Detection of association of IL1ß, IL4R, and IL6 gene polymorphisms with cervical cancer in the Bangladeshi women by tetra-primer ARMS-PCR method.

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 IL1ß (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 IL1ß mRNA level was up-regulated, which was associated with poor prognosis in silico. CONCLUSION: Our results conclude that rs16944 (IL1ß), rs1801275 (IL4R), and rs1800797 (IL6) polymorphisms are associated with cervical cancer in Bangladeshi women.

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

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.