Functional promoter -94 ins/del ATTG polymorphism in NFKB1 gene is associated with bladder cancer risk in a Chinese population.
Functional promoter -94 ins/del ATTG polymorphism in NFKB1 gene is associated with bladder cancer risk in a Chinese population.
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NFKB1基因中的功能启动子-94 INS/DEL ATTG多态性与中国人群中的膀胱癌风险有关。
DOI：
10.1371/journal.pone.0071604
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gu M
中科院分区：
文献类型：
--
作者：
Li P;Gu J;Yang X;Cai H;Tao J;Yang X;Lu Q;Wang Z;Yin C;Gu M
据报道，NFKB 1基因启动子中的功能性-94插入/缺失多态性（rs 28362491）影响NFKB 1表达并赋予对不同类型癌症的易感性。本研究旨在确定该多态性是否与膀胱癌的风险相关。采用TaqMan方法检测609例病例和640例对照的基因型。采用Logistic回归分析该多态性与膀胱癌风险之间的关系，并采用实时定量聚合酶链反应测定NFKB 1 mRNA表达。与ins/ins/ins/del基因型相比，del/del基因型与膀胱癌发病风险显著增加相关[校正比值比（OR）= 1.92，95%可信区间（CI）= 1.42-2.59]。 65岁以上受试者（OR = 2.37，95%CI = 1.52-3.70）、男性受试者（OR = 1.97，95%CI = 1.40-2.79）和自报癌症家族史受试者（OR = 3.59，95%CI = 1.19-10.9）的风险增加更为突出。 此外，该基因多态性与非肌层浸润性膀胱癌（OR = 2.07，95%CI = 1.51-2.85）、1级膀胱癌（OR = 2.40，95%CI = 1.68-3.43）、单肿瘤膀胱癌（OR = 2.04，95%CI = 1.48-2.82）和较小肿瘤膀胱癌（OR = 2.10，95%CI = 1.51-2.92）的发生风险较高相关。 NFKB 1基因插入纯合型膀胱癌组织中NFKB 1 mRNA的表达高于缺失型。结论：NFKB 1基因启动子区-94 ins/del ATTG多态性可能与中国人群膀胱癌的发生有关。
A functional -94 insertion/deletion polymorphism (rs28362491) in the promoter of the NFKB1 gene was reported to influence NFKB1 expression and confer susceptibility to different types of cancer. This study aims to determine whether the polymorphism is associated with risk of bladder cancer. TaqMan assay was used to determine genotype among 609 cases and 640 controls in a Chinese population. Logistic regression was used to assess the association between the polymorphism and bladder cancer risk, and quantitative real-time polymerase chain reaction was used to determine NFKB1 mRNA expression. Compared with the ins/ins/ins/del genotypes, the del/del genotype was associated with a significantly increased risk of bladder cancer [adjusted odd ratio (OR) = 1.92, 95% confidence interval (CI) = 1.42–2.59]. The increased risk was more prominent among subjects over 65 years old (OR = 2.37, 95% CI = 1.52–3.70), male subjects (OR = 1.97, 95% CI = 1.40–2.79) and subjects with self-reported family history of cancer (OR = 3.59, 95% CI = 1.19–10.9). Furthermore, the polymorphism was associated with a higher risk of developing non-muscle invasive bladder cancer (OR = 2.07, 95% CI = 1.51–2.85), grade 1 bladder cancer (OR = 2.40, 95% CI = 1.68–3.43), single tumor bladder cancer (OR = 2.04, 95% CI = 1.48–2.82) and smaller tumor size bladder cancer (OR = 2.10, 95% CI = 1.51–2.92). The expression of NFKB1 mRNA in bladder cancer tissues with homozygous insertion genotype was higher than that with deletion allele. In conclusion, the -94 ins/del ATTG polymorphism in NFKB1 promoter may contribute to the etiology of bladder cancer in the Chinese population.
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