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http://hdl.handle.net/1956/2683
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| Tittel: | Association between long-term neuro-toxicities in testicular cancer survivors and polymorphisms in glutathione-s-transferase-P1 and -M1, a retrospective cross sectional study |
| Forfattere: | Oldenburg, Jan
Kraggerud, Sigrid M.
Brydøy, Marianne
Cvancarova, Milada
Lothe, Ragnhild A.
Fossa, Sophie D. |
| Dato: | 27-Dec-2007 |
| Forlag: | BioMed Central |
| Sitering: | Journal of Translational Medicine 2007, 5:70 |
| Sammendrag: | Background: To assess the impact of polymorphisms in Glutathione S-transferase (GST) -P1, -
M1, and -T1 on self-reported chemotherapy-induced long-term toxicities in testicular cancer
survivors (TCSs).
Methods: A total of 238 TCSs, who had received cisplatin-based chemotherapy at median twelve
years earlier, had participated in a long-term follow-up survey which assessed the prevalence of
self-reported paresthesias in fingers/toes, Raynaud-like phenomena in fingers/toes, tinnitus, and
hearing impairment. From all TCSs lymphocyte-derived DNA was analyzed for the functional A→G
polymorphism at bp 304 in GSTP1, and deletions in GST-M1 and GST-T1. Evaluation of associations
between GST polymorphisms and self-reported toxicities included adjustment for prior treatment.
Results: All six evaluated toxicities were significantly associated with the cumulative dose of
cisplatin and/or bleomycin. Compared to TCSs with either GSTP1-AG or GSTP1-AA, the 37 TCSs
with the genotype GSTP1-GG, were significantly less bothered by paresthesias in fingers and toes (p
= 0.039, OR 0.46 [0.22–0.96] and p = 0.023, OR 0.42 [0.20–0.88], respectively), and tinnitus (p =
0.008, OR 0.33 [0.14–0.74]). Furthermore, absence of functional GSTM1 protected against hearing
impairment (p = 0.025, OR 1.81 [1.08–3.03]).
Conclusion: In TCSs long-term self-reported chemotherapy-induced toxicities are associated
with functional polymorphisms in GSTP1 and GSTM1. Hypothetically, absence of GST-M1 leaves
more glutathione as substrate for the co-expressed GST-P1. Also intracellular inactivation of proapoptotic
mediators represents a possible explanation of our findings. Genotyping of these GSTs
might be a welcomed step towards a more individualized treatment of patients with metastatic
testicular cancer. |
| URI: | http://dx.doi.org/10.1186/1479-5876-5-70
http://hdl.handle.net/1956/2683 |
| Vises i samlingene: | Section for Oncology
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