The association of interleukin-16 polymorphisms with IL-16 serum levels and risk of colorectal and gastric cancer

Interleukin (IL)-16, a multifunctional cytokine, plays a fundamentalrole in inflammatory diseases, as well as in the developmentand progression of tumors. Genetic variation in the DNA sequenceof the IL-16 gene may lead to altered cytokine production and/oractivity, and this variation may modulate an individual's susceptibilityto both colorectal cancer (CRC) and gastric cancer (GC). Totest this hypothesis, we investigated the association of IL-16gene polymorphisms with serum levels of IL-16 and the risk ofCRC and GC in a Chinese population. We analyzed single-nucleotidepolymorphisms of the IL-16 gene in 596 cancer patients (376patients with CRC and 220 patients with GC), and also in 480age- and sex-matched controls using polymerase chain reaction–restrictionfragment length polymorphism and DNA sequencing methods. SerumIL-16 levels were measured by enzyme-linked immunosorbent assay.The rs11556218 T/G polymorphism of the IL-16 gene was significantlyassociated with the susceptibility to CRC and GC patients. Bothmale and female patients carrying the G allele had a significantlyhigher risk for developing CRC and GC compared with individualscarrying the T allele. Alternatively, women carrying the T allele(rs4072111 C/T) showed a decreased risk for CRC and GC comparedwith individuals carrying the C allele. In patients with CRCor GC, IL-16 serum levels were significantly higher than thosein the healthy controls, although no significant associationbetween IL-16 polymorphisms and serum levels of IL-16 was observed.Our data indicate that IL-16 polymorphisms may contribute toCRC and GC susceptibility. Abbreviations: CI, confidence interval; CRC, colorectal cancer; GC, gastric cancer; IL, interleukin; OR, odds ratio; SNP, single-nucleotide polymorphism     

Variants of Interleukin-16 Associated with Gastric Cancer Risk

Aim: We conducted a case-control matched study to investigate the role of IL-16 gene polymorphisms,rs4072111, rs1131445, rs4778889 and rs11556218, in the risk of gastric cancer in a Chinese population, alsoperforming subgroup analysis by subsites. Methods: To test the hypothesis of involvement, we analyzed the fourSNPs of IL16 in 347 cancer patients and 368 controls. Demographic data and other information were collectedusing a newly designed questionnaire. Genotyping of IL16 (rs4072111, rs1131445, rs4778889 and rs11556218)was performed in a 384-well plate format on the MassARRAY® platform. Results: In our study, we found thegastric cancer patients were more likely to be male and have a family history of cancer (P < 0.05). We foundthe rs4778889 CC and rs11556218 GG genotype was significantly associated with 1.97 and 1.84-fold increasedrisk of non-cardia gastric cancer, while we did not find significant association between the four IL-16 SNPs andcardia gastric cancer. Conclusions: In conclusion, our study indicated that IL-16 rs4778889 CC and rs11556218GG genotypes are associated with an increased risk of non-cardia gastric cancer in a Chinese population. Ourresults offer insights into the influence of IL-16 on development of gastric cancer.     

Association between a functional insertion/deletion polymorphism in IL1A gene and risk of papillary thyroid carcinoma

The aim of this study was to evaluate whether an insertion/deletion polymorphism (rs3783553) locating in the miR-122 target gene IL1A 3′ untranslated region was related to the risk of papillary thyroid carcinoma (PTC). Genomic DNA was extracted from peripheral venous blood of 273 patients with PTC and 509 controls. The IL1A rs3783553 polymorphism was genotyped by using a polymerase chain reaction assay. No significant difference of the distribution of the IL1A rs3783553 polymorphism was observed between PTC patients and controls. However, patients carrying the IL1A rs3783553 ins/ins genotype and ins allele had significantly decreased risks for developing T3 and T4 when compared with patients carrying the IL1A rs3783553 del/del genotype and del allele (ins/ins vs. del/del: OR?=?0.22, 95 % confidence interval (CI), 0.09–0.54; ins vs. del: OR?=?0.58, 95 % CI, 0.41–0.83, respectively). These results suggest that the rs3783553 polymorphism may be used as a genetic marker to predict the size/extension of PTC.     

