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The FAS–FASL system plays crucial role in counterattack of cancer cell against immune system. This study examined the effects ofFAS(−1377G/A and −670A/G) andFASL(−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 cellsex vivoand by analyzing apoptotic tumor-infiltrating lymphocytes (TILs) in breast cancer tissue. We found moderately increased risk associated withFAS−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 withFASL−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 theFASL−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 theFASL−844TT genotype (10.38 ± 4.09% and 24.29 ± 1.50% versus 6.03 ± 0.41% and 17.96 ± 3.66%;P&lt; 0.05 and 0.001). Breast cancer patients with theFASL−844CC genotype had higher apoptotic TILs in their cancer tissues than those with theFASL−844TT genotype (33.7 ± 1.2% versus 19.1 ± 2.0%;P= 0.007). These findings indicate that functional polymorphisms inFASandFASLcontribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer.

carcinogenesis

Functional polymorphisms in               FAS               and               FASL               contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer