Detection of association of IL1β, IL4R, and IL6 gene polymorphisms with cervical cancer in the Bangladeshi women by tetra-primer ARMS-PCR method

Abstract

Background: Cervical cancer (CC) is the main cause of cancer-related deaths among women in developing countries. It is the second leading female malignancy in Bangladesh in terms of incidence and mortality. Our present study aimed to investigate the association of IL1β (rs16944), IL4R (rs1801275), and IL6 (rs1800797) gene polymorphisms with the susceptibility of cervical cancer.

Materials and methods: This case-control study was conducted on 252 cervical cancer patients and 228 healthy volunteers, using tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR).

Results: In the case of rs16944 polymorphism, GG genotype (OR = 2.10, 95%CI = 1.24-3.56), dominant model (OR = 1.71, 95% CI = 1.11-2.63), recessive model (OR = 1.54, 95% CI = 1.01-2.35), and G allele (OR = 1.30, 95% CI = 1.005-1.68) were significantly associated with increased cervical cancer risk. Among these, GG genotype and dominant model remained significant after the Bonferroni correction (p < 0.017). For rs1801275 polymorphism, GG genotype (OR = 2.66, 95% CI = 1.49-4.75), dominant model (OR = 1.49, 95% CI = 1.04-2.14), recessive model (OR = 2.45, 95% CI = 1.40-4.27), and G allele (OR = 1.59, 95% CI = 1.21-2.10) significantly elevated the risk of cervical cancer but significance did not exist for dominant model after the Bonferroni correction. rs1800797 variant showed significantly increased risk in all genetic models including, AG genotype (OR = 8.13, 95% CI = 5.27-12.55), AA genotype (OR = 9.86, 95% CI = 2.76-35.21), dominant model (OR = 8.25, 95% CI = 5.40-12.60), recessive model (OR = 4.41, 95% CI = 1.25-15.56), and A allele (OR = 4.99, 95% CI = 3.49-7.13) and the significances were consistent with the Bonferroni correction except recessive model. Haplotyping analysis indicates that GAA (p = 5.15x10^-5) and GAG haplotypes (p = 4.72x10^-9) significantly decreased the risk of CC, whereas AAA (p = 3.89x10-9), AAG (p = 0.0003), AGA (p = 3.98x10-5) and AGG haplotypes (p = 0.002) significantly increased the risk of CC. The IL1β mRNA level was up-regulated, which was associated with poor prognosis in silico.

Conclusion: Our results conclude that rs16944 (IL1β), rs1801275 (IL4R), and rs1800797 (IL6) polymorphisms are associated with cervical cancer in Bangladeshi women.

Keywords: Cervical cancer; IL1β; IL4R; IL6; Polymorphism; Proinflammatory cytokines.