Association between microRNA genetic variants and susceptibility to colorectal cancer in Chinese population

MicroRNAs (miRNAs) play an important role in the pathogenesis of neoplasm. Single nucleotide polymorphisms (SNPs) within miRNAs can change their phenotype and function. We attempted to analyze the relationship between two SNP loci in miRNAs and colorectal cancer (CRC) in Chinese Han population. We genotyped the polymorphism of two common miRNA SNPs, miR-146a (rs2910164 G > C) and miR-499 (rs3746444 T > C), in a case–control study of 276 CRC cases and 373 healthy controls using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). The genotypes and allele frequencies of the two SNP loci were first compared between patients and controls and then further analyzed among subgroups of patients with different clinicopathological profiles. The rs2910164 CG genotype was significantly associated with a decreased risk of CRC [CG versus GG, odds ratio (OR)?=?0.567; 95 % confidence intervals (CIs)?=?0.338–0.952; p?=?0.031]. No significant differences of miR-499 genotype and allele distribution were detected between patients and controls. Comparison between groups divided by clinicopathologic features showed that the polymorphism of miR-146a was associated with the degree of tumor differentiation (p?=?0.014), and the G allele of rs2910164 trended to a mature differentiation (OR?=?0.553; 95 % CI?=?0.315–0.971; p?=?0.038). MiR-146a (rs2910164 G > C) polymorphism is associated with CRC susceptibility and histological differentiation in Chinese Han population.     

Positive Association Between IL-16 rs11556218 T/G Polymorphism and Cancer Risk: a Meta-analysis

Background: Interleukin-16 (IL-16) is a multifunctional cytokine which plays a key role in inflammatory andautoimmune diseases as well as in cancer. Genetic polymorphisms of IL-16 have been implicated in susceptibilityto cancer. However, associations remain inconclusive. The present meta-analysis was therefore carried out toestablish a more conclusive association of IL-16 polymorphisms with cancer risk. Materials and Methods: Relevantstudies were searched through the PubMed, Embase, Web of Science, Google Scholar and Wan fang electronicdatabases updated in October 2013. Odds ratios (OR) and 95% confidence intervals (95% CI) were used toassess the association between IL-16 polymorphisms and cancer risk. Results: Eight eligible studies (rs4778889T/C: 8, rs11556218 T/G: 7, rs4072111 C/T: 6) that met our selection criteria were included. The meta-analysisindicated that rs11556218 T/G was associated with a significant increased risk of cancer (G vs. T, OR=1.321,95% CI=1.142-1.528, P ﹤0.001; TG vs. TT, OR=1.665, 95% CI=1.448-1.915, P﹤0.001; GG+TG vs. TT, OR=1.622,95% CI=1.416-1.858, P﹤0.001),as well as nasopharyngeal carcinoma and colorectal cancer. Furthermore, in thesubgroup of Chinese, significant associations were found between rs11556218 polymorphism and cancer risk.There was no statistically significant association between the other two variants (rs4778889, rs4072111) and riskof cancer. Conclusions: This meta-analysis suggests that the IL-16 rs11556218 polymorphism is associated withincreased cancer risk. Large well-designed studies involving various cancer types and different populations arenow needed.     

Association of IL-1 polymorphisms and IL-1 serum levels with susceptibility to nasopharyngeal carcinoma

