The association between three AXIN2 variants and cancer risk.

Plenty of epidemiological studies have assessed the effects of AXIN2 polymorphisms on the risk of developing cancer, but the available results were somewhat inconclusive. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to investigate the relationship between three AXIN2 variants (rs2240308 C/T, rs1133683 C/T, and rs4791171 A/G) and overall cancer susceptibility. In silico tools were undertaken to investigate the correlation of AXIN2 expression with cancer risk and survival time. Furthermore, we explored the serum expression of AXIN2 by enzyme-linked immunosorbent assay. A total of 4167 cancer patients and 3515 control subjects were evaluated. The overall results demonstrated that there was no major association of these polymorphisms on cancer risk. However, stratified analysis by cancer type showed evidence that rs2240308 C/T polymorphism had a lower risk in lung cancer (OR, 0.76; 95% CI, 0.63-0.92; Pheterogeneity = 0.865) and prostate cancer (OR, 0.54; 95% CI, 0.35-0.84; Pheterogeneity = 0.088) by heterozygote comparison. Similar results were indicated in Asian descendants and population-based studies. In silico analysis showed evidence that AXIN2 expressions in lung cancer and prostate cancer were lower than that in normal counterpart. High expression of AXIN2 may have longer overall survival time than low expression group for lung cancer participants. In addition, individuals who were CC/TC carriers had a higher serum expression level than TT carriers. In conclusion, this pooled analysis suggested that AXIN2 rs2240308 C/T variant may decrease both lung and prostate cancer susceptibility, particularly in Asian descendants and population-based studies. Future large scale and well-designed research are required to validate these effects in more detail.

Association between IL8RB C1208T mutation and risk of cancer: A pooled analysis based on 5299 cases and 6899 controls.

INTRODUCTION: The CXC chemokines are unique cytokines that play a vital role in the progression of many cancers. Association between chemokine (C-X-C motif) receptor 2 (IL8RB) C1208T mutation and cancer risk remains incomprehensive. METHODS: We therefore utilized odds ratios and in silico analysis to explore the relationship of IL8RB polymorphism on risk to cancer. Furthermore, we adopted gene set enrichment analysis to investigate the IL8RB expression in prostate adenocarcinoma. RESULTS: A total of 14 case-control studies combined with 5299 cases and 6899 controls were included in our analysis. We revealed that individuals carrying TT genotype had an 14% increased cancer risk compared with those with TC + colon cancer (CC) genotype (odds ratio [OR] = 1.14, 95% CI = 1.05-1.25, P = .003, I2 = 35.6). Stratification analysis by race showed that East Asians with TT + TC genotype may have a 25% decreased cancer risk compared with control. Stratification analysis by cancer type revealed that individuals with TT genotype were associated with elevated risk of urinary cancer than control. The expression of IL8RB was attenuated in prostate adenocarcinoma. CONCLUSIONS: IL8RB C1208T may be correlated with the risk of cancer, especially prostate adenocarcinoma.

[Expressions of interleukin-15 and osteopontin mRNA in early stage of acute rejection of renal allograft in rats].

OBJECTIVE: To study the expressions of interleukin-15 (IL-15), osteopontin (OPN), granzyme B (GraB) and perforin (PFP) mRNA in early stage of acute rejection (AR) of renal allograft in rats. METHODS: The rat renal transplantation model was established. Male Brown Norway and Lewis rats were used as donors and recipients. Four groups were designated: CsA group (BN-->LEW, n = 10, recipients were treated with CsA i.p.); AB group (BN-->LEW, n = 10, recipients were treated with anti-IL-15 neutralizing antibody i.p.); AR group (BN-->LEW, n = 10, recipients were treated with normal saline i.p.) and control group (LEW-->LEW, n = 6, recipients were treated with normal saline i.p.). The blood samples of recipients were drawn at Days 1, 3, 5 and 7 post-transplantation. The serum expressions of IL-15, OPN, PFP and GraB mRNA of recipients were detected by real-time PCR. Allograft tissues were analyzed by pathological assays. RESULTS: In comparison with other groups, the expressions of OPN, IL-15, PFP and GraB mRNA in AR group were gradually up-regulated and peaked at Day 5. The expressions of IL-15 mRNA in CsA and AB groups were 9685 +/- 1440 and 4346 +/- 741 respectively at Day 5 post-operation. It was significantly lower than that in AR group (17 022 +/- 2153, P < 0.01). The expression of IL-15 mRNA in AB group was significantly lower than that in CsA group (P < 0.01). The expressions of OPN mRNA in CsA and AB groups (13 226 +/- 1565 vs 19 112 +/- 2908) were both significantly lower than that in AR group (24 663 +/- 2449, P < 0.01). But the expression of OPN mRNA in AB group was higher than that in CsA group (P < 0.01). At Day 5 post-transplantation, both the expressions of PFP and GraB mRNA in AB and CsA groups was lower than that in AR group (P < 0.01). The pathological results showed that severe AR occurred at Day 7 post-transplantation in AR group and whereas the extent of rejection sign relieved in AB group. CONCLUSION: In early stage of AR of renal allograft in rats, the expressions of OPN, IL-15, PFP and GraB mRNA are up-regulated. Blocking IL-15/IL-15R pathway in early stage of AR can down-regulate the expressions of PFP and GraB mRNA.