Toll-like receptor 5 gene polymorphism is associated with breast cancer susceptibility.

Toll-like receptor 5 (TLR5) plays a fundamental role in immune responses. Recent findings suggest the TLR5 expression level affects cancer progression and development. In the present study, our examination of 256 breast carcinomas specimens revealed that TLR5 is overexpressed in breast carcinomas, and that TLR5 overexpression correlated with lymph node metastasis and cancer grade (p<0.01). In a case-control study, we also analyzed associations between TLR5 single nucleotide polymorphisms (SNPs) and breast cancer risk. Compared were 516 Chinese Han women diagnosed mainly with infiltrative ductal carcinoma and 520 age-matched healthy controls. The nonsense SNP rs5744168 causes truncation of the TLR5 transmembrane signaling domain and was associated with breast cancer risk (p<0.05). However, no statistical association was detected between SNP rs5744168 and any of the clinical parameters tested. Our findings thus indicate that TLR5 SNP rs5744168 is associated with sporadic breast cancer occurrence.

SNP-SNP interactions of immunity related genes involved in the CD28/B7 pathway with susceptibility to invasive ductal carcinoma of the breast.

To explore the interactions among immunity related genes and the risk of breast cancer (BC), 376 invasive ductal carcinoma (IDC) of the breast cases and 366 healthy controls were selected into our study. Twenty single nucleotide polymorphisms (SNPs) of five immunological genes in the CD28/B7 pathway were genotyped. Overall, five SNPs filtered by the Relief F algorithm were rs733618, rs11889031, rs4553808, rs4675374 and rs10754339. The best model of multifactor dimensionality reduction (MDR) contained rs733618 and rs11889031. The high risk genotype combination contributed to increasing risk of breast cancer (odds ratio (OR), 4.36; 95% confidence interval (CI); 3.15-6.02). The information gain (IG) value of these two SNPs was 8.07%, presented the strongest interaction effect. Five significant multiplicative interactions and seven significant combining effects were found among the filtered SNPs. Moreover, the filtered SNPs were still stable in the groups of ER(+), PR(+), CerbB2(-) and lymph node (LN) involvement positive with the best models including rs733618 and rs11889031. The most frequent haplotype was TACC which significantly increased breast cancer risk (OR, 1.80; 95% CI, 1.43-2.25). These results suggested that interactions among cytotoxic T lymphocyte antigen-4 (CTLA4), inducible co-stimulator (ICOS) and B7H4 might play critical roles on the risk of breast cancer.

Reviews on association between the inhibitory costimulatory molecules B7 -H4 and female malignant tumor / 实用肿瘤学杂志

The new costimulatory molecule B7-H4,also called V-set domain containing T cell activa-tion inhibitor 1(VTCN-1),is a member of the B7 family.B7-H4 can negatively regulate the immune response of T lymphocytes through inhibiting their proliferation and cytokine production .The expression of B7-H4 plays an important role in initiation ,progression and regression of malignant tumors ,including female malignant tumor , such as breast cancer ,ovarian cancer and uterine neoplasm .The association between the female tumors and B 7-H4 causes great concern in recent years .In this review,the function of B7-H4 in female tumor research and the potential target of B7-H4 in the diagnosis and treatment of female tumor are summarized .

Association of OX40L polymorphisms with sporadic breast cancer in northeast Chinese Han population.

OX40L is an important costimulatory molecule that plays a crucial role in the regulation of T-cell-mediated immunity. The interaction of OX40-OX40L is involved in the pathogenesis of multiple autoimmune and inflammatory diseases such as systemic lupus erythematosus (SLE), carotid artery disease and cancer. The genetic variants of OX40L can increase the risk of SLE, atherosclerosis, systemic sclerosis and show gender-specific effects in some studies. Accordingly, we performed a case-control study including 557 breast cancer patients and 580 age- and sex-matched healthy controls to investigate whether single nucleotide polymorphisms (SNPs) in the OX40L gene are associated with sporadic breast cancer susceptibility and progression in Chinese Han women. Seven SNPs of OX40L (rs6661173, rs1234313, rs3850641, rs1234315, rs12039904, rs844648 and rs10912580) were genotyped with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results indicated that rs3850641G allele could increase the susceptibility to breast cancer (P = 0.009662), even in the validation study (P = 0.0001515). A significant association between rs3850641 and breast cancer risk was observed under the additive model and dominant model (P = 0.01042 and 0.01942, respectively). The haplotype analysis showed that haplotype A(rs844648)A(rs10912580) was significantly associated with breast cancer, even after 10,000 permutations for haplotypes in block only (P = 0.0003). In clinicopathologic features analysis, the association between rs1234315 and C-erbB2 status was significant (P = 0.02541). Our data primarily indicates that rs3850641 of OX40L gene contributes to sporadic breast carcinogenesis in a northeast Chinese Han population.

Association of CD40 gene polymorphisms with sporadic breast cancer in Chinese Han women of Northeast China.