Previous studies demonstrated that the polymorphism of interleukin-1 (IL-1) produce alterations of the protein expression and may contribute to oncogenetic processes. The aim of this study was to investigate the relationship between IL-1A gene polymorphisms and NPC susceptibility and the influence of on IL-1α serum levels in cases versus controls. To test whether the genetic variants of IL-1A gene modify the risk of nasopharyngeal carcinoma (NPC), we compared the -889C/T and rs3783553 polymorphisms between 248 patients with NPC and 296 healthy controls using polymerase chain reaction-restriction fragment length polymorphism. Serum IL-1α levels were measured by enzyme-linked immunosorbent assay. The rs3783553 (TTCA insertion or deletion) polymorphism of the IL-1A gene was significantly associated with the susceptibility to NPC. The variant homozygote genotype +/+ was associated with a significantly reduced risk of NPC as compared with the wild homozygote -/- genotype, and the serum IL-1α levels were significantly lower in individuals with homozygous +/+ genotypes. No association was found between the -889C/T polymorphisms and risk of NPC, and no statistically significant differences were found between rs3783553 polymorphism and clinical pathology indices. The IL-1A rs3783553 polymorphism might contribute to a risk of developing NPC by affecting the serum IL-1α secretion in the Chinese population.     

Correlation between genetic polymorphisms within IL-1B and TLR4 genes and cancer risk in a Russian population: a case-control study

In the last decade, a growing interest has been devoted to the evaluation of the impact of single nucleotide polymorphisms (SNP) on cancer risk. According to the results of multiple studies, among the genes that have a considerable influence on cancer risk are those encoding pattern recognition receptors, cytokines, and antioxidant defense enzymes. Nonetheless, the effect of numerous SNPs within these genes on cancer risk has been scarcely investigated. A case-control study of 401 cases and 300 sex- and age-matched controls was performed in order to explore the role of IL1B_1473G/C (rs1143623), SOD1_7958A/G (rs4998557), TLR4_1196C/T (rs4986791), IL10_1082A/G (rs1800896), IL17A_197G/A (rs2275913), and TLR4_896A/G (rs4986790) polymorphisms in the susceptibility to colorectal cancer (n?=?244), gastric carcinoma (n?=?72), and ovarian cancer (n?=?85). The analysis revealed a significant relationship between the presence of heterozygous genotypes for IL1B_1473G/C and TLR4_896A/G polymorphisms and higher risk of rectal cancer (codominant model, OR?=?1.67; 95 % CI, 1.06–2.63; p?=?0.048 and OR?=?2.25; 95 % CI, 1.26–4.02; p?=?0.014, respectively). In addition, the variant G/G genotype of the IL10_1082A/G SNP was associated with a 2.5-fold increase in ovarian cancer risk with a borderline significance (codominant model, OR?=?2.45; 95 % CI, 1.14–5.25; p?=?0.069). Similarly, the carriers of the C/T genotype for the TLR4_1196C/T polymorphism were more susceptible to rectal cancer with a borderline significance (codominant model, OR?=?1.42; 95 % CI, 0.80–2.51 p?=?0.06). No statistically significant associations were found when stratifying the sample by subgroups of age, sex, and clinicopathological characteristics. Finally, we observed six combinations of haplotypes for the examined SNPs, each of which either profoundly increased or decreased cancer risk. The results from our study provided evidence that IL1B_1473G/C and TLR4_896A/G SNPs are implicated in rectal cancer development in a Russian population. Further research should be addressed to clarify the role of the abovementioned polymorphisms in cancer etiology.     

