a higher number of patients and 1:3 matching was used to increase the statistical power. In combination with the possible side effects of paclitaxel, a chemotherapeutic agent, due to alcohol's role as a solvent 23 women with the GA/AA genotype of ALDH2 would be highly susceptible to not only breast cancer but also side effects of breast cancer treatment, and are therefore a population with a potentially high risk for delterious health effects.…”

Section: Discussionmentioning

confidence: 99%

Role of aldehyde dehydrogenases, alcohol dehydrogenase 1B genotype, alcohol consumption, and their combination in breast cancer in East-Asian women

Park

Kim

Lee

et al. 2020

Sci Rep

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the associations between genetic polymorphisms in ADH1B (rs1229984) and ALDH2 (rs671), alcohol consumption, the effect of a combination of the two polymorphisms, and breast cancer risk were studied in a population of East-Asian women. In this study, 623 breast cancer cases and 1845 controls, aged 40 or above, were included. The association between ALDH2 polymorphism and breast cancer risk was validated in 2143 breast cancer cases and 3977 controls. Alcohol consumption increased the risk of breast cancer regardless of ADH1B and ALDH2 genotypes. The rs671 polymorphism of ALDH2 was independently associated with increased breast cancer risk (oR = 1.27, 95% CI = 1.02-1.58 per increment of A). The ADH1B rs1229984 polymorphism, and combined effects of the rs671 and rs1229984 polymorphisms, did not reveal any significant association with breast cancer. Stratification by menopausal status revealed that rs671 gene polymorphisms were significantly associated with breast cancer only in postmenopausal women (oR = 1.45, 95% CI = 1.03-2.05 per increment of A). This is the first study to demonstrate an independent association between ALDH2 gene variants and breast cancer in Asian women. further studies are warranted to further elucidate the etiology of breast cancer as it relates to alcohol consumption in Asian women. open Scientific RepoRtS | (2020) 10:6564 | https://doi.population 12 , new studies exploring the associations and interactions among alcohol consumption, related ethanol-metabolizing genes, and breast cancer are warranted. Thus, in the present study, we investigated the association among genetic, functionally established single nucleotide polymorphisms (SNPs) in ADH1B (rs1229984) and ALDH2 (rs671), alcohol consumption, and their combined effects and breast cancer risk in an East-Asian population. Scientific RepoRtS |(2020) 10:6564 | https://doi. Statistical analysis.The relationship between alcohol consumption and breast cancer risk was assessed with a simple logistic regression and a multiple logistic regression adjusted for age at menarche, age at first full term pregnancy, age at menopause, body mass index, smoking status, and rs671/rs1229984 genotype. The relationship between rs671 genotype, rs1229984 genotype, and breast cancer risk was additionally assessed with a simple and a multiple logistic regression adjusted for age at menarche, age at first full term pregnancy, age at menopause, body mass index, smoking status, and alcohol consumption. To assess the association between each SNP and breast cancer, the codominant, dominant, and additive models were considered. In addition, the combined effects of rs671 and rs1229984 genotype on breast cancer were assessed. The ALDH2 and ADH1B genotypes and alcohol intake status were collectively studied to evaluate their combined effect on breast cancer risk. Stratified by ALDH2, ADH1B, and a combination of ALDH2/ADH1B genotypes, the association among alcohol consumption itself, daily alcohol intake, and breast cancer was evaluated with odds ratio (OR) and P-value. In ad...

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Section: Discussionmentioning

confidence: 99%

Role of aldehyde dehydrogenases, alcohol dehydrogenase 1B genotype, alcohol consumption, and their combination in breast cancer in East-Asian women

Park

Kim

Lee

et al. 2020

Sci Rep

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“…13 Another study evaluated paclitaxel infusions in 25 patients with a polymorphism in the gene coding for type 2 aldehyde dehydrogenase ( ALDH2 ): five patients developed grade 1 ethanol-related adverse events. 21 In a crossover study of 24 patients receiving two consecutive administrations of gemcitabine with or without ethanol, the occurrence of acute ethanol-related symptoms was not significantly more frequent in patients receiving ethanol. 8 Finally, Perreault et al 17 retrospectively evaluated the association between the infusion duration of carmustine and the incidence of adverse events during BEAM protocols in two groups of 50 patients receiving a 90- or 120-minute infusion; the incidence of ethanol-related symptoms was similar in the two groups (56% v 52%, respectively; P = .6882).…”

Section: Resultsmentioning

confidence: 96%

“…In the event of a sudden and/or severe reaction to a chemotherapy infusion, the possible presence of ethanol and/or the existence of polymorphisms in the ALDH2 gene should be considered. 21,24 This study's main limitation was the absence of actual clinical data, which prevented us from assessing the clinical impact of ethanol exposure. However, our hypotheses about ethanol exposure are supported by the result of published clinical studies.…”

Section: Discussionmentioning

confidence: 99%

Ethanol Exposure During the Intravenous Administration of Chemotherapeutic Drugs: An Analysis of Clinical Practice and a Literature Review

