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Cytotoxic T lymphocyte antigen-4 promoter variants in breast cancer

      Abstract

      CTLA4 is a coinhibitory molecule expressed mainly on activated T lymphocytes. To test the putative involvement of CTLA-4 in inhibitory state of immunity to breast cancer, we genotyped 283 patients and 245 healthy control subjects for −1722 T/C, −1661 A/G, and −318 C/T single nucleotide polymorphisms in the promoter region of the CTLA4 gene. There were no significant differences in genotype, allele, or haplotype frequencies in all three loci between patients and healthy controls. Moreover, the incidence of the most frequent haplotype combination (TAC/TAC, T −1722, A −1661, C −318) was only slightly higher among healthy controls than patients (68.4 vs. 64.8%, P = 0.2). This haplotype combination was associated with lower stages of the disease (P = 0.0007), however, and higher estrogen receptor (ER) expression in patients (P = 0.006). Association with tumor prognostic or predictive factors was also observed with certain genotypes: the −1661 AA genotype was associated with lesser lymph node (LN) involvement (P = 0.017) and higher ER expression (P = 0.004), and the −318 CC genotype with lesser LN involvement (P = 0.007). These results suggest that CTLA4 promoter variants participate in the progression of breast cancer rather than in its initial development.
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