Association of variants in the interleukin‐27 and interleukin‐12 gene with nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is multifactorial, and the genetic background may be a crucial etiologic factor. Interleukin‐12 (IL‐12) is a multifunctional cytokine that induces interferon (IFN)‐gamma secretion and plays an important role in antitumor immunity. Interleukin‐27 (IL‐27) is a novel IL‐12 family member, the present studies demonstrate that IL‐27 mediates potent antitumor activity. Variations in the DNA sequence in the IL‐12 and IL‐27 gene may lead to altered cytokines production and/or activity, and so this can modulate an individual's susceptibility to NPC. To test this hypothesis, we investigated the relationship of IL‐12 and IL‐27 gene polymorphisms and NPC in a Chinese population. We analyzed single nucleotide polymorphisms (SNPs) of IL‐12 gene 16974 A/C and IL‐27 gene ?964 A/G, 2905 T/G, 4730 T/C in 302 patients with NPC and 310 age‐ and sex‐matched controls, using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and DNA sequencing methods. There were significant differences in the genotype and allele distribution of 16974 A/C polymorphism of the IL‐12 gene among cases and controls. The 16974 CC and AC genotypes were associated with a significantly increased risk of NPC as compared with the 16974 AA genotypes (OR = 2.225, 95% CI 1.395–3.549, P = 0.001 and OR = 1.834, 95% CI 1.239–2.716, P = 0.002, respectively). The 16974 C allele was associated with a significantly increased risk of NPC as compared with the 16974 A allele (OR = 1.334, 95% CI 1.065–1.670, P = 0.012). However, genotype and allele frequencies of the IL‐27 gene ?964 A/G, 2905 T/G, 4730 T/C polymorphisms in NPC patients were not significantly different than that in healthy controls (P > 0.05). Our data suggest that IL‐12 gene may play a role in the development of NPC. © 2009 Wiley‐Liss, Inc.     

Significant association between interleukin-17A polymorphism and colorectal cancer

Interleukin (IL) 17A is an inflammatory cytokine expressed by Th 17 cells and plays a role in tissue inflammation by inducing release of proinflammatory and neutrophil-mobilizing cytokines. We have investigated the association between colorectal cancer and polymorphisms of IL17A (rs2275913. G197A). The study was performed in 241 subjects (102 with colorectal cancer and 139 healthy controls). Genotypes were determined by fluorescent-based restriction fragment length polymorphism method. The association between the molecular features at the gene in relation to tumor and patient clinical characteristics was analyzed. There was a significant difference between the genotype frequencies of IL17A G197A of control subjects (GG 68.34 % and GA + AA 31.65 %) and patients with colorectal cancer (GG 47.05 % and GA + AA 52.94 %) (p?=?0.001with odds ratio (OR) 2.45 (1.43–4.11)). IL17A G197A polymorphism is particularly associated with colon cancer. Indeed, the IL17A GG genotype could be considered as a protective factor against colon cancer (p?=?0.00001) with OR 3.77 (2.04–6.99). We have noted a significant association of IL17A G197A polymorphism not only with tumor localization (p?=?0.003) but also with tumor differentiation (p?=?0.0005) in CRC patients. We have also showed a significant association of G197A variant with an increased risk of advanced stage (p?=?0.005). Our result suggests that the A allele of IL17A gene is involved in susceptibility to colorectal cancer and is associated with clinical features as tumor location, tumor differentiation, and TNM stage. IL17A polymorphism may serve as biomarker of disease location and progression.     

Interactions of miR-34b/c and TP-53 polymorphisms on the risk of nasopharyngeal carcinoma

Growing evidence indicates that tumor suppressor gene TP-53 and non-coding RNA miR-34b/c independently and/or jointly play crucial roles in carcinogenesis. We hypothesized that the polymorphisms of rs4938723 in the promoter region of pri-miR-34b/c and TP-53 Arg72-Pro may be related to the risk of nasopharyngeal carcinoma (NPC). We performed a case–control study between 217 patients with NPC and 360 healthy controls in a Chinese population using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. A significantly increased risk of NPC was observed in the miR-34b/c rs4938723 CT/CC genotypes compared with the TT genotype (adjusted OR?=?1.44, 95 % CI 1.02–2.03, p?=?0.04), and also the C allele (adjusted OR?=?1.33, 95 % CI 1.04–1.70, p?=?0.03). The gene–gene interaction of miR-34b/c rs4938723 and TP-53 Arg72-Pro showed that the combined genotypes of rs4938723CT/CC and TP-53CG/CC increased the risk of NPC (rs4938723CT/CC?+?TP-53CG/CC vs. rs4938723 TT?+?TP-53 CG/CC: OR?=?1.58, 95 % CI 1.04–2.42, p?=?0.03). These findings suggest that miR-34b/c rs4938723 and TP-53 Arg72Pro polymorphisms may singly or collaboratively contribute to the risk of NPC.     

