Genetic Variants in Interleukin-10 Gene Association with Susceptibility and Cervical Cancer Development: A Case Control Study

Abstract

Objectives Cervical cancer (CC) is one of the most destructive disease caused by persistent HPV infection which affects women worldwide, especially in developing countries. The genetic basis of host immune response especially cytokine function has been shown to influence CC susceptibility. Studies have demonstrated that IL-10 gene polymorphism have been associated with numerous malignancies, but in context to CC results were inconclusive. Though, aim of our study to investigate the association between IL-10 -1082A/G and -819C/T promoter polymorphism and CC susceptibility.
Material and Methods This study comprised 192 women with CC and 200 controls. HPV detection was done by RT-PCR and genotyping was assessed through PCR-RFLP method. Serum concentration of IL-10 measured by ELISA.
Results Women with AG and AG+GG genotypes of IL-10 -1082A/G had two-fold increased risk of CC [OR, 2.35 (95% CI, 1.54-3.58), p = 0.005], [OR, 2.03 (95% CI, 1.36-3.04), p = 0.0005] compared to controls. Women with G allele of -1082A/G polymorphism had linked with CC susceptibility [OR, 1.39 (95% CI, 1.02-1.88), p = 0.036] compared to controls. No significant difference was found between patients and controls in the genotype or allele frequencies of IL-10 -819C/T polymorphism [OR, 1.00 (95% CI, 0.63-1.58), p = 0.99]. The level of serum concentration of IL-10 was significantly higher in cases compared to controls.
Conclusion These findings help to understand that polymorphism of IL-10 -1082A/G gene is associated with increased risk of CC development and can serve as a marker of genetic susceptibility to CC.

Keywords

human papillomavirus / cervical cancer / gene polymorphism

References

[1] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A.Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(06): 394-424

[2] Sadri Nahand J, Moghoofei M, Salmaninejad A.et al.Pathogenic role of exosomes and microRNAs in HPV-mediated inflammation and cervical cancer: a review. Int J Cancer 2020; 146(02): 305-320

[3] Ghasemi F, Shafiee M, Banikazemi Z.et al.Curcumin inhibits NF-kB and Wnt/β-catenin pathways in cervical cancer cells. Pathol Res Pract 2019; 215(10): 152556

[4] Nahand JS, Taghizadeh-Boroujeni S, Karimzadeh M.et al.microRNAs: new prognostic, diagnostic, and therapeutic biomarkers in cervical cancer. J Cell Physiol 2019; 234(10): 17064-17099

[5] Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A.Global cancer statistics, 2012. CA Cancer J Clin 2015; 65(02): 87-108

[6] Cohen PA, Jhingran A, Oaknin A, Denny L.Cervical cancer. Lancet 2019; 393(10167): 169-182

[7] Pratap P, Raza ST, Zaidi G, Charles MR, Kunwar S.Molecular biology of human papillomavirus, cervical carcinoma and its management. Canadian J Clin Nutr 2021; 9(01): 71-88

[8] Chen X, Jiang J, Shen H, Hu Z.Genetic susceptibility of cervical cancer. J Biomed Res 2011; 25(03): 155-164

[9] Kessler TA.Cervical cancer: prevention and early detection. Semin Oncol Nurs 2017; 33(02): 172-183

[10] Kjellberg L, Hallmans G, Ahren AM.et al.Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection. Br J Cancer 2000; 82(07): 1332-1338

[11] Martínez-Nava GA, Fernández-Niño JA, Madrid-Marina V, Torres-Poveda K.Cervical cancer genetic susceptibility: a systematic review and meta-analyses of recent evidence. PLoS One 2016; 11(07): e0157344

[12] Magnusson PK, Lichtenstein P, Gyllensten UB.Heritability of cervical tumours. Int J Cancer 2000; 88(05): 698-701

[13] Mehta AM, Mooij M, Branković I, Ouburg S, Morré SA, Jordanova ES.Cervical carcinogenesis and immune response gene polymorphisms: a review. J Immunol Res 2017; 2017: 8913860

