Xu Yeqiong, Deng Qiwen, He Bangshun, Pan Yuqin, Li Rui, Gao Tianyi, Sun Huiling, Song Guoqi, Wang Shukui, Cho William C
Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Tumour Biol. 2014 Sep;35(9):9147-61. doi: 10.1007/s13277-014-2175-7. Epub 2014 Jun 12.
This study was designed to reveal the effects of Fas and FasL polymorphisms of interest on breast cancer risk. A total of 439 patients with breast cancer and 439 controls were enrolled in this study. The genotypes Fas -1377G/A, Fas -670A/G, and FasL -844 T/C were detected by MassARRAY. The protein expressions of estrogen receptor, progesterone receptor, and CerbB-2 were determined by immunohistochemistry. Among the 439 patients, Fas mRNA levels in 22 samples of breast cancer and adjacent normal tissues were detected by real-time polymerase chain reaction, and the soluble Fas and Fas ligand concentrations of 180 patients were measured by enzyme-linked immunosorbent assay. The Fas -1377GA, Fas -1377AA, Fas -670AG, Fas -670GG, and FasL -844TC genotypes were associated with a reduced risk of breast cancer. Haplotype analysis indicated that Fas -1377G/-670A was associated with an increased risk of breast cancer, whereas Fas -1377A/-670A was associated with the opposite effect. Furthermore, gene-gene interaction analysis revealed that the Fas -1377GA/AA (-670AG/GG) and FasL -844CC or TC/TT genotypes were associated with a decreased risk of breast cancer. Meanwhile, -1377GG and -670AA genotypes were associated with higher soluble Fas concentrations than other genotypes. We conclude that Fas and FasL polymorphisms can affect breast cancer risk and that Fas polymorphisms are likely to affect breast cancer risk by regulating the soluble Fas concentration.
本研究旨在揭示相关Fas和FasL基因多态性对乳腺癌风险的影响。本研究共纳入439例乳腺癌患者和439例对照。采用MassARRAY检测Fas -1377G/A、Fas -670A/G和FasL -844 T/C基因型。通过免疫组织化学法测定雌激素受体、孕激素受体和CerbB-2的蛋白表达。在439例患者中，采用实时聚合酶链反应检测22例乳腺癌及癌旁正常组织样本中的Fas mRNA水平，采用酶联免疫吸附测定法测定180例患者的可溶性Fas和Fas配体浓度。Fas -1377GA、Fas -1377AA、Fas -670AG、Fas -670GG和FasL -844TC基因型与乳腺癌风险降低相关。单倍型分析表明，Fas -1377G/-670A与乳腺癌风险增加相关，而Fas -1377A/-670A则具有相反的作用。此外，基因-基因相互作用分析显示，Fas -1377GA/AA (-670AG/GG)和FasL -844CC或TC/TT基因型与乳腺癌风险降低相关。同时，-1377GG和-670AA基因型的可溶性Fas浓度高于其他基因型。我们得出结论，Fas和FasL基因多态性可影响乳腺癌风险，且Fas基因多态性可能通过调节可溶性Fas浓度影响乳腺癌风险。