The effect of lysyl oxidase polymorphism on susceptibility and prognosis of nonsmall cell lung cancer

Lysyl oxidase (LOX) is a copper-dependent amine oxidase that plays important roles in development and homeostasis of the lungs. The aim of this study was to investigate whether polymorphisms in the LOX gene were associated with susceptibility to nonsmall cell lung cancer (NSCLC). We sequenced the promoter region of LOX gene and tested the previously reported polymorphism 473?G/A in the Han Chinese population. A novel polymorphism, ?22?G/C, was identified in the promoter region of LOX. However, it did not show any correlation with NSCLC. Frequencies of the 473AA genotype and 473A allele were significantly higher in the NSCLC cases than in control group (p?=?0.004 and p?=?0.006, respectively). Further, our results showed that survival time of NSCLC patients with 473AA genotype was significantly shorter compared to the cases carrying 473?G allele (20.0?months vs. 28.0?months, p?=?0.011). These data indicate that LOX 473?G/A polymorphism is associated with increased risk of NSCLC and can be a prognostic predictor for this disease.     

A let-7 binding site polymorphism rs712 in the KRAS 3′ UTR is associated with an increased risk of gastric cancer

Recently, single nucleotide polymorphisms in let-7 miRNA binding site in 3′ untranslated region (UTR) of KRAS mRNA have been found to be associated with the cancer risk. In this study, we genotyped the frequency of KRAS rs712 to test its effect on gastric cancer (GC) risk in a hospital-based case–control study in a Chinese population, with 181 histologically confirmed GC patients and 674 cancer-free controls, using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. The TT genotype of rs712 was associated with an increased risk of GC when taking GG genotype as a reference (adjusted odds ratio (OR)?=?3.05, 95 % confidence interval (CI), 1.53–6.08). Similarly, the T allele of rs712 was associated with a statistically significant increase in susceptibility compared with G allele (adjusted OR?=?1.44, 95 % CI, 1.10–1.90). Our data demonstrated that the T allele of the let-7 binding site polymorphism rs712 in KRAS 3′ UTR was associated with a significantly increased risk of GC, suggesting that the KRAS rs712 polymorphism may be a genetic marker for the development of GC.     

Analysis of the association of interleukin-17 gene polymorphisms with gastric cancer risk and interaction with Helicobacter pylori infection in a Chinese population

We aimed to explore the association between interleukin-17 (IL-17) polymorphisms, Helicobacter pylori infection, and subsites in gastric cancer risk in a Chinese population. We genotyped three promoter polymorphisms (rs2275913G>A, rs3748067C>T, and rs763780T>C) of IL-17 in a case–control study of 260 gastric cancer patients and 512 healthy controls. An unconditional multiple logistical regression model was used to calculate the effects of IL-17 gene polymorphisms on gastric cancer risk. The rs2275913 AA (adjusted OR?=?1.69, 95 % CI?=?1.15–2.49) and rs3748067 TT (adjusted OR?=?1.73, 95 % CI?=?1.03–2.94) genotypes were associated with an increased risk of gastric cancer. We observed a significant interaction among rs2275913G>A, rs3748067C>T, and H. pylori infection on the risk of gastric cancer (p for interaction of 0.036 and 0.048, respectively). H. pylori infection subjects carrying the rs2275913 AA (adjusted OR?=?2.48, 95 % CI?=?1.49–4.12) and rs3748067 TT (adjusted OR?=?2.54, 95 % CI?=?1.34–5.12) genotypes had a greatly increased risk of gastric cancer compared to negative H. pylori participants. Similarly, subjects carrying the rs2275913 AA (adjusted OR?=?2.09, 95 % CI?=?1.25–3.45) and rs3748067 TT (adjusted OR?=?2.29, 95 % CI?=?1.20–4.20) genotypes had a moderately increased risk of noncardia gastric cancer. A significant interaction was observed between the rs2275913G>A and rs3748067C>T genotype and subsites of gastric cancer (p for interaction of 0.044 and 0.008, respectively). The rs2275913G>A and rs763780T>C polymorphisms increase gastric cancer risk, and interact with H. pylori infection and subsites. These findings could be helpful in identifying individuals at increased risk for developing gastric cancer.     

