Association of CTLA-4 gene polymorphisms with sporadic breast cancer risk and clinical features in Han women of Northeast China

Abstract

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory molecule that plays a pivotal role in downregulating T-cell mediated immune responses. To determine the role of CTLA-4 in tumor immunity, and to validate previous results as well, we investigated four tag single nucleotide polymorphisms (SNPs) of CTLA-4 in a relatively large Chinese Han cohort from northeastern China. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 581 patients and 566 age-matched controls. Our data indicated that compared with the common genotype and allele of each SNP, the -1722 CC genotype and C allele showed an increased risk of breast cancer (P = 0.030, odds ratio (OR) = 1.457, 95% confidence internal (CI) 1.036-2.051; P = 0.024, OR = 1.214, 95% CI 1.026-1.436, respectively). The -1661 GG genotype and G allele were also associated with an increased risk of breast cancer (P = 0.018, OR = 1.396, 95% CI 1.058-1.843; P = 0.013, OR = 1.353, 95% CI 1.066-1.717, respectively). In the haplotype analysis, the CAAA haplotype showed a higher frequency in cases (P = 0.004), and this association remained significant after correcting the P value for multiple testing. Associations were shown between the SNPs of CTLA-4 and lymph node metastasis, estrogen receptor (ER), progesterone receptor (PR) and P53 statuses. These results indicate that some SNPs in the CTLA-4 gene may affect the risk of breast cancer and show that some SNPs are associated with breast cancer characteristics in Han women in northeastern China.

CTLA-4 Gene +49 A/G Polymorphism in Prostate Cancer Patients in Turkish Population

“…Erfani et al 21 identified a relationship between AG genotype and ER expression. Also, Li et al 20 observed a relationship among all CTLA-4 gene polymorphisms with estrogen and progesterone receptors, which was not consistent with our findings.…”

“…According to the results of these studies, the AA genotype was associated with breast cancer, but none of the studied gene polymorphisms was associated with prognostic factors such as tumor stage, grade or size. 8 These results of their studies confirm the findings of two other studies in Iran 7 and China, 20 which found GG genotype is more frequent in breast cancer patients. Erfani et al 21 genotyped 283 patients and 245 healthy control subjects for 21722 T/C, 21661A/G, and 2318C/T single nucleotide polymorphisms in the promoter region of the CTLA4 gene.…”

Association of Five Snps in Cytotoxic T-Lymphocyte Antigen 4 and Cancer Susceptibility: Evidence from 67 Studies

“…Moreover, there were 30 studies with 9675 cases and 9623 controls for rs3087243 [12-15, 17, 23-25, 27-29, 31, 32, 35, 37, 40, 41, 44, 45, 47, 53, 54, 61, 63, 65, 66, 73-75]. Additionally, rs4553808 was in 17 studies [12, 14, 15, 23, 28, 29, 31, 37, 41, 44, 47, 49, 51, 52, 62, 73, 76], rs5742909 was in 32 studies [12, 14, 15, 20, 24, 25, 28-30, 32, 34, 35, 39-41, 45, 47, 52-54, 56, 57, 59, 62, 63, 65, 66, 70, 73, 76, 77], rs733618 was in 14 studies [13, 23, 28, 37, 44, 47, 51, 52, 62, 73-76, 78], and they were analysed. Of the 67 studies, 9 presented a significant deviation from HWE (5 studies on rs231775 [11, 13, 34, 51, 66], 4 studies on rs4553808 [51, 62…”

Evolving Roles for Targeting CTLA-4 in Cancer Immunotherapy

“…More than 100 single nucleotide polymorphisms (SNPs) of CTLA-4 have been identified, for example, rs231775 G>A, rs3087243G>A, rs4553808A>G, rs5742909 C>T, rs733618 A>G, rs16840252 C>T polymorphisms, which play an important role in some autoimmune diseases and cancers [42][43][44]. Recent studies have suggested thatSNPs [+49 (rs231775), CT60 (rs3087243), −1661 (rs4553808), and −318 (rs5742909)] in the promoter region of CTLA-4 gene may modulate the gene expression and are associated with susceptibility to different types of malignances, such as colorectal cancer [45,46], breast cancer [43], hepatocellular carcinoma [47,48], cervical cancer [48][49][50], melanoma [51], head and neck cancer [52], NSCLC [53,54], renal cell carcinoma [55]and others [56] (Fig.…”