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白细胞介素-1受体拮抗剂基因和白细胞介素-1β基因的遗传变异与宫颈癌风险

Genetic variants of interleukin-1RN and interleukin-1beta genes and risk of cervical cancer.

作者信息

Singh H, Sachan R, Goel H, Mittal B

机构信息

Department of Genetics, SGPGIMS, Lucknow, India.

出版信息

BJOG. 2008 Apr;115(5):633-8. doi: 10.1111/j.1471-0528.2007.01655.x.

DOI:10.1111/j.1471-0528.2007.01655.x
PMID:18333945
Abstract

OBJECTIVES

Inflammation plays a major role in pathogenesis of cervical cancer. We planned to study whether polymorphisms in inflammation-related genes, IL-1RN (VNTR) and IL-1beta (-511C/T), are associated with risk of cervical cancer.

DESIGN

Case-control study.

SETTING

Uttar Pradesh state in India.

SAMPLE

One hundred and fifty, histopathologically confirmed cases with cervical cancer and 162 age-, ethnicity-matched, cervical cytology negative, healthy controls were recruited to this study.

METHODS

Genotyping of IL-1RN (VNTR) and IL-1beta (-511C/T) polymorphisms was performed using polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism. Power of study was 80% with type 1 error of 0.05. Haplotypes frequencies were obtained by computer package 'Arlequin'.

MAIN OUTCOME MEASURES

Haplotype IL-1RN2/IL-1betaT is associated with higher risk and of cervical cancer.

RESULTS

IL-1RN genotypes 1/2 and 2/2 were associated with significantly elevated risk of cervical cancer (OR = 3.3; P= 4.9 x 10(-6) and OR = 2.9, P= 0.02). Similarly, TT genotype of IL-1betapolymorphism was significantly higher in cases compared with controls (57.7 versus 38.3%; OR = 2.8; P = 0.012). 2/2 genotype of IL-1RN (OR = 4.8, P = 0.0006) and TT genotype of IL-1beta(OR = 5.2; P = 0.02) were associated with the higher stages (III) of cervical cancer. Haplotypes 1T (IL-1RN1/IL-1betaT) and 2T (IL-1RN2/IL-1betaT) were also significantly associated with higher susceptibility to cervical cancer and its progression. Logistic regression analysis suggests IL-1RN allele 2 and IL-1beta-511T were independently associated with increased risk for cervical cancer.

CONCLUSION

IL-1RN2 and IL-1beta -511T in various combinations of genotypes and haplotypes are associated with higher susceptibility for cervical cancer.

摘要

目的

炎症在宫颈癌发病机制中起主要作用。我们计划研究炎症相关基因IL-1RN(可变数目串联重复序列)和IL-1β(-511C/T)的多态性是否与宫颈癌风险相关。

设计

病例对照研究。

地点

印度北方邦。

样本

招募了150例经组织病理学确诊的宫颈癌病例和162例年龄、种族匹配、宫颈细胞学检查阴性的健康对照者参与本研究。

方法

采用聚合酶链反应(PCR)/PCR限制性片段长度多态性方法对IL-1RN(可变数目串联重复序列)和IL-1β(-511C/T)多态性进行基因分型。研究效能为80%,I类错误为0.05。单倍型频率通过计算机软件“Arlequin”获得。

主要观察指标

单倍型IL-1RN2/IL-1βT与宫颈癌风险较高相关。

结果

IL-1RN基因分型1/2和2/2与宫颈癌风险显著升高相关(比值比[OR]=3.3;P=4.9×10⁻⁶和OR=2.9,P=0.02)。同样,与对照组相比,病例组中IL-1β多态性的TT基因型显著更高(57.7%对38.3%;OR=2.8;P=0.012)。IL-1RN的2/2基因型(OR=4.8,P=0.0006)和IL-1β的TT基因型(OR=5.2;P=0.02)与宫颈癌的较高分期(III期)相关。单倍型1T(IL-1RN1/IL-1βT)和2T(IL-1RN2/IL-1βT)也与宫颈癌易感性及其进展显著相关。逻辑回归分析表明,IL-1RN等位基因2和IL-1β-511T与宫颈癌风险增加独立相关。

结论

IL-1RN2和IL-1β -511T在各种基因型和单倍型组合中与宫颈癌易感性较高相关。

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