A case-control study including 494 ESCC patients and 494 controls was carried out to investigate the genetic susceptibility of 4 microRNA-binding site SNPs (rs712 in the binding site of KRAS to let-7, rs8904 in the binding site of NFBIA to mir-507, rs3738894 in the binding site of protein kinase C epsilon to mir-218, rs701848 in the binding site of phosphatase and tensin to mir-1304) as well as the interactions of gene-environment in the development of ESCC.
Since interleukin-1 receptor-associated kinase (IRAK-1)/nuclear factor-kappa B (NF-kappa B) pathway plays an essential role in the pathogenesis of autoimmune diseases, the aim of the present study was to explore the role of polymorphisms in three genes, named IRAK1 (rs3027898), NFKBIA (rs696) and NFKB1 (-94ATTG insertion/deletion variant, - rs28362491), in PV susceptibility.
Unconditional logistic regression revealed that carriers of the TT genotype at rs2233406 had a greater risk (OR = 5.57, 95% CI = 2.14-14.52) of chronic HBV infection progression.
In conclusion, <i>NFKB1</i> rs28362491, <i>NFKBIA</i> rs2233406 and <i>NFKBIA</i> rs696 polymorphisms may serve as biomarkers for predicting risk of AKI in children.
Two significant SNPs, rs11096957 (OR = 1.26, P = 1.35 × 10<sup>-5</sup>) and rs2273650 (OR = 1.2, P = 1.57 × 10<sup>-3</sup>), were significantly associated with HOA risk.
In conclusion, <i>NFKB1</i> rs28362491, <i>NFKBIA</i> rs2233406 and <i>NFKBIA</i> rs696 polymorphisms may serve as biomarkers for predicting risk of AKI in children.
Interestingly, multifactor dimension reduction analysis suggested an increased risks of nearly 6-folds for ESRD and 23-folds for ARE cases under the six factors model which consists of tag-SNPs of FOXP3 (rs2232365, rs3761548, rs5902434 and rs2294021) and NF-kB1 (rs28362491 and rs696).
Interestingly, multifactor dimension reduction analysis suggested an increased risks of nearly 6-folds for ESRD and 23-folds for ARE cases under the six factors model which consists of tag-SNPs of FOXP3 (rs2232365, rs3761548, rs5902434 and rs2294021) and NF-kB1 (rs28362491 and rs696).
In Caucasian patients, we identified associations between two SNPs and the incidence of AKI (stage 1 and above): rs1050851 and rs2233417; both are found within the gene for nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (NFKBIA).
Four putatively functional SNPs (NFκB1: rs28362491del>ins ATTG; NFκB2: rs12769316G>A; IκBα: rs2233406C>T and rs696G>A) were analyzed to evaluate their associations with NPC risk in total 1590 NPC cases and 1979 cancer-free controls.
In Caucasian patients, we identified associations between two SNPs and the incidence of AKI (stage 1 and above): rs1050851 and rs2233417; both are found within the gene for nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (NFKBIA).
When stratification analysis was performed by cancer type, an increased association of rs3138053 was recognized in hepatocarcinoma (C vs. T: OR=42.180, 95%CI=27.970-63.612, Pheterogeneity=0.007), while a decreased association of rs696 was identified in Hodgkin lymphoma (C vs. T: OR=0.792, 95%CI=0.656-0.956, Pheterogeneity=0.116; CC vs. TT: OR=0.658, 95%CI=0.448-0.965, Pheterogeneity=0.076; CC vs. CT+TT: OR=0.734, 95%CI=0.562-0.958, Pheterogeneity=0.347).
When stratification analysis was performed by cancer type, an increased association of rs3138053 was recognized in hepatocarcinoma (C vs. T: OR=42.180, 95%CI=27.970-63.612, Pheterogeneity=0.007), while a decreased association of rs696 was identified in Hodgkin lymphoma (C vs. T: OR=0.792, 95%CI=0.656-0.956, Pheterogeneity=0.116; CC vs. TT: OR=0.658, 95%CI=0.448-0.965, Pheterogeneity=0.076; CC vs. CT+TT: OR=0.734, 95%CI=0.562-0.958, Pheterogeneity=0.347).
