IκBα polymorphism at promoter region (rs2233408) influences the susceptibility of gastric cancer in Chinese

<p>Abstract</p> <p>Background</p> <p>Nuclear factor of kappa B inhibitor alpha (IκBα) protein is implicated in regulating a variety of cellular process from inflammation to tumorigenesis. The objective of this study was to investigate the susceptibility of rs2233408 T/C genotype in the promoter region of <it>IκBα </it>to gastric cancer and the association of this polymorphism with clinicopathologic variables in gastric cancer patients.</p> <p>Methods</p> <p>A population-based case-control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 564 gastric cancer patients and 566 healthy controls were enrolled in this study. rs2233408 genotypes in <it>IκBα </it>were analyzed by TaqMan SNP genotyping assay.</p> <p>Results</p> <p>Both rs2233408 T homozygote (TT) and T heterozygotes (TC and TT) had significantly reduced gastric cancer risk (TT: OR = 0.250, 95% CI = 0.069-0.909, <it>P </it>= 0.035; TC and TT: OR = 0.721, 95% CI = 0.530-0.981, <it>P </it>= 0.037), compared with rs2233408 C homozygote (CC). rs2233408 T heterozygotes were significantly associated with reduced risk of intestinal-type gastric cancer with ORs of 0.648 (95% CI = 0.459-0.916, <it>P </it>= 0.014), but not with the diffuse or mix type of gastric cancer. The association between rs2233408 T heterozygotes and gastric cancer appeared more apparent in the older patients (age>40) (OR = 0.674, 95% CI = 0.484-0.939, <it>P </it>= 0.02). rs2233408 T heterozygotes was associated with non-cardiac gastric cancer (OR = 0.594, 95% CI = 0.411-0.859, <it>P </it>= 0.006), but not with cardiac gastric cancer. However, rs2233408 polymorphism was not associated with the prognosis of gastric cancer patients.</p> <p>Conclusions</p> <p><it>IκBα </it>rs2233408 T heterozygotes were associated with reduced risk of gastric cancer, especially for the development of certain subtypes of gastric cancer in Chinese population.</p

Tumour necrosis factor gene polymorphism: a predictive factor for the development of post-transplant lymphoproliferative disease

Epstein–Barr virus-positive post-transplant lymphoproliferative disease (PTLD) is a potentially lethal complication of iatrogenic immunosupression after transplantation. Predicting the development of PTLD allowing early and effective intervention is therefore of importance. Polymorphisms within cytokine genes are implicated in susceptibility to, and progression of, disease however the published data are often conflicting. We undertook investigation of polymorphic alleles within cytokine genes in PTLD and non-PTLD transplant cohorts to determine risk factors for disease. &lt;br/&gt; Methods: SSP-PCR was used to analyse single nucleotide polymorphism within tumour necrosis factor (TNF)-α, interleukin- 1, -6, -10 and lymphotoxin-α genes. The TNF-α levels were measured by standard enzyme-linked immuno-absorbant assay. &lt;br/&gt; Results: We show an association between variant alleles within the TNF-α promoter (−1031C (&lt;i&gt;P&lt;/i&gt;=0.005)); −863A (&lt;i&gt;P&lt;/i&gt;=0.0001) and TNF receptor I promoter regions (−201T (&lt;i&gt;P&lt;/i&gt;=0.02)); −1135C (&lt;i&gt;P&lt;/i&gt;=0.03) with the development of PTLD. We also show an association with TNF-α promoter haplotypes with haplotype-3 significantly increased (&lt;i&gt;P&lt;/i&gt;=0.0001) and haplotype-1 decreased (P=0.02) in PTLD patients compared to transplant controls. Furthermore, we show a significant increase (&lt;i&gt;P&lt;/i&gt;=0.02) in the level of TNF-α in PTLD patient plasma (range 0–97.97 pg ml&lt;sup&gt;−1&lt;/sup&gt;) compared to transplant controls (0–8.147 pg ml&lt;sup&gt;−1&lt;/sup&gt;), with the highest levels found in individuals carrying the variant alleles. &lt;br/&gt; Conclusion: We suggest that genetic variation within TNF-α loci and the level of plasma cytokine could be used as a predictive risk factor for the development of PTLD

Polymorphisms in NF-κB Inhibitors and Risk of Epithelial Ovarian Cancer

<p>Abstract</p> <p>Background</p> <p>The nuclear factor-κB (NF-κB) family is a set of transcription factors with key roles in the induction of the inflammatory response and may be the link between inflammation and cancer development. This pathway has been shown to influence ovarian epithelial tissue repair. Inhibitors of κB (IκB) prevent NF-κB activation by sequestering NF-κB proteins in the cytoplasm until IκB proteins are phosphorylated and degraded.</p> <p>Methods</p> <p>We used a case-control study to evaluate the association between single nucleotide polymorphisms (SNPs) in <it>NFKBIA </it>and <it>NFKBIB </it>(the genes encoding IκBα and IκBβ, respectively) and risk of epithelial ovarian cancer. We queried 19 tagSNPs and putative-functional SNPs among 930 epithelial ovarian cancer cases and 1,037 controls from two studies.</p> <p>Results</p> <p>The minor allele for one synonymous SNP in <it>NFKBIA</it>, rs1957106, was associated with decreased risk (p = 0.03).</p> <p>Conclusion</p> <p>Considering the number of single-SNP tests performed and null gene-level results, we conclude that <it>NFKBIA </it>and <it>NFKBIB </it>are not likely to harbor ovarian cancer risk alleles. Due to its biological significance in ovarian cancer, additional genes encoding NF-κB subunits, activating and inhibiting molecules, and signaling molecules warrant interrogation.</p

Effects of NFKB1 and NFKBIA Gene Polymorphisms on Susceptibility to Environmental Factors and the Clinicopathologic Development of Oral Cancer

encoding IkappaBalpha (IκBα) with both the susceptibility to develop OSCC and the clinicopathological characteristics of the tumors.<.05), compared with those patients CC homozygotes. 519 might be a predictive factor for the distal metastasis of OSCC in Taiwanese

Haplotypic structure across the IκBα gene (<i>NFKB1A</i>) and association with multiple myeloma

Haplotypic structure across the I kappa B alpha gene (NFKB1A) and association with multiple myeloma Polymorphisms in NFKBIA may be important in pre-disposition to and outcome after treatment, of multiple myeloma (MM). The NFKBIA gene product, I kappa B alpha, binds to NF-kappa B preventing its activation and is important in mediating resistance to apoptosis in B-cell lymphoproliferative diseases. This study investigates eight polymorphisms across the NFKBIA gene in large patient and control populations. Significant differences in the frequency of particular polymorphisms were noted between patients and controls. A risk haplotype [GCCTATCA] for MM was also identified (P= 0.006). Analysis of the genetics of NFKBIA may lead to associations with disease progression and survival and thus more personalized therapy. (c) 2006 Elsevier Ireland Ltd. All rights reserved