[14] zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2002; 2(05): 342-350

[15] Sasagawa T, Takagi H, Makinoda S.Immune responses against human papillomavirus (HPV) infection and evasion of host defense in cervical cancer. J Infect Chemother 2012; 18(06): 807-815

[16] Gao J, Wei L, Fu R.et al.Association of Interleukin-10 polymorphisms (rs1800872, rs1800871, and rs1800896) with Predisposition to IgA nephropathy in a Chinese Han population: a case-control study. Kidney Blood Press Res 2017; 42(01): 89-98

[17] Ding Q, Shi Y, Fan B.et al.The interleukin-10 promoter polymorphism rs1800872 (-592C>A), contributes to cancer susceptibility: meta-analysis of 16,785 cases and 19,713 controls. PLoS One 2013; 8(02): e57246

[18] Dai ZJ, Wang XJ, Zhao Y.et al.Effects of interleukin-10 polymorphisms (rs1800896, rs1800871, and rs1800872) on breast cancer risk: evidence from an updated meta-analysis. Genet Test Mol Biomarkers 2014; 18(06): 439-445

[19] Mohammadi S, Saghaeian Jazi M, Zare Ebrahimabad M.et al.Interleukin 10 gene promoter polymorphisms (rs1800896, rs1800871 and rs1800872) and haplotypes are associated with the activity of systemic lupus erythematosus and IL10 levels in an Iranian population. Int J Immunogenet 2019; 46(01): 20-30

[20] Holster A, Nuolivirta K, Törmänen S.et al.Interleukin-10 gene polymorphism rs1800896 is associated with post-bronchiolitis asthma at 11-13 years of age. Acta Paediatr 2019; 108(11): 2064-2069

[21] Du GH, Wang JK, Richards JR, Wang JJ.Genetic polymorphisms in tumor necrosis factor alpha and interleukin-10 are associated with an increased risk of cervical cancer. Int Immunopharmacol 2019; 66: 154-161

[22] Bai CY, Shi XY, He J, Xue J, Feng Y.Association between IL-10 genetic variations and cervical cancer susceptibility in a Chinese population. Genet Mol Res 2016;15(03):

[23] Ni J, Ye Y, Teng F, Wu Q.Interleukin 10 polymorphisms and cervical cancer risk: a meta-analysis. Int J Gynecol Cancer 2013; 23(01): 126-133

[24] Singhal P, Kumar A, Bharadwaj S, Hussain S, Bharadwaj M.Association of IL-10 GTC haplotype with serum level and HPV infection in the development of cervical carcinoma. Tumour Biol 2015; 36(04): 2287-2298

[25] Torres-Poveda K, Burguete-García AI, Cruz M.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(01): 32

[26] Zoodsma M, Nolte IM, Schipper M.et al.Interleukin-10 and Fas polymorphisms and susceptibility for (pre)neoplastic cervical disease. Int J Gynecol Cancer 2005; 15(Suppl. 03): 282-290

[27] Chagas BS, Gurgel AP, da Cruz HL. 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: 32-37

[28] Matsumoto K, Oki A, Satoh T.et al.Interleukin-10 -1082 gene polymorphism and susceptibility to cervical cancer among Japanese women. Jpn J Clin Oncol 2010; 40(11): 1113-1116

[29] Huang T, Shu Y, Cai YD.Genetic differences among ethnic groups. BMC Genomics 2015; 16: 1093

[30] Sreeja L, Syamala V, Raveendran PB, Santhi S, Madhavan J, Ankathil R. p53 Arg72Pro polymorphism predicts survival outcome in lung cancer patients in Indian population. Cancer Invest 2008; 26(01): 41-46

[31] Zhang L, Jiang Y, Lu X.et al.Genomic characterization of cervical cancer based on human papillomavirus status. Gynecol Oncol 2019; 152(03): 629-637

