Genetic variants in TGFβ-1 and PAI-1 as possible risk factors for cardiovascular disease after radiotherapy for breast cancer.

Abstract

It has been established that radiotherapy can increase cardiovascular disease (CVD) risk. Genetic variants, which play a role in the tissue, damage response and angiogenesis regulating TGFβ pathway might give us insight into the mechanisms underlying radiation-induced CVD. We examined the effects of two polymorphisms, TGFβ1 29C>T and PAI-1 5G>4G, on CVD incidence. This retrospective cohort study included 422 10-year breast cancer survivors, aged <50 years at diagnosis, treated between 1977 and 1995. We collected information on treatment, oncological follow-up, CVD, CVD risk factors and genotypes. During a mean follow-up of 19.4 years, 61 patients developed CVD. Internal mammary chain (IMC) irradiation, exposing a part of the heart to radiation, was associated with a hazard ratio of 2.36 (95% CI: 1.27-4.37, p=0.01) compared to no IMC irradiation. Compared to the C/C+C/T genotype, the T/T genotype of the TGFβ1 polymorphism was associated with hazard ratios of 1.79 (0.99-3.26, p=0.06) and 1.74 (0.90-3.34, p=0.10) in the total and IMC-irradiated group, respectively. We found no evidence for an association between PAI-1 5G>4G and CVD risk. Our study suggests there might be an association between the TGFβ1 29C>T polymorphism and CVD risk in long-term breast cancer survivors.