Association of IL-10 GTC haplotype with serum level and HPV infection in the development of cervical carcinoma
- 250 Downloads
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.
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.
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.
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.
KeywordsCervical cancer Human papillomavirus (HPV) Cytokines
We would like to thank Dr. Sudha Salhan, Department of Obstetrics and Gynaecology, Safdarjung Hospital, New Delhi and Dr. Swaraj Batra, Department of Obstetrics and Gynaecology, LNJP Hospital, New Delhi, India for providing clinical samples and valuable feedback for the manuscript. We also would like to thank Dr. Suresh Bhambhani, Division of Cytopathology for pathological analysis of the clinical sample. We would like to thank the patients and their family members too. We would like to thank Dr. Dwaipayan Bharadwaj, CSIR-IGIB, New Delhi for critical evaluation of the manuscript. This work was supported by the core funding of ICPO (ICMR) to MB. PS is grateful to the Indian Council of Medical Research (ICMR), and AK is grateful to the University Grant commission (UGC) for their Senior Research Fellowships.
Conflicts of interest
- 1.Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F: GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11; 2013.Google Scholar
- 3.Zur HH. Papillomavirus infections—a major cause of human cancers. Biochim Biophys Acta. 1996;1288:F55–78.Google Scholar
- 15.Wu Z, Zheng W, Xu J, Sun F, Chen H, Li P, Chen S, Shen M, Zhang W, You X, Wu Q, Zhang F, Li Y: IL10 polymorphisms associated with Behcet's disease in Chinese Han. Hum Immunol 2013.Google Scholar
- 17.Zou L, Wang L, Gong X, Zhao H, Jiang A, Zheng S: The association between three promoter polymorphisms of IL-10 and inflammatory bowel diseases (IBD): A meta-analysis. Autoimmunity 2013.Google Scholar
- 21.Sambrook Ra: Molecular Cloninig: A laboratory manual.; Cold Spring Harbor Laboratory Press 3, 2001.Google Scholar
- 22.Manos MM, Ting Y, Wright DK, Lewis AJ, Broker TR, Wolinski SM. Use of polymerase chain reaction amplification for the detection of genital human papillomaviruses. Cancer Cells. 1989;7:pp 209–14.Google Scholar
- 32.Chagas BS, Gurgel AP, da Cruz HL, Amaral CM, Cardoso MV, Silva Neto JC, et al. An interleukin-10 gene polymorphism associated with the development of cervical lesions in women infected with Human Papillomavirus and using oral contraceptives. Infect Genet Evol. 2013;19:32–7.CrossRefPubMedGoogle Scholar
- 38.Torres-Poveda K, Burguete-Garcia AI, Cruz M, Martinez-Nava GA, Bahena-Roman M, Ortiz-Flores E, et al. The SNP at -592 of human IL-10 gene is associated with serum IL-10 levels and increased risk for human papillomavirus cervical lesion development. Infect Agent Cancer. 2012;7:32.CrossRefPubMedPubMedCentralGoogle Scholar