title: Functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer.
abstract: 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.
authors.affiliation: Center of Breast Diseases and Department of Abdominal Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Bailin
authors.initials: B
authors.lastname: Zhang
authors.forename: Tong
authors.initials: T
authors.lastname: Sun
authors.forename: Liyan
authors.initials: L
authors.lastname: Xue
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Han
authors.forename: Baoning
authors.initials: B
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.forename: Yuankai
authors.initials: Y
authors.lastname: Shi
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Yongli
authors.initials: Y
authors.lastname: Guo
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
mesh_terms: D000328:Adult; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D053222:Fas Ligand Protein / Q000235:genetics*; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics*
chemical_list: D053222:Fas Ligand Protein; D019014:fas Receptor