Association study of IL10 gene polymorphisms (rs1800872 and rs1800896) with cervical cancer in the Bangladeshi women

Anamika Datta; Fatema Tuz Zahora; Md Abdul Aziz; Mohammad Sarowar Uddin; Mahmuda Ferdous; Md Shalahuddin Millat; Md Shahid Sarwar; Md Abdul Barek; Sarah Jafrin; Shamsun Nahar; Mohammad Safiqul Islam

doi:10.1016/j.intimp.2020.107091

Association study of IL10 gene polymorphisms (rs1800872 and rs1800896) with cervical cancer in the Bangladeshi women

Int Immunopharmacol. 2020 Dec;89(Pt B):107091. doi: 10.1016/j.intimp.2020.107091. Epub 2020 Oct 16.

Affiliations

¹ Department of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali 3814, Bangladesh.
² Department of Oncology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka 1000, Bangladesh.
³ Department of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali 3814, Bangladesh. Electronic address: research_safiq@yahoo.com.

PMID: 33069925
DOI: 10.1016/j.intimp.2020.107091

Abstract

Objective: Cervical cancer is one of the most destructive diseases among females worldwide, especially in developing countries. Interleukin-10 (IL10) is a multifunctional cytokine, and polymorphisms in the IL10 gene have been identified in multiple malignancies. However, no prior studies were conducted to determine the association of IL10 polymorphisms (rs1800872 and rs1800896) with cervical cancer patients in Bangladesh.

Methods: This case-control study was carried out on 240 cervical cancer patients and 204 healthy volunteers. Genotyping was performed using the tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR).

Results: In the case of rs1800872, CA and AA genotypes significantly increased the risk of cervical cancer (OR = 1.59, 95% CI = 1.01-2.49, p = 0.043; OR = 2.75, 95% CI = 1.53-4.93, p = 0.0007, respectively) but the significance did not exist for CA genotype after Bonferroni correction (p < 0.025). An increased risk was also observed for the dominant model, recessive model, and allele model (A vs. C) of rs1800872 (dominant model: OR = 1.83, 95% CI = 1.18-2.80, p = 0.006; recessive model: OR = 2.00, 95% CI = 1.22-3.29, p = 0.006; allele model: OR = 1.55, 95% CI = 1.19-2.03, p = 0.001) which remained significant after the correction of Bonferroni. For rs1800896, only GG genotype and recessive model showed increased risk for cervical cancer (GG vs. AA: OR = 3.48, 95% CI = 1.46-8.31, p = 0.005; recessive model: OR = 3.57, 95% CI = 1.52-8.38, p = 0.003). These associations were statistically significant, and the significance existed after Bonferroni correction. Haplotype analysis revealed that AA haplotype significantly increased the risk (OR = 1.56, p = 0.001) whereas, CA haplotype significantly lowered the risk (OR = 0.42, p = 2.42x10^-8), and both rs1800872 and rs1800896 are strongly in linkage disequilibrium (D'=1, r² = 0.333). Moreover, the IL10 mRNA level was found up-regulated in silico in cervical squamous cell carcinoma tissues compared to healthy tissues (p = 1.11x10^-16).

Conclusion: Our study suggests that rs1800872 and rs1800896 polymorphisms of IL10 gene are associated with cervical cancer in Bangladeshi females.

Keywords: Cervical cancer; Genetic polymorphism; IL10; Tetra-primer ARMS-PCR.

MeSH terms

Adult
Alleles
Bangladesh / epidemiology
Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / metabolism
Case-Control Studies
Databases, Genetic
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Haplotypes
Humans
Interleukin-10 / genetics*
Interleukin-10 / metabolism*
Middle Aged
Polymorphism, Single Nucleotide*
Uterine Cervical Neoplasms / genetics*
Uterine Cervical Neoplasms / metabolism*

Substances

IL10 protein, human
Interleukin-10