Combined data demonstrated that rs3138053 polymorphism of NFKBIA was associated with cancer susceptibility in an allelic model (C vs. T: OR=10.754, 95%CI=4.175-27.697, Pheterogeneity=0.000), while the polymorphism of rs696 appeared to play a protective role in tumorigenesis (CC+CT vs. TT: OR=0.879, 95%CI=0.787-0.982, Pheterogeneity=0.107).
Combined data demonstrated that rs3138053 polymorphism of NFKBIA was associated with cancer susceptibility in an allelic model (C vs. T: OR=10.754, 95%CI=4.175-27.697, Pheterogeneity=0.000), while the polymorphism of rs696 appeared to play a protective role in tumorigenesis (CC+CT vs. TT: OR=0.879, 95%CI=0.787-0.982, Pheterogeneity=0.107).
When stratification analysis was performed by cancer type, an increased association of rs3138053 was recognized in hepatocarcinoma (C vs. T: OR=42.180, 95%CI=27.970-63.612, Pheterogeneity=0.007), while a decreased association of rs696 was identified in Hodgkin lymphoma (C vs. T: OR=0.792, 95%CI=0.656-0.956, Pheterogeneity=0.116; CC vs. TT: OR=0.658, 95%CI=0.448-0.965, Pheterogeneity=0.076; CC vs. CT+TT: OR=0.734, 95%CI=0.562-0.958, Pheterogeneity=0.347).
When stratification analysis was performed by cancer type, an increased association of rs3138053 was recognized in hepatocarcinoma (C vs. T: OR=42.180, 95%CI=27.970-63.612, Pheterogeneity=0.007), while a decreased association of rs696 was identified in Hodgkin lymphoma (C vs. T: OR=0.792, 95%CI=0.656-0.956, Pheterogeneity=0.116; CC vs. TT: OR=0.658, 95%CI=0.448-0.965, Pheterogeneity=0.076; CC vs. CT+TT: OR=0.734, 95%CI=0.562-0.958, Pheterogeneity=0.347).
Our data demonstrated that the rs3138053 polymorphism of NFKBIA gene is a candidate for susceptibility to overall cancers, while rs696 plays a protective role.
When stratification analysis was performed by cancer type, an increased association of rs3138053 was recognized in hepatocarcinoma (C vs. T: OR=42.180, 95%CI=27.970-63.612, Pheterogeneity=0.007), while a decreased association of rs696 was identified in Hodgkin lymphoma (C vs. T: OR=0.792, 95%CI=0.656-0.956, Pheterogeneity=0.116; CC vs. TT: OR=0.658, 95%CI=0.448-0.965, Pheterogeneity=0.076; CC vs. CT+TT: OR=0.734, 95%CI=0.562-0.958, Pheterogeneity=0.347).
Our findings prove that both single and combined genotype analysis of rs28362491 and rs696 polymorph</span>isms indicate that the wild genotypes of both two SNPs (ins/ins and AA genotypes) and ins/ins/AA combined genotype are strongly associated with enhanced risk of BD in a Turkish population.
When stratification analysis was performed by cancer type, an increased association of rs3138053 was recognized in hepatocarcinoma (C vs. T: OR=42.180, 95%CI=27.970-63.612, Pheterogeneity=0.007), while a decreased association of rs696 was identified in Hodgkin lymphoma (C vs. T: OR=0.792, 95%CI=0.656-0.956, Pheterogeneity=0.116; CC vs. TT: OR=0.658, 95%CI=0.448-0.965, Pheterogeneity=0.076; CC vs. CT+TT: OR=0.734, 95%CI=0.562-0.958, Pheterogeneity=0.347).