Highlights
- •Variants in the HFE gene, H63D and C282Y, lead to accumulation of extracellular iron in lungs.
- •Iron handling may play a role in development of bleomycin- and cisplatin-induced toxicity.
- •The H63D variant is associated with a higher prevalence of bleomycin-induced pulmonary toxicity.
Abstract
Background
Bleomycin and cisplatin are of key importance in testicular cancer treatment. Known
potential serious adverse effects are bleomycin-induced pulmonary toxicity (BIP) and
cisplatin-induced renal toxicity. Iron handling may play a role in development of
this toxicity. Carriage of allelic variants of the HFE gene induces altered iron metabolism and may contribute to toxicity. We investigated
the association between two common allelic variants of the HFE gene, H63D and C282Y, with development of pulmonary and renal toxicity during and
after treatment with bleomycin- and cisplatin-containing chemotherapy.
Methods
In 369 testicular cancer patients treated with bleomycin and cisplatin at the University
Medical Center Groningen between 1978 and 2006, H63D and/or C282Y genotypes were determined
with an allelic discrimination assay. Data were collected on development of BIP, pulmonary
function parameters, renal function, and survival.
Results
BIP developed more frequently in patients who were heterozygote (16 in 75, 21%) and
homozygote (2 in 4, 50%) for the H63D variant, compared with those who had the HFE wild-type gene (31 in 278, 11%) (p = 0.012). Overall survival, testicular cancer-related
survival, and change in renal function were not associated with the H63D variant.
Conclusion
We observed an association between presence of one or both H63D alleles and development
of BIP in testicular cancer patients treated with bleomycin combination chemotherapy.
In patients heterozygote and homozygote for the H63D variant, BIP occurred more frequently
compared with wild-type patients. When validated and confirmed, HFE H63D genotyping may be used to identify patients with increased risk for pulmonary
bleomycin toxicity.
Keywords
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Article info
Publication history
Published online: March 28, 2016
Accepted:
February 13,
2016
Received in revised form:
January 5,
2016
Received:
September 30,
2015
Identification
Copyright
© 2016 Elsevier Ltd. All rights reserved.
