Polymorphisms of survivin and its protein expression are associated with colorectal cancer susceptibility in Chinese population.

To investigate the association of survivin -31G/C, -141G/C, and -241T/C polymorphisms with colorectal cancer (CRC) susceptibility and explore the mechanisms of the survivin polymorphism in CRC development. A case-control study was conducted of 275 CRC cases and 270 healthy controls. Polymorphisms of survivin -31G/C, -141G/C, and -241T/C were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Survivin and Ki-67 expression was analyzed by immunohistochemistry by the Envision technique for the paraffin sections of 152 CRC. It showed that the -31G/C genotype and allele distribution were significantly different between the CRC cases and controls. The -31CC genotype and -31C allele were over-represented among the CRC cases. Compared with the CC genotype, the GC and GG genotypes had a significantly decreased risk of CRC (p=0.015). Survivin and Ki-67 expression of patients with the CC genotype was significantly higher than the patients with the GC and GG genotypes. In addition, a significantly positive correlation was found between expression of Survivin and Ki-67. There were no significant difference of the -141G/C and -241T/C polymorphism distributions among cases and controls. Survivin 31G/C may adjust the Survivin expression, and it might contribute to a risk of developing CRC.

The influence of functional polymorphisms in matrix metalloproteinase 9 on survival of breast cancer patients in a Chinese population.

Matrix metalloproteinase 9 (MMP9) plays a critical role in cancer aggression, and its overexpression is associated with a poor prognosis in breast cancer. Because common genetic variants can alter the expression or function of MMPs, we hypothesized that potentially functional single-nucleotide polymorphisms (SNPs) in the MMP9 gene may be associated with the survival of patients with invasive breast cancer. In this case-cohort follow-up study, a total of 245 breast cancer patients in southeast China were investigated, and five haplotype tagging SNPs (htSNPs) in the MMP9 gene were genotyped by using matrix-assisted laser desorption/ionization mass spectrometry and polymerase chain reaction-restriction fragment length polymorphism methods. Disease-free survival (DFS) and distance disease-free survival (DDFS) analyses were used to identify the SNPs associated with prognosis and determine their interdependence with the recognized prognostic factors. We found that the MMP9 rs3787268 GA+AA genotypes were significantly associated with poor DFS and DDFS of patients with breast cancer (log-rank p-values 0.045 and 0.028, respectively), especially in some subgroups of patients. Multivariate Cox regression and stepwise COX regression analyses suggested that rs3787268 may be a candidate independent biomarker to predict breast cancer survival in this population. Further, among estrogen receptor (ER)+/epidermal growth receptor 2 (HER-2)- patients, the rs3787268 GA+AA genotypes and rs17577 GG genotype showed a locus-dosage effect between combined the genotypes and decreased survival (adjusted HR 2.59, 95% confidence interval [CI] 1.29-5.19 and adjusted HR 3.25, 95% CI 1.39-7.58, respectively, for DFS and DDFS). Our results suggest that the polymorphisms in the MMP9 gene may be genetic modifiers for breast cancer prognosis in this Chinese population.

The interleukin-6 -147 g/c polymorphism is associated with increased risk of coronary artery disease in young South African Indian men.

BACKGROUND: Interleukin-6 (IL-6) is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases such as coronary artery disease (CAD). The -174 IL-6 G/C promoter polymorphism influences mRNA levels and protein expression and is implicated in CAD. The Indian population in South Africa, unlike the black community, has a high prevalence of premature CAD. This polymorphism has not been fully explored in this population. The present study assessed the -174 IL-6 G/C polymorphism in young Indian patients with angiographically documented CAD and compared them with age- and gender-matched Indian and black control subjects. METHODS: Polymorphic variants were assessed by polymerase chain reaction-restriction fragment length polymorphism, and IL-6 levels were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The -174 IL-6 C allele was found with a higher frequency (23%) in the total Indian group compared to 2% in the black participants [P<0.0001, odds ratio (OR)=0.05, 95% confidence interval (CI) 0.018-0.14). The difference in frequency was more pronounced when Indian controls were compared to black controls (29% vs. 2%, respectively) (P<0.0001, OR=0.05, 95% CI 0.02-0.17). A significant association between the -174 IL-6 G allele and CAD was found in Indian patients compared to Indian controls (84% in cases vs. 71% in Indian controls; P=0.043, OR=0.47 95% CI 0.23-0.95). Levels of IL-6 in circulation were higher in black controls (6.62±0.63 pg/mL) compared to Indian controls (2.51±0.57 pg/mL) and CAD patients (1.46±0.36 pg/mL) (P<0.0001). Levels of IL-6 were higher in all groups with homozygous -174 IL-6 C alleles, but only significant in the healthy Indian control group (GG 3.73±0.94 pg/mL vs. GC/CC 0.89±0.5 pg/mL, P=0.0001). CONCLUSION: The presence of the IL-6 -174 G allele influences levels of IL-6 and increases the risk of CAD in South African Indians.

