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干扰素-γ+874A 多态性与印度北部人群宫颈癌发病风险的关联。

Association of interferon-gamma +874A polymorphism with the risk of developing cervical cancer in north-Indian population.

机构信息

Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, India.

出版信息

BJOG. 2009 Nov;116(12):1671-7. doi: 10.1111/j.1471-0528.2009.02307.x. Epub 2009 Aug 14.

DOI:10.1111/j.1471-0528.2009.02307.x
PMID:19681846
Abstract

OBJECTIVE

Interferon gamma (IFN-gamma) is a pro-inflammatory cytokine playing a pivotal role in both innate and adaptive immune responses. A single nucleotide polymorphism located in the first intron of the human IFN-gamma gene can influence the secretion of cytokine. Therefore, we aimed to investigate the association of IFN-gamma T/A gene polymorphism with the risk of cervical cancer.

DESIGN

Case-control study.

SETTING

Uttar Pradesh State in India.

SAMPLE

Two hundred cases with histologically proven cancer of the cervix and healthy controls (n = 230), age and ethnicity matched were recruited in this study.

METHODS

Genotyping was performed for bi-allelic +874 (T/A) polymorphism of IFN-gamma by amplification refractory mutation system method.

MAIN OUTCOME MEASURES

Low producer IFN-gamma +874 AA genotype was associated with high risk for cervical cancer, which further modulated the increased risk in tobacco users.

RESULTS

IFN-gamma AA genotype which is low producer of IFN-gamma was associated with increased risk of cervical cancer (OR = 2.43, P = 0.003). Allele A was at 1.54-fold increased risk of cervical cancer (OR=1.54, P = 0.002). The AA genotype showed statistically significant risk with high stage (III + IV) of cervical cancer (OR = 4.99, P = 0.001). In tobacco users, AA genotype showed significantly increased susceptibility to cervical cancer (OR = 5.08, P = 0.010).

CONCLUSION

Variation in IFN-gamma +874 AA genotype because of ethnicity in north-Indian population may represent an important susceptibility biomarker for cervical cancer risk as well as other diseases and should be explored further.

摘要

目的

干扰素γ(IFN-γ)是一种促炎细胞因子,在先天和适应性免疫反应中发挥关键作用。位于人类 IFN-γ 基因第一内含子中的一个单核苷酸多态性可以影响细胞因子的分泌。因此,我们旨在研究 IFN-γ T/A 基因多态性与宫颈癌风险的关系。

设计

病例对照研究。

地点

印度北方邦。

样本

本研究纳入了 200 例经组织学证实的宫颈癌患者和年龄、种族匹配的 230 例健康对照者。

方法

采用扩增受阻突变系统法对 IFN-γ 双等位基因+874(T/A)多态性进行基因分型。

主要观察指标

低产 IFN-γ+874 AA 基因型与宫颈癌风险增加相关,且在烟草使用者中进一步增加了风险。

结果

低产 IFN-γ 的 IFN-γ AA 基因型与宫颈癌风险增加相关(OR=2.43,P=0.003)。等位基因 A 使宫颈癌的风险增加 1.54 倍(OR=1.54,P=0.002)。AA 基因型与宫颈癌的高分期(III+IV 期)具有统计学显著的风险(OR=4.99,P=0.001)。在烟草使用者中,AA 基因型使宫颈癌的易感性显著增加(OR=5.08,P=0.010)。

结论

由于印度北方邦的种族差异,IFN-γ+874 AA 基因型的变异可能代表了宫颈癌风险以及其他疾病的重要易感生物标志物,需要进一步研究。

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