Polymorphisms and radiotherapy

adiotherapy is commonly applied after breast-conserving surgery to reduce the risk of loco-regional recurrence of breast cancer, however patients vary considerably in their normal tissue responses to radiotherapy. Inter-individual variability in radiosensitivity is a multifactorial trait which is known to depend not only on treatment parameters such as the total dose, the dose per fraction, and the treatment volume but also on patient-related factors. Although several lines of evidence support a genetic basis for radiosensitivity, the specific genetic determinants and the underlying molecular mechanisms are only partly understood.

Aim of our ongoing study is to identify genetic variations predictive of acute and late normal tissue toxicity in patients submitted to post-surgical radiotherapy for breast cancer. The identification of relevant gene variants could contribute to the construction of predictive risk models for the occurrence of radiation-induced toxicities in breast cancer patients that could permit the identification of patients who are at increased risk of developing severe side effects. In addition, patients at reduced risk of side effects could be identified allowing dose escalation to enhance the probability of tumor cure leading to an individualization of radiotherapy.


Project leaders: Armando Genazzani, Salvatore Terrazzino.

Clinical Centers: Prof. M. Krengli (Ospedale “Maggiore della Carità”, Novara).


Publications

Terrazzino S, Deantonio L, Cargnin S, Donis L, Pisani C, Masini L, Gambaro G, Canonico PL, Genazzani AA, Krengli M. DNA Methyltransferase Gene Polymorphisms for Prediction of Radiation-induced Skin Fibrosis after Treatment of Breast Cancer: a Multifactorial Genetic Approach. Cancer Res Treat. 2017 Apr;49(2):464-472.

Terrazzino S, Deantonio L, Cargnin S, Donis L, Pisani C, Masini L, Gambaro G, Canonico PL, Genazzani AA, Krengli M. Common European mitochondrial haplogroups in the risk for radiation-induced subcutaneous fibrosis in breast cancer patients. Clinical Oncology 2016,28:365-372

Terrazzino S, Mattina PL, Masini L, Caltavuturo T, Gambaro G, Canonico PL, Genazzani AA, Krengli M. Common variants of eNOS and XRCC1 genes may predict acute skin toxicity in breast cancer patients receiving radiotherapy after breast conserving surgery. Radiother Oncol. 2012;103:199-205.

Terrazzino S, La Mattina P, Gambaro G, Masini L, Franco P, Canonico PL, Genazzani AA, Krengli M. Common Variants of GSTP1, GSTA1, and TGFβ1 are Associated With the Risk of Radiation-Induced Fibrosis in Breast Cancer Patients. Int J Radiat Oncol Biol Phys. 2012;83:504-11.