[32] Bahrami A, Hasanzadeh M, Shahidsales S.et al.Genetic susceptibility in cervical cancer: from bench to bedside. J Cell Physiol 2018; 233(03): 1929-1939

[33] Shafabakhsh R, Reiter RJ, Mirzaei H, Teymoordash SN, Asemi Z.Melatonin: a new inhibitor agent for cervical cancer treatment. J Cell Physiol 2019; 234(12): 21670-21682

[34] Fernandes AP, Gonçalves MA, Simões RT, Mendes-Junior CT, Duarte G, Donadi EA.A pilot case-control association study of cytokine polymorphisms in Brazilian women presenting with HPV-related cervical lesions. Eur J Obstet Gynecol Reprod Biol 2008; 140(02): 241-244

[35] Sharma A, Rajappa M, Saxena A, Sharma M.Cytokine profile in Indian women with cervical intraepithelial neoplasia and cancer cervix. Int J Gynecol Cancer 2007; 17(04): 879-885

[36] Willeke P, Gaubitz M, Schotte H, Becker H, Domschke W, Schlüter B.The role of interleukin-10 promoter polymorphisms in primary Sjogren's syndrome. Scand J Rheumatol 2008; 37(04): 293-299

[37] Ouma C, Davenport GC, Were T.et al.Haplotypes of IL-10 promoter variants are associated with susceptibility to severe malarial anemia and functional changes in IL-10 production. Hum Genet 2008; 124(05): 515-524

[38] Niu YM, Du XY, Cai HX.et al.Increased risks between Interleukin-10 gene polymorphisms and haplotype and head and neck cancer: a meta-analysis. Sci Rep 2015; 5: 17149

[39] de Oliveira JG, Rossi AF, Nizato DM.et al. Influence of functional polymorphisms in TNF-α, IL-8, and IL-10 cytokine genes on mRNA expression levels and risk of gastric cancer. Tumour Biol 2015; 36(12): 9159-9170

[40] Hiroki CH, Amarante MK, Petenuci DL.et al.IL-10 gene polymorphism and influence of chemotherapy on cytokine plasma levels in childhood acute lymphoblastic leukemia patients: IL-10 polymorphism and plasma levels in leukemia patients. Blood Cells Mol Dis 2015; 55(02): 168-172

[41] Chagas BS, Lima RCP, Paiva Júnior SSL.et al.Significant association between IL10-1082/-819 and TNF-308 haplotypes and the susceptibility to cervical carcinogenesis in women infected by Human papillomavirus. Cytokine 2019; 113: 99-104

[42] Hardikar S, Johnson LG, Malkki M.et al.A population-based case-control study of genetic variation in cytokine genes associated with risk of cervical and vulvar cancers. Gynecol Oncol 2015; 139(01): 90-96

[43] Netea MG, Wijmenga C, O'Neill LA. Genetic variation in Toll-like receptors and disease susceptibility. Nat Immunol 2012; 13(06): 535-542

[44] Lettre G, Rioux JD.Autoimmune diseases: insights from genome-wide association studies. Hum Mol Genet 2008; 17(R2): R116-R121

[45] Cerhan JR, Ansell SM, Fredericksen ZS.et al.Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma. Blood 2007; 110(13): 4455-4463

[46] Hamidullah CB, Changkija B, Konwar R.Role of interleukin-10 in breast cancer. Breast Cancer Res Treat 2012; 133(01): 11-21

[47] Mocellin S, Marincola FM, Young HA.Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol 2005; 78(05): 1043-1051

[48] Wang Y, Liu XH, Li YH, Li O.The paradox of IL-10-mediated modulation in cervical cancer. Biomed Rep 2013; 1(03): 347-351

[49] Stanczuk GA, Sibanda EN, Perrey C.et al.Cancer of the uterine cervix may be significantly associated with a gene polymorphism coding for increased IL-10 production. Int J Cancer 2001; 94(06): 792-794

RIGHTS & PERMISSIONS

2022 Global Medical Genetics