Association of CTLA-4 gene polymorphisms with sporadic breast cancer in Chinese Han population.
BACKGROUND
The host immunogenetic background plays an important role in the development of breast cancer. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a molecule expressed predominantly on activated T cells and is important during the down-regulation of T-cell activation. To evaluate the potential influences of CTLA-4 gene polymorphisms on breast cancer risk, a case-control study was conducted in Han women of Northeast China.


METHODS
We genotyped CTLA-4 variants (-1661 G/A, -658 T/C, -318 T/C, +49 G/A and CT60 G/A) to tag all common haplotypes (>or= 1% frequency) in 117 Chinese breast cancer cases and 148 age/sex matched healthy individuals. Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Data was analyzed using the Chi-square test and Haploview software.


RESULTS
The frequency of CTLA-4 -1661G allele, -318T allele and CT60G allele carriers was significantly higher in patients than in controls (P = 0.0057, OR 1.91, 95% CI 1.21-3.02; P = 0.0031, OR 2.39, 95% CI 1.34-4.27; P = 0.023, OR 1.52, 95% CI 1.06-2.17, respectively). The -658T allele carrier frequency was significantly lower than in controls (P = 0.0000082, OR 0.17, 95% CI 0.08-0.37), whereas the +49A allele was significantly associated with tumor size in patients (P = 0.0033). Two common CTLA-4 haplotypes, ATCGA and ATCAG, were higher in healthy controls than patients (P = 0.0026, OR 0.17, 95% CI 0.05-0.54; P = 0.034, OR 0.12, 95% CI 0.02-0.92, respectively). A strong association was observed between tumor size and the ACCAA, ACCAG and ACCGA haplotypes (P = 0.0032, P = 0.0000031 and P = 0.017).


CONCLUSIONS
These results suggest that polymorphisms of the CTLA-4 gene may modify individual susceptibility to and progression of breast cancer in Chinese Han women.
Wang
Lihong
L
Department of Immunology, Harbin Medical University, Harbin 150081, China. jiangwlh@gmail.com
Li
Dalin
D
Fu
Zhenkun
Z
Li
Heng
H
Jiang
Wei
W
Li
Dianjun
D
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic