Functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer
Functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer
复制标题
FAS 和 FASL 的功能多态性导致肿瘤浸润淋巴细胞凋亡增加和乳腺癌风险增加
DOI：
10.1093/carcin/bgl250
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发表时间：
2007-05-01
期刊：
影响因子：
4.7
通讯作者：
Lin, Dongxin
中科院分区：
文献类型：
--
作者：
Zhang, Bailin;Sun, Tong;Lin, Dongxin
Fas-FASL系统在癌细胞对免疫系统的反击中起重要作用。本研究探讨Fas(-1377G/A和-670A/G)和FASL(-844T/C和7896G/C)基因多态性对乳腺癌风险和T淋巴细胞凋亡的影响。通过对840名患者和840名对照的病例对照分析，确定其对乳腺癌风险的影响。通过体外T细胞活化诱导细胞死亡(AICD)和分析乳腺癌组织中肿瘤浸润性淋巴细胞(TIL)的凋亡来确定其对T淋巴细胞凋亡的影响。我们发现与Fas-1377AG[优势比(OR)，1.29；95%可信区间(CI)，1.05-1.59]和-1377AA(OR，1.36；95%CI，1.01-1.82)基因携带者相比，FASL-844CT(OR，0.76；95%CI，0.62-0.94)和-844TT(OR，0.66；95%CI，0.43-1.00)基因携带者风险中等增加。与FASL-844TTT型相比，携带FASL-844CC型的T淋巴细胞FASL表达增加(10.38+/-4.09%和24.29+/-1.50%vs6.03+/-0.41%和17.96+/-3.66%；P<；0.05和0.001)。携带FASL-844CC基因的乳腺癌患者癌组织中的TIL凋亡率明显高于携带FASL-844TT基因的乳腺癌患者(33.7%+/-1.2%vs19.1+/-2.0%；P=0.007)。这些结果表明，Fas和FASL的功能多态性增加了肿瘤浸润性淋巴细胞的凋亡率，增加了乳腺癌的风险。
The FAS-FASL system plays crucial role in counterattack of cancer cell against immune system. This study examined the effects of FAS (-1377G/A and -670A/G) and FASL (-844T/C and 7896G/C) polymorphisms on breast cancer risk and apoptosis of T lymphocytes. The effect on breast cancer risk was determined by case-control analysis of 840 patients and 840 controls. The effects on T-lymphocyte apoptosis were determined by activation-induced cell death (AICD) of T cells ex vivo and by analyzing apoptotic tumor-infiltrating lymphocytes (TILs) in breast cancer tissue. We found moderately increased risk associated with FAS -1377AG [odds ratio (OR), 1.29; 95% confidence interval (CI), 1.05-1.59] and -1377AA (OR, 1.36; 95% CI, 1.01-1.82) genotypes compared with the -1377GG genotype and decreased risk associated with FASL -844CT (OR, 0.76; 95% CI, 0.62-0.94) and -844TT (OR, 0.66; 95% CI, 0.43-1.00) genotypes compared with the -844CC genotype. T lymphocytes with the FASL -844CC genotype had heightened FASL expression that is associated with increased AICD of the T cells stimulated by MCF-7 cells or phytohemagglutinin compared with the FASL -844TT genotype (10.38 +/- 4.09% and 24.29 +/- 1.50% versus 6.03 +/- 0.41% and 17.96 +/- 3.66%; P < 0.05 and 0.001). Breast cancer patients with the FASL -844CC genotype had higher apoptotic TILs in their cancer tissues than those with the FASL -844TT genotype (33.7 +/- 1.2% versus 19.1 +/- 2.0%; P = 0.007). These findings indicate that functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer.