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Patrizio Lancellotti, Vuyisile T. Nkomo, The intriguing issue of genetic predisposition and the importance of identification of pre-clinical markers of endothelial damage in radiotherapy-induced cardiotoxicity: reply, European Heart Journal - Cardiovascular Imaging, Volume 15, Issue 2, February 2014, Pages 233–234, https://doi.org/10.1093/ehjci/jet248
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We thank Dr Gallucci for her letter about the joint EACVI/ASE expert consensus for multi-modality imaging evaluation of cardiovascular complications of radiotherapy in adults.1 As underlined, there is compelling evidence that chest radiotherapy can increase the risk of heart disease. Although modern radiotherapy techniques are likely to reduce the prevalence and severity of radiation-induced heart disease (RIHD), the incidence of RIHD is expected to increase in cancer survivors who have received old radiotherapy regimens.
The pathophysiology of RIHD remains poorly understood. Genetic and exogenous factors certainly enhance the risk of RIHD and contribute to inter-patient disease expression differences.2 As exogenous factors have been shown to result in genomic instability, and as low-dose radiation induces long-lasting genomic instability, synergistic interaction between radiation-induced effects and pathogenic events unrelated to radiation exposure is highly probable. When normal tissues are irradiated, identifying factors modulating their sensitivity to radiation is paramount but challenging. Little is known about the genetic variants of RIHD. Recently, single-nucleotide polymorphisms in a series of genes associated with DNA repair pathways, damage response, and angiogenesis regulating pathways have been identified. As an example, TGFβ1 29C>T polymorphism, which is associated with a lower TGFβ1 serum level, has been shown to be associated with a two-fold increase in cardiovascular disease risk in breast cancer survivors who were irradiated.3 Although these data are very promising, recommendations on the systematic assessment of these genetic polymorphisms cannot yet be drawn. Also, it would be premature at this time to use these preliminary results to modify the treatment strategies. Further confirmations are needed. However, building a bio-bank of blood samples for further targeted genetic analysis makes sense. Several exogenous factors potentiate the risk of RIHD. Younger age, cardiovascular risk factors (i.e. smoking and hypertension) or pre-existing cardiovascular disease, exposure to high doses of radiation (>30 Gy), concomitant chemotherapy, anterior or left chest irradiation location, and absence of shielding are the most common risk factors associated with RIHD.
