title: Genetic variants in TGFβ-1 and PAI-1 as possible risk factors for cardiovascular disease after radiotherapy for breast cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our study suggests there might be an association between the TGFβ1 29C>T polymorphism and CVD risk in long-term breast cancer survivors.
authors.affiliation: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Florentine S M
authors.initials: FS
authors.lastname: Hilbers
authors.forename: Naomi B
authors.initials: NB
authors.lastname: Boekel
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: van den Broek
authors.forename: Richard
authors.initials: R
authors.lastname: van Hien
authors.forename: Sten
authors.initials: S
authors.lastname: Cornelissen
authors.forename: Berthe M P
authors.initials: BM
authors.lastname: Aleman
authors.forename: Laura J
authors.initials: LJ
authors.lastname: van 't Veer
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
authors.forename: Marjanka K
authors.initials: MK
authors.lastname: Schmidt
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000235:genetics*; D002319:Cardiovascular System / Q000528:radiation effects*; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D053773:Transforming Growth Factor beta1