Cytokine and chemokine modification by Toll-like receptor polymorphisms is associated with nasopharyngeal carcinoma

Toll-like receptors (TLR) play a pivotal role in sensing a wide range of pathogens, including bacteria, fungi and viruses. A dysregulation of TLR signaling may increase the risk of developing chronic inflammatory diseases and cancers. The aim of this study was to investigate the association of TLR2 R753Q, TLR4 D299G, and T399I polymorphisms with nasopharyngeal carcinoma (NPC) and to explore the effects of these polymorphisms on cytokine and chemokine expression in NPC biopsies. The genotypes of the three loci among 236 patients with NPC and 287 healthy controls were determined by PCR-RFLP. Cytokines and chemokines mRNA and protein in NPC biopsies were measured by real-time quantitative PCR and ELISA, respectively. Results showed that the combined CT/TT genotype of T399I was associated with increased NPC risk, with an odds ratio of 1.853 (95% confidence interval: 1.184-2.961). Also, individuals with the T allele of T399I showed a 1.842-fold increase in NPC risk compared to those with the T399I C allele (95% confidence interval: 1.213-3.015). Messenger RNA levels of interleukin (IL)-1α, tumor necrosis factor-α and IL-10 were significantly elevated in patients with T399I combined CT/TT genotype; IL-1α and IL-10 protein concentration significantly increased in NPC patients with T399I combined CT/TT genotype compared to those with the T399I CC genotype. Our data suggest that TLR4 T399I modify cytokines and chemokines patterns and play a role in the development of NPC.     

Relationships between genetic polymorphisms in inflammation-related factor gene and the pathogenesis of nasopharyngeal cancer

Our study aims to discuss the association between inflammation-related factors such as single nucleotide polymorphisms (SNPs) with susceptibility and recurrence in nasopharyngeal carcinoma. We used Taqman real-time polymerase chain reaction (PCR) to characterize the genetic variation of five SNPs in 194 nasopharyngeal carcinoma patients and 231 healthy subjects. All statistical analysis is performed with statistical product and service solutions v13.0; odds ratio (OR) value and 95 % confidence interval (CI) were calculated. There is no relationship between TGFβ1 –869 T/C, IL-6 –634C/G, TGFβ1 –509C/T, IL1 –511C/T and nasopharyngeal carcinoma susceptibility. Both single factor and multiple factors analysis showed that IL1a –889 T/T genotype is significantly associated with nasopharyngeal carcinoma in decreasing the risk of nasopharyngeal carcinoma. A highly significant association was found between IL1a –889 T/T genotype and protective genotype as defined by various pathological types. This is more obvious in the protective genotype of the non-keratin-type squamous carcinoma undifferentiated type. We also discovered that genotype G/G and C/G?+?G/G of IL6 –634 gene are associated with reduced recurrence of nasopharyngeal carcinoma. IL1a –889 gene polymorphism and susceptibility is related to nasopharyngeal carcinoma and can potentially decrease the risk of nasopharyngeal carcinoma in the Han Chinese population in north China. IL1-889 TT genotype is protective genotype for nasopharyngeal carcinoma. We have provided evidence that the GG genotype of the IL6 –634 gene is associated with recurrent risk of nasopharyngeal carcinoma. The G allele is the protective gene of nasopharyngeal carcinoma recurrence.     