The vascular endothelial growth factor (VEGF) polymorphisms and the risk of endometriosis in northern Iran.

Vascular endothelial growth factor (VEGF) is known to be a key molecule in the pathogenesis of endometriosis. In this study, we evaluated whether two polymorphisms -460T>C and +405G>C in VEGF are related with the susceptibility to endometriosis in northern Iran. Genomic DNA derived from patients with endometriosis and healthy women were analysed by polymerase chain reaction-restriction fragment length polymorphism. The total number of 1080 subjects (480 patients with endometriosis and 600 normal controls) was enrolled into the study. We used the Chi-square (χ(2)) test to evaluate each allele and genotype frequency of -460T>C and +405G>C polymorphisms among the cases and controls. The associations between the polymorphisms and the risk of endometriosis were estimated by odds ratio and their 95% confidence intervals. There was no significant differences in the VEGF -460T>C genotypes and allele frequencies between control women and endometriosis patients (P = 0.63). In contrast, an increased frequency of the +405CC genotype was observed in the patients with endometriosis as compared with the controls. The +405C allele was associated with the presence of endometriosis. It is concluded that the +405G>C polymorphism in VEGF may be associated with higher risk of endometriosis in northern Iran.

The role of MSP I CYP1A1 gene polymorphism in the development of uterine fibroids.

The cytochrome P-450 1A1 (CYPA1A) gene plays an important role in the metabolization of estrogen and is therefore a candidate marker for fibroids. In a case-control study, we were unable to demonstrate any association between MSP I CYP1A1 polymorphism and the risk of leiomyoma in Brazilian women.

Association of LEP and ADIPOQ common variants with colorectal cancer in Mexican patients.

Leptin and adiponectin are cytokines produced by adipose tissue with opposite effects on tumor growth: the former stimulate whereas the latter inhibit it. The objective was to analyze the association of LEP A19G and ADIPOQ+45 T/G and +276 G/T polymorphisms in Mexican patients with colorectal cancer (CRC). 68 unrelated patients with CRC (study group) and 102 blood donors (control group); all subjects were Mestizos from western Mexico. The polymorphisms were established by PCR-RFLP on DNA samples obtained from peripheral blood. The LEP A19G polymorphism showed significant differences between CRC patients and control group (p= 0.01 for G/A genotype and p= 0.02 for the recessive model G/G +G/A); yet, in the analysis stratified by gender, this difference remained significant only in males. The ADIPOQ polymorphisms did not shown any significant differences. Our results suggest that the A19G LEP polymorphism is associated with CRC in Mexican patients.

Genomic and polyploid evolution in genus Avena as revealed by RFLPs of repeated DNA sequences.

Phylogenetic relationships and genome affinities were investigated by utilizing all the biological Avena species consisting of 11 diploid species (15 accessions), 8 tetraploid species (9 accessions) and 4 hexaploid species (5 accessions). Genomic DNA regions of As120a, avenin, and globulin were amplified by PCR. A total of 130 polymorphic fragments were detected out of 156 fragments generated by digesting the PCR-amplified fragments with 11 restriction enzymes. The number of fragments generated by PCR-amplification followed by digestion with restriction enzymes was almost the same as those among the three repeated DNA sequences. A high level of genetic distance was detected between A. damascena (Ad) and A. canariensis (Ac) genomes, which reflected their different morphology and reproductive isolation. The A. longiglumis (Al) and A. prostrata (Ap) genomes were closely related to the As genome group. The AB genome species formed a cluster with the AsAs genome artificial autotetraploid and the As genome diploids indicating near-autotetraploid origin. The A. macrostachya is an outbreeding autotetraploid closely related with the C genome diploid and the AC genome tetraploid species. The differences of genetic distances estimated from the repeated DNA sequence divergence among the Avena species were consistent with genome divergences and it was possible to compare the genetic intra- and inter-ploidy relationships produced by RFLPs. These results suggested that the PCR-mediated analysis of repeated DNA polymorphism can be used as a tool to examine genomic relationships of polyploidy species.