BACKGROUND: Breast cancer is a polygenetic disorder with a complex inheritance pattern. Single nucleotide polymorphisms (SNPs), the most common genetic variations, influence not only phenotypic traits, but also interindividual predisposition to disease, treatment outcomes with drugs and disease prognosis. The co-stimulatory molecule CD40 plays a prominent role in immune regulation and homeostasis. Accumulating evidence suggests that CD40 contributes to the pathogenesis of cancer. Here, we set out to test the association between polymorphisms in the CD40 gene and breast carcinogenesis and tumor pathology. METHODOLOGY AND PRINCIPAL FINDINGS: Four SNPs (rs1800686, rs1883832, rs4810485 and rs3765459) were genotyped by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method in a case-control study including 591 breast cancer patients and 600 age-matched healthy controls. Differences in the genotypic distribution between breast cancer patients and healthy controls were analyzed by the Chi-square test for trends. Our preliminary data showed a statistically significant association between the four CD40 gene SNPs and sporadic breast cancer risk (additive P = 0.0223, 0.0012, 0.0013 and 0.0279, respectively). A strong association was also found using the dominant, recessive and homozygote comparison genetic models. In the clinical features analysis, significant associations were observed between CD40 SNPs and lymph node metastasis, human epidermal growth factor receptor 2 (C-erbB2), estrogen receptor (ER), progesterone receptor (PR) and tumor protein 53 (P53) statuses. In addition, our haplotype analysis indicated that the haplotype C(rs1883832)G(rs4810485), which was located within the only linkage disequilibrium (LD) block identified, was a protective haplotype for breast cancer, whereas T(rs1883832)T(rs4810485) increased the risk in the studied population, even after correcting the P value for multiple testing (P = 0.0337 and 0.0430, respectively). CONCLUSIONS AND SIGNIFICANCE: Our findings primarily show that CD40 gene polymorphisms contribute to sporadic breast cancer risk and have a significant association with clinicopathological features among Chinese Han women from the Heilongjiang Province.

Association of DNMT1 gene polymorphisms in exons with sporadic infiltrating ductal breast carcinoma among Chinese Han women in the Heilongjiang Province.

BACKGROUND: Infiltrating ductal carcinoma (IDC) is the most common malignant breast cancer in women, and genetic factors appear to play a significant role in the susceptibility to IDC. Alteration of DNA methylation is an epigenetic change in human cancers, including breast cancer. DNA-methyltransferase 1 (DNMT1) is a major enzyme that determines genomic methylation patterns. In order to clarify the association of DNMT1 polymorphisms with IDC, a case-control study was conducted in women from the Heilongjiang Province, in the northeast of China. PATIENTS AND METHODS: We scrutinized the 2 genetic polymorphisms in exons of DNMT1 that may influence the activity of DNMT1. Our research subjects consisted of 305 patients with IDC and 314 age-matched healthy controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Data were analyzed using the χ2 test by SPSS, version 13.0, and Haploview, version 4.1. The association between DNMT1 polymorphisms and the clinical features of IDC was analyzed. RESULTS: In rs16999593, the frequency of CT genotype and C allele were lower in patients than in controls (P = .028 and P = .017, respectively). Also, rs2228611 AG genotype was higher in patients than in controls (P = .015). The frequency of haplotype CA was lower in patients than in controls (P = .034). Significant association was shown between the 2 single nucleotide polymorphisms of the DNMT1 gene and progesterone receptor (PgR) and p53 status. No association was found between DNMT1 gene polymorphisms and tumor size or estrogen receptor status. CONCLUSION: Our results was a previous study, which suggested that DNMT1 gene polymorphisms in exons may provide valuable information for predicting the sporadic IDC risk and may be associated with prognosis factors such as PgR and p53 status in Chinese Han women in the Heilongjiang Province.

Association between polymorphisms of B7-H4 gene and the risk of sporadic breast cancer in Heilongjiang Province / 肿瘤研究与临床

Objective To evaluate the association between the polymorphisms of BT-H4 gene and the risk of breast cancer, a case-control study was conducted in the population of Heilongjiang province, China. Methods We genotyped the single nucleotide polymorphisms of rs10754339, rs10801935 and rs3738414 in B7-H4 gene by PCR-RFLP in a Chinese population consisting of 287 breast cancer cases and 305 controls matched for age and sex, tagged all common haplotypes (frequency ≥ 1%), and analyzed the differences between patients and normal controls. Results Our data indicated that in rs10754339, the frequencies of G allele, AA genotype and AG genotype were significantly different between patients and controls (P=0.030, OR 1.359, 95 % CI 1.030-1.794; P=0.018, OR 0.671, 95 % CI 0.482-0.935; P=0.029, OR 1.455, 95 % CI 1.038-2.038, respectively). In rs3738414, the frequencies of A allele, GG genotype and AG genotype were significantly different between patients and controls (P=0.0008, OR 0.604, 95 % CI 0.455-0.803; P=0.001, OR 1.804, 95 % CI 1.289-2.253; P=0.005, OR 0.612, 95 % CI 0.435-0.862). The frequencies of AAA haplotype and GAG haplotype were significantly different between patients and controls (P=0.0015, OR 0.614, 95 % CI 0.456-0.828; P=0.0003, OR 1.954, 95 % CI 1.363-2.803). Conclusion Polymorphisms of B7-H4 gene appear to be associated with breast cancer in the population of Heilongjiang province, China.

Study on Inhabition Effect of Chitlsan Oligosaccharide on Tumour / 医学研究杂志

Objective To observe the inhibition effect of chitlsan oligosaccharide on tumour. Methods The growth of tumour were observed after chitlsan oligosaccharide was injected into abdominal cavity(ip) or introtumour of mice;And the anti proliferation activities of chitlsan oligosaccharide on cells were evaluated by means of MTT assay. Results Growth of tumour were inhibited by chitlsan oligosaccharide, necrosis was observed in the tumour tissue.Chitlsan oligosaccharide affected the growth of cell. The effect was related to concentration of chitlsan oligosaccharide,but not depending of culture time.The apoptosis of cells could be seen under the transmission electron.Conclusion Chitlsan oligosaccharide could inhibit the growth of tumour and might induce apoptosis of cell.