Hiver¹,

Henry

Vasseur

et al. 2022

JCO Oncology Practice

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PURPOSE: Injectable cytotoxics may be formulated with ethanol. This study sought to quantify the amount of ethanol exposure during chemotherapy infusions. MATERIALS AND METHODS: We first reviewed the antineoplastic drugs (Anatomical Therapeutic and Chemical code L01) and oncologic supportive care drugs (eg, antiemetics) currently available in France, to identify preparations containing ethanol. The amount of ethanol in the final chemotherapy preparation was calculated. Next, we performed a 2-year, single-center, retrospective analysis of injectable antineoplastic drug compounding in routine clinical practice in a French university medical center. Finally, we reviewed our results with regard to the literature data. RESULTS: Ten of the 60 cytotoxic products on the market contained ethanol at concentrations of up to 790 mg/mL, depending on the drug, formulation, and supplier. Several final preparations contained more than 3 g of ethanol per infusion (the maximum recommended by the European Medicines Agency); this was notably the case for gemcitabine, paclitaxel (up to 20 g ethanol per injection, for both), and etoposide (up to 50 g ethanol per infusion). The analysis of our compounding activity showed that 3,172 (4.99%) of the 63,613 chemotherapy preparations (notably paclitaxel) contained more than 3 g of ethanol. None of the oncologic supportive care drugs contained ethanol. CONCLUSION: Patients are exposed to ethanol during the infusion of antineoplastic drugs. With a view to better patient care, physicians and pharmacists should carefully evaluate the risk of ethanol exposure throughout the course of cytotoxic drug treatment.

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“…assumed that individuals with current or former flushing had inactive ALDH2, and found that their responses to a simple flushing questionnaire yielded a sensitivity and specificity of approximately 90% for identifying ALDH2-deficient individuals among the Japanese general population of men and women aged 40 years or older [ 22 – 24 ]. Recently alcohol sensitivity has been reported to be a factor in the side effects of anticancer drugs such as paclitaxel or docetaxel containing alcohol as a solvent [ 25 , 26 ]. The safety of paclitaxel for alcohol intolerance has been studied and patients suspected of alcohol intolerance by a screening question were found to carry inactive genotypes of ALDH2 GA (heterozygous ALDH2 *1/*2 ) or ALDH2 AA (homozygous ALDH2 *2/*2 ) [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recently alcohol sensitivity has been reported to be a factor in the side effects of anticancer drugs such as paclitaxel or docetaxel containing alcohol as a solvent [ 25 , 26 ]. The safety of paclitaxel for alcohol intolerance has been studied and patients suspected of alcohol intolerance by a screening question were found to carry inactive genotypes of ALDH2 GA (heterozygous ALDH2 *1/*2 ) or ALDH2 AA (homozygous ALDH2 *2/*2 ) [ 26 ]. Such chemotherapeutic agents are essential for breast cancer treatment; thus, it is necessary to clarify alcohol sensitivity to protect patients from adverse reactions.…”

Section: Introductionmentioning

confidence: 99%

Influence of alcohol sensitivity on bone metastases and skeletal-related events in primary operable breast cancer: A retrospective cohort study

Tanda

Tada²,

Washio³

et al. 2022

PLoS ONE

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Background Bone metastases in breast cancer patients are a common concern for medical doctors and dentists. Bone-modifying agents, which are necessary to prevent skeletal-related events (SREs), are associated with osteonecrosis of the jaw as an adverse side effect. Hypersensitivity to alcohol is an unfavorable response caused by deficiency of aldehyde dehydrogenase-2 (ALDH2) activity. Inactive ALDH2 is associated with osteoporosis, but its influence on bone metastases is unclear. The aim of our study was to evaluate the effects of alcohol sensitivity on bone metastases and SREs in primary operable breast cancer patients. Methods We retrospectively analyzed patients who were administered docetaxel, an anti-tumor agent, for histologically diagnosed breast cancer between April 2004 and September 2015. Alcohol sensitivity was assessed based on medical records of hypersensitivity to alcohol. The primary endpoint was time to bone metastases and the secondary endpoint was time to first SRE from the initial docetaxel administration. Data were stratified by alcohol sensitivity and tumor stages, and differences were estimated by the Kaplan-Meier method. Prognostic risk factors were analyzed by the multivariate Cox proportional hazards model. Results The median follow-up period of patients with high sensitivity to alcohol (n = 45) was 54 months and that for those with low sensitivity (n = 287) was 64 months. Stratification by alcohol sensitivity revealed that tumor stage exhibited significant correlations with the cumulative incidence of bone metastases in low-sensitivity patients; however, no differences were found in high-sensitivity patients. In multivariate analysis, alcohol sensitivity was a significant prognostic risk factor for bone metastases (HR 2.721, 95% CI 1.268–5.841, P = 0.010). Conclusion Alcohol sensitivity may be a prognostic risk factor for bone metastases. More detailed genetic investigations and metabolic analyses are needed.

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Aldehyde dehydrogenase 2 genotype in tolerability of alcohol contained in paclitaxel in Japanese breast cancer patients

Cited by 5 publications

References 7 publications

Role of aldehyde dehydrogenases, alcohol dehydrogenase 1B genotype, alcohol consumption, and their combination in breast cancer in East-Asian women

Role of aldehyde dehydrogenases, alcohol dehydrogenase 1B genotype, alcohol consumption, and their combination in breast cancer in East-Asian women

Ethanol Exposure During the Intravenous Administration of Chemotherapeutic Drugs: An Analysis of Clinical Practice and a Literature Review

Influence of alcohol sensitivity on bone metastases and skeletal-related events in primary operable breast cancer: A retrospective cohort study

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