Wang Wenmin, Zheng Zhongqiu, Yu Wenjie, Lin Hui, Cui Binbin, Cao Feilin
Department of Surgical Oncology, Taizhou Hospital, Wenzhou Medical College, Linhai, Zhejiang 317000, P.R. China.
Oncol Lett. 2012 Mar;3(3):625-628. doi: 10.3892/ol.2011.541. Epub 2011 Dec 28.
FAS and its ligand FASL are crucial in apoptotic cell death. Loss of FAS and gain of aberrant FASL expression are common features of malignant transformation. This study was designed to investigate whether the functional polymorphisms of FAS -1377G/A (rs2234767) and FASL -844T/C (rs763110) affect the risk of developing breast cancer. Genotypes were analyzed by a polymerase chain reaction-restriction fragment length polymorphism assay in 436 breast cancer patients and 496 healthy controls. In this study, as compared to the wild-type homozygote and heterozygote, the distribution of the FAS -1377GG, GA and AA genotypes among breast cancer patients were significantly different from those among healthy controls (P=0.011), with the AA genotype being more prevalent among patients than the controls (P=0.003). Similarly, the frequencies of the FASL -844TT, TC and CC genotypes also significantly differed among breast cancer patients and healthy controls (P<0.001), with the CC genotype being significantly over-represented in breast cancer patients compared with the controls (P<0.001). In the unconditional logistic regression model following adjustment for age, the subjects carrying the FAS -1377AA genotype had a 1.75-fold increased risk [95% confidence interval (CI), 1.13-2.69] for development of breast cancer compared with patients carrying the GG genotype. Similarly, in the recessive model, the FASL -844CC genotype significantly increased the risk of breast cancer with an odds ratio (OR) of 1.92 (95% CI 1.46-2.54) compared with the TT or TT + TC genotypes. Our results suggest that functional polymorphisms in the death pathway genes FAS and FASL significantly contribute to the occurrence of breast cancer.
FAS及其配体FASL在凋亡性细胞死亡中至关重要。FAS缺失和异常FASL表达增加是恶性转化的常见特征。本研究旨在调查FAS -1377G/A（rs2234767）和FASL -844T/C（rs763110）的功能多态性是否会影响患乳腺癌的风险。采用聚合酶链反应-限制性片段长度多态性分析方法对436例乳腺癌患者和496例健康对照者的基因型进行了分析。在本研究中，与野生型纯合子和杂合子相比，乳腺癌患者中FAS -1377GG、GA和AA基因型的分布与健康对照者有显著差异（P = 0.011），AA基因型在患者中的比例高于对照者（P = 0.003）。同样，FASL -844TT、TC和CC基因型的频率在乳腺癌患者和健康对照者中也有显著差异（P < 0.001），与对照者相比，CC基因型在乳腺癌患者中的比例显著过高（P < 0.001）。在对年龄进行校正后的无条件逻辑回归模型中，携带FAS -1377AA基因型的受试者患乳腺癌的风险比携带GG基因型的患者增加了1.75倍[95%置信区间（CI），1.13 - 2.69]。同样，在隐性模型中，与TT或TT + TC基因型相比，FASL -844CC基因型显著增加了患乳腺癌的风险，优势比（OR）为1.92（95% CI 1.46 - 2.54）。我们的结果表明，死亡途径基因FAS和FASL中的功能多态性显著促成了乳腺癌的发生。
