The Immune Regulator VTCN1 Gene Polymorphisms and Its Impact on Susceptibility to Breast Cancer.
BACKGROUND
VTCN1, a T-cell regulator, belongs to the immunoglobulin superfamily. It is more highly expressed in tumor tissues than in normal tissues, which suggests that it could serve as a tumor-related agent. We hypothesize the gene variants for this coinhibitory molecule may be associated with the risk of breast cancer, given such gene polymorphisms could affect its related gene expression.


METHODS
Genotypes of the VTCN1 gene variants (rs10754339, rs10801935, and rs3738414) were analyzed in 566 patients with breast cancer and 400 age-frequency-matched controls.


RESULTS
Compared with the major allele, the minor alleles of rs10754339, rs10801935, and rs3738414 did modulate the risk of breast cancer with ORs (95% CI) of 1.42 (1.07-1.89), 1.39 (1.10-1.77), and 0.81 (0.67-0.99), respectively. Those with the rs10754339 genotype AG and rs10801935 AC genotype had significantly increased risks when compared with their major genotypes. However, in rs3738414, the AA genotype had a marginally significant decreased risk compared with its wild genotype. In the haplotype-based analysis, the GCG allele was associated with significantly increased risk (OR: 1.56, 95% CI: 1.09-2.22) based on the AAG reference. Further analyses of the haplotype pairs showed GCG carriers had a significantly increased risk.


CONCLUSIONS
In this study, the VTCN1 genetic variants (rs10754339, rs10801935, and rs3738414) indicate they could be connected with the risk of breast cancer, which in turn provides indirect evidence that T-cell immunity could be involved in the development of breast cancer.
Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Shih-Meng
SM
Tsai
Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Surgery, School of Medicine, National Yang Ming University.
Szu-Hsien
SH
Wu
Cancer Center, Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University and Hospital, Kaohsiung, Taiwan.
Ming-Feng
MF
Hou
Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hlio-Han
HH
Yang
Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
Li-Yu
LY
Tsai
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000235:genetics*
D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human
T cells; VTCN1; breast cancer; polymorphisms