A gain of function TGFB1 polymorphism may be associated with late stage prostate cancer.
A gain of function TGFB1 polymorphism may be associated with late stage prostate cancer.
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DOI：
10.1158/1055-9965.759.13.5
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发表时间：
2004-05
期刊：
影响因子：
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通讯作者：
Amanda Ewart-Toland;J. Chan;Jinwei Yuan;A. Balmain;Jing Ma
中科院分区：
文献类型：
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作者：
Amanda Ewart-Toland;J. Chan;Jinwei Yuan;A. Balmain;Jing Ma
已知转化生长因子β（TGF β）在肿瘤形成的不同阶段发挥积极和消极作用。在TGF β亚型中，TGF β 1在前列腺癌中高度表达，并导致肿瘤促进和转移。TGF β 1的表达增加与肿瘤更具侵袭性和预后不良相关。已经鉴定了TGFB 1的几种多态性，并且在强连锁不平衡中的两种变体C-509 T和T+29 C显示出增加的血清水平。由于TGFB 1变异体在前列腺癌和进展中的潜在作用，我们假设这两种TGFB 1变异体与前列腺癌风险相关，特别是晚期，更具侵袭性的肿瘤。为了验证这一点，我们对492名来自医生健康研究的前列腺癌患者和492名年龄匹配的对照进行了巢式病例对照研究。在这项研究中，位置-509处T等位基因纯合子的病例发生更晚期前列腺癌的风险增加2.4倍[95%置信区间（95%CI）1.03-5.43; P = 0.04]。T等位基因频率在病例组和对照组分别为32.7%和31.4%。相同的多态性显示总体前列腺癌风险的非显著性比值比（OR）为1.23（95%CI 0.80-1.87）。在+29位点C等位基因纯合子的病例中，总前列腺癌（OR 1.19，95%CI 0.82-1.74）或晚期前列腺癌（OR 1.33，95%CI 0.66-2.68）的风险未显示任何显著增加。C等位基因频率在病例组和对照组分别为39.9%和38.5%。我们的数据表明，TGFB 1 C-509 T变异影响TGF β 1的表达可能在晚期前列腺癌中发挥作用。
Transforming growth factor beta (TGFbeta) is known to exert both positive and negative effects on different stages of tumor formation. Of the TGFbetaisoforms, TGFbeta1 is highly expressed in prostate cancer and leads to tumor promotion and metastasis. Increased expression of TGFbeta1 is associated with more aggressive tumors and poor prognosis. Several polymorphisms in TGFB1 have been identified, and two variants in strong linkage disequilibrium, C-509T and T+29C, show increased serum levels. Because of the potential role of TGFB1 variants in prostate cancer and progression, we hypothesized that these two TGFB1 variants would be associated with prostate cancer risk, particularly later, more aggressive stage tumors. To test this, we conducted a nested case-control study of 492 men diagnosed with prostate cancer from the Physicians Health Study and 492 age-matched controls. In this study, cases who were homozygous for the T allele at position -509 had a 2.4-fold increased risk of more advanced stage of prostate cancer [95% confidence interval (95% CI) 1.03-5.43; P = 0.04]. The T allele frequencies in cases and controls were 32.7% and 31.4%, respectively. The same polymorphism showed a 1.23 nonsignificant odds ratio (OR) for overall prostate cancer risk (95% CI 0.80-1.87). Cases who were homozygous for the C allele at position +29 did not show any significant increase in risk for either total prostate cancer (OR 1.19, 95% CI 0.82-1.74) or advanced stage prostate cancer (OR 1.33, 95% CI 0.66-2.68). The C allele frequency in cases and controls were 39.9% and 38.5%, respectively. Our data suggest that the TGFB1 C-509T variant that affects expression of TGFbeta1 may play a role in advanced stage prostate cancer.