Effect of Bleomycin Hydrolase Gene Polymorphism on Late Pulmonary Complications of Treatment for Hodgkin Lymphoma

PLoS One. 2016 Jun 21;11(6):e0157651. doi: 10.1371/journal.pone.0157651. eCollection 2016.

Abstract

Background: Bleomycin hydrolase (BLMH), an enzyme that inactivates bleomycin, may be a potential candidate that could influence pulmonary function in ABVD (doxorubicin, bleomycin, vinblastin, dacarbasine)-treated Hodgkin lymphoma (HL) patients.

Patients and methods: We hypothesized that the BLMH gene SNP A1450G (rs1050565) influences BLMH activity and late pulmonary toxicity. St. George Respiratory Questionnaire, lung scintigraphy and spirometry were used to determine lung function. TaqMan genotyping assay was used to determine genotype distribution of 131 previously treated HL patients.

Results: Significantly more favorable results were seen in the wild-type A/A genotype group than those in the group containing the mutated allele: A/G+G/G in retrospective pulmonary tests of ABVD treated patients.

Conclusion: Besides limitations of the current study, bleomycin pharmacokinetics should be further evaluated in patients with BLMH variations, hence identify those cases even in the frontline setting, where bleomycin should be omitted and replaced with targeted therapy.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bleomycin / therapeutic use
  • Case-Control Studies
  • Cysteine Endopeptidases / genetics*
  • Dacarbazine / therapeutic use
  • Doxorubicin / therapeutic use
  • Female
  • Gene Frequency / genetics
  • Hodgkin Disease / drug therapy
  • Hodgkin Disease / enzymology*
  • Hodgkin Disease / genetics*
  • Hodgkin Disease / physiopathology
  • Humans
  • Lung / pathology*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Respiratory Function Tests
  • Vinblastine / therapeutic use
  • Young Adult

Substances

  • Bleomycin
  • Vinblastine
  • Dacarbazine
  • Doxorubicin
  • Cysteine Endopeptidases
  • bleomycin hydrolase

Grants and funding

The authors have no support or funding to report.