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白细胞介素-10基因GTC单倍型与宫颈癌发生发展过程中血清水平及人乳头瘤病毒感染的相关性

Association of IL-10 GTC haplotype with serum level and HPV infection in the development of cervical carcinoma.

作者信息

Singhal Pallavi, Kumar Anoop, Bharadwaj Soham, Hussain Showket, Bharadwaj Mausumi

机构信息

Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector 39, Noida, Uttar Pradesh, 201301, India.

出版信息

Tumour Biol. 2015 Apr;36(4):2287-98. doi: 10.1007/s13277-014-2836-6. Epub 2014 Nov 21.

Abstract

AIM

Cervical cancer is the most common gynecological malignancy in the developing countries like India. In addition to human papillomavirus (HPV) infection, host genetic factors play an important role in viral persistence and neoplastic growth. IL-10, a multifunctional cytokine, plays an active role to promote tumor growth in the presence of HPV. The present study aims to find out the impact of IL-10 promoter polymorphisms at -1082A/G (rs1800896), -819C/T (rs1800872), and -592C/A (rs1800871) sites along with IL-10 production and HPV infection in the progression of cervical cancer.

METHODS

We have genotyped a total of 506 subjects, 256 cases (208 cervical cancer + 48 precancer), and 250 healthy controls by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method followed by sequencing. IL-10 serum concentration was measured by enzyme-linked immunosorbent assay.

RESULTS

The frequency of IL-10 -592 variant genotype (AA) was found significantly reduced in cases as compare to controls while -1082 variant genotype (GG) was found ~4-fold higher risk of cervical cancer (p = <0.0001, OR = 3.667, 95% CI = 2.329-5.773). On construction of haplotypes, GTC haplotype was emerged as a major risk haplotype while ACA haplotype was seemed as a marker for precancerous lesions. IL-10 serum concentration was observed higher in HPV-infected precancer and cancer cases. GTC haplotype was found to be coupled with higher serum concentration of IL-10 and HPV infection.

CONCLUSION

IL-10 polymorphisms play a role in cervical cancer development and that GTC haplotype, which is closely related to its serum concentration, maybe a useful biomarker for HPV-mediated cervical cancer.

摘要

目的

在印度等发展中国家,宫颈癌是最常见的妇科恶性肿瘤。除人乳头瘤病毒(HPV)感染外,宿主遗传因素在病毒持续存在和肿瘤生长中起重要作用。白细胞介素-10(IL-10)是一种多功能细胞因子,在HPV存在的情况下对促进肿瘤生长发挥积极作用。本研究旨在探究IL-10启动子在-1082A/G(rs1800896)、-819C/T(rs1800872)和-592C/A(rs1800871)位点的多态性以及IL-10产生和HPV感染在宫颈癌进展中的影响。

方法

我们采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法随后进行测序,对总共506名受试者进行基因分型,其中256例为病例(208例宫颈癌+48例癌前病变),250例为健康对照。通过酶联免疫吸附测定法测量IL-10血清浓度。

结果

与对照组相比,病例组中IL-10 -592变异基因型(AA)的频率显著降低,而-1082变异基因型(GG)患宫颈癌的风险高出约4倍(p =<0.0001,OR = 3.667,95% CI = 2.329 - 5.773)。构建单倍型时,GTC单倍型成为主要风险单倍型,而ACA单倍型似乎是癌前病变的标志物。在HPV感染的癌前病变和癌症病例中观察到IL-10血清浓度较高。发现GTC单倍型与较高的IL-10血清浓度和HPV感染相关。

结论

IL-10多态性在宫颈癌发展中起作用,与其血清浓度密切相关的GTC单倍型可能是HPV介导的宫颈癌的有用生物标志物。

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