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Original Article

Association between the cytotoxic T-lymphocyte antigen-4
polymorphisms and breast cancer risk and prognosis

Meraj Farbod , Seyed Mostafa Shiryazdi , Hamid Harazi , Tahereh Nazari , Mohammad Hasan Sheikhha 5
3
4
1
2
1 Department of General Surgery, Shahid Rahnemon Hospital , Shahid Sadoughi University of Medical Sciences, Yazd 8913814396, Iran.
2 Department of General Surgery, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd 8916886938, Iran.
3 Department of General Surgery, Shohada-Kargar Hospital, Social Security Organization, Yazd 8944167699, Iran.
4 Department of Human Genetics, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd 8944157963, Iran.
5 Department of Medical Genetics, Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran.
Correspondence to: Prof. Mohammad Hasan Sheikhha, Department of Medical Genetics, Research and Clinical Center for Infertility, Bolai
Avenue, Safayeh, Yazd 8916877391, Iran. E-mail: sheikhha@yahoo.com

ABSTRACT
Aim: The aim was to evaluate the potential infl uences of cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene polymorphisms on
breast cancer risk, the distribution of CTLA-4 single nucleotide polymorphisms (1661AG) in breast cancer patients and control
subjects was investigated. Methods: In this case-control study, 100 patients with breast cancer as case group and 100 healthy
participants as a control group were compared. Genotypes were determined by the polymerase chain reaction-restriction fragment
length polymorphism method. Demographic characteristics of the study population, as well as tumor size, tumor grade and stage
were collected in a questionnaire designed for this study. The collected data were statistically analyzed by SPSS-16.0 (SPSS Inc.,
Chicago, USA) predictive analytic software using the Chi-square test. Results: The mean age of women was 43.42 ± 13.1 years.
The AA genotype was frequent in case group (43%) whereas the AG genotype was found more in the control group (69%).
There was no signifi cant relationship between the studied polymorphisms and the grade, stage and size of the tumor, nor between
the studied polymorphisms and estrogen receptor, progesterone receptor and lymph node involvement (P > 0.05). Signifi cant
association between the studied polymorphisms and breast cancer metastases was found (P = 0.02). Conclusion: According to the
results of the study, the AA genotype is associated with breast cancer, but none of the studied gene polymorphisms is associated
with prognostic factors such as tumor stage, grade or size.
Key words: Breast cancer, cytotoxic T-lymphocyte antigen-4, polymorphism, prognosis

Introduction innate and adaptive responses, which are frequently
detected in cancer-bearing hosts, remains incompletely
Breast cancer is the most common cancer in women understood. The most considerable antitumor response
[9]
(30% of all cancers among women in developed is made by human cellular immunity mediated by
countries), but is treatable if early diagnosis and treatment T-lymphocyte and natural killer (NK) cells. It follows
occur. The incidence of breast cancer has constantly that variants of genes included in the regulation, and
[1]
[2]
increased since 1940 and based on WHO reports, there proliferation of T-lymphocyte and NK cells would
[3]
is a 2% annual increase in breast cancer prevalence.
There are no exact statistics on the prevalence of breast be effective in predicting the risk of breast cancer.
cancer among the Iranian population (the source of Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is coded
our study); estimates show that Iran has moderate, but by a gene on chromosome 2q33. It is a member of
[4]
increasing, prevalence. Both genetic and environmental the immunoglobulin super family, which transmits an
susceptibilities a re included in breast cancer etiology, [5-8] inhibitory signal to T cells. CTLA-4 binds to B-7 on
but the exact etiology has not been defi nitively identifi ed. antigen-presenting cells, and polymorphism of CTLA-4
Current studies confi rm the role of the immune system on gene interferes with surface activity of B-7, preventing
the etiology of breast cancer. T-lymphocyte from activating. [10,11] In fact, CTLA-4
prevents immune response and its tumor-killing
[12]
It was shown that cancer cells provoke immune activity. CTLA-4 gene is composed of 4 exons and
[13]
recognition, but the biologic importance of antitumor possibly plays a signifi cant role in diseases related to T
cells. More than 100 single-nucleotide polymorphisms
Access this article online are recognized on the CTLA-4 gene. Among them, AG
Quick Response Code: dysmorphisms, located on +49 of exon 1, could make
Website: amino acid (threonine into alanine) on CTLA-4 protein. [14]
www.jcmtjournal.com
Current studies show that this polymorphism affects the
ability of CTLA-4 to bind to B-7 cells and to activate
DOI: [15,16]
10.4103/2394-4722.153314 T cells. These surveys show that translocation of
A allele to G allele on +49 zone decreases the role of
16 Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 1 ¦ April 15, 2015 ¦