Common genetic variants at 1q22 and 10q23 and gastric cancer susceptibility in a Korean population

Genetic variants at 1q22 and 10q23 were identified as genetic markers of both gastric cancer and esophageal squamous cell carcinoma susceptibility by two genome-wide association studies. The aim of this study was to determine whether rs4072037A?>?G in MUC1 at 1q22 and rs2274223A?>?G in PLCE1 at 10q23 are associated with a risk of gastric cancer in a Korean population. We conducted a large-scale case–control study of 3,245 patients with gastric cancer and 1,700 controls. The allele frequencies of rs4072037G and rs2274223G were 11.2 and 25.5 % among patients with gastric cancer, compared with 12.8 and 26.4 %, respectively, among controls. We found that the rs4072037 AG genotype was significantly associated with a reduced risk of gastric cancer [odds ratios (OR)?=?0.78; 95 % confidence interval (CI)?=?0.67–0.91 for AG vs AA]. Compared with the rs2274223 AA genotype, we found a significant association between the rs2274223 AG genotype and a weakly reduced risk of gastric cancer (OR?=?0.87; 95 % CI?=?0.76–0.99 for AG vs AA). Our data suggest that genetic variants at 1q22 and 10q23 play a role in gastric carcinogenesis.     

Prognostic value of PDCD6 polymorphisms and the susceptibility to bladder cancer

Programmed cell death 6 (PDCD6) has recently been found dysregulated in tumors of various origin. The aim of this study is to explore the association between PDCD6 genetic polymorphisms and susceptibility to bladder cancer and survival of patients with bladder cancer. Two tag SNPs of PDCD6, rs3756712 and rs4957014, were genotyped in 332 patients with bladder cancer and 509 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and correlated with patients’ survival. The frequencies of G allele and GG genotype of rs3756712 in patients were significantly lower than that of controls (P?=?0.001, odds ratio [OR]?=?0.68 for G allele; P?=?0.024, OR?=?0.53 for GG genotype in the recessive genetic model, respectively). The GT genotype of rs4957014 was associated with decreased susceptibility to bladder cancer in the overdominant genetic model (P?=?0.023, OR?=?0.72). Kaplan–Meier curves revealed a significant higher risk for death in superficial bladder cancer patients harboring GG homozygous of rs3756712 (P?P?=?0.04). Multiple Cox regression analysis identified rs3756712 GG genotype as an independent prognostic factor for death in superficial bladder cancer patients (hazard ratio [HR]?=?5.11, P?=?0.01), and rs4957014 GT genotype as an independent prognostic factor for recurrence in invasive bladder cancer patients (HR?=?1.93, P?=?0.03). PDCD6 may represent a biomarker candidate gene that could help to identify a group of patients at high risk for recurrence and death.     

Genetic polymorphisms of NFκB1-94ins/delATTG and NFκBIA-881A/G genes in Egyptian patients with colorectal cancer

To assess the association of genetic polymorphisms of NFκB1 and NFκBIA genes with the susceptibility to colorectal cancer (CRC). Subjects included 100 Egyptian patients with CRC (60 males and 40 females) in addition to 85 healthy controls (47 males and 38 females) from the same locality. For all participants, genetic polymorphisms of NFκB1-94ins/delATTG (rs28362491) and NFκBIA-881A/G (rs3138053) were detected by using restriction fragment length polymorphism polymerase chain reaction (RFLP–PCR). CRC patients showed a significantly higher frequency of the NFκB1-94ins/ins genotype than controls (30 vs. 4.7%) that was significant in the recessive (OR?17.69, 95% CI? ?5.41–57.82, p?<?0.0001) and codominant models (OR? ?18.28, 95% CI? ?4.87–68.6, p?<?0.0001). The NFκB1-94ins allele frequency was significantly higher among patients than controls (58 vs. 39%, OR? 2.18, 95% CI? 1.4–3.3, p?=?0.0004). We also noticed that the genotype G/G of NFκBIA-881 polymorphism was present in patients (4%) while it was absent (0%) in controls with increased frequency of the NFκBIA-881G allele in patients compared to controls (23 vs. 14%, p?=?0.041). These polymorphisms were more associated with smoking and advanced tumor staging. This study indicates that the NFκB1-94ins/ins genotype was associated with the risk of developing colorectal cancer in Egyptian subjects. Also, CRC cases showed an increase in the frequency of NFκBIA-881G allele but not reaching statistical significance for multiple comparisons.