Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, Netherlands.
Radiother Oncol. 2012 Jan;102(1):115-21. doi: 10.1016/j.radonc.2011.10.017. Epub 2011 Nov 17.
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.
放疗会增加心血管疾病（CVD）的风险，这一点已得到证实。在组织损伤反应和血管生成调节 TGFβ 通路中发挥作用的遗传变异可能会让我们深入了解辐射诱导的 CVD 的潜在机制。我们研究了两种多态性 TGFβ1 29C>T 和 PAI-1 5G>4G 对 CVD 发病的影响。
这项回顾性队列研究纳入了 422 名 10 年乳腺癌幸存者，诊断时年龄<50 岁，1977 年至 1995 年期间接受治疗。我们收集了治疗、肿瘤学随访、CVD、CVD 风险因素和基因型的信息。
在平均 19.4 年的随访期间，61 名患者发生了 CVD。与未进行内乳链（IMC）照射相比，接受 IMC 照射（将部分心脏暴露于辐射中）的患者发生 CVD 的风险比为 2.36（95%CI：1.27-4.37，p=0.01）。与 TGFβ1 多态性的 C/C+C/T 基因型相比，T/T 基因型与总人群和 IMC 照射组的风险比分别为 1.79（95%CI：0.99-3.26，p=0.06）和 1.74（95%CI：0.90-3.34，p=0.10）相关。我们没有发现 PAI-1 5G>4G 与 CVD 风险之间存在关联的证据。
我们的研究表明，TGFβ1 29C>T 多态性与长期乳腺癌幸存者的 CVD 风险之间可能存在关联。
