Polymorphic variants INSIG2 rs6726538, HLA-DRB1 rs9272143, and GCNT1P5 rs7780883 contribute to the susceptibility of cervical cancer in the Bangladeshi women

Abstract

Objective: Cervical cancer is a gynecological health problem, affecting nearly 500,000 women each year worldwide. Genome-wide association studies have revealed multiple susceptible genes and their polymorphisms for cervical carcinoma risk. We have carried out this case-control study to investigate the association of INSIG2 rs6726538 (A; T), HLA-DRB1 rs9272143 (T; C), and GCNT1P5 rs7780883 (G; A) with cervical cancer.

Methods: The present study recruited 234 cervical cancer patients as cases and 212 healthy females as controls. We have applied the tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) method for genotyping.

Results: The SNP rs6726538 was significantly associated with increased risk of cervical cancer in all genetic models (AT vs. AA: OR = 3.30, 95% CI = 2.19-4.97, p < 0.0001; TT vs. AA: OR = 8.72, 95% CI = 3.87-19.7, p < 0.0001; AT+TT vs. AA: OR = 3.87, 95% CI = 2.61-5.73, p < 0.0001; T vs. A: OR = 2.97, 95% CI = 2.20-4.01, p < 0.0001) except the recessive model which showed a significantly reduced risk (TT vs. AA+AT: OR = 0.20, 95% CI = 0.09-0.44, p = 0.0001). rs9272143 showed significantly reduced risk for the additive model 1, dominant model, and allelic model (TC vs. TT: OR = 0.46, 95% CI = 0.31-0.70, p = 0.0004; TC+CC vs. TT: OR = 0.47 95% CI = 0.32-0.70, p = 0.0002; C vs. T: OR = 0.56, 95% CI = 0.40-0.78, p = 0.0006, respectively). The third variant, rs7780883, was significantly associated with increased risk in additive model 2, dominant, and allelic models (AA vs. GG: OR = 5.08, 95% CI = 2.45-10.5, p < 0.0001; GA+AA vs. GG: OR = 1.54, 95% CI = 1.06-2.24, p = 0.0237; A vs. G: OR = 1.88, 95% CI = 1.34-2.52, p < 0.0001, consecutively), whereas recessive model reduced the risk of cervical cancer (AA vs. GG+GA: OR = 0.20, 95% CI = 0.09-0.41, p < 0.0001). Other models of these SNPs were not associated with cervical cancer. All significant associations for three SNPs withstand after Bonferroni correction except the additive model 2 of rs7780883.

Conclusion: Our study concludes that INSIG2 rs6726538, HLA-DRB1 rs9272143, and GCNT1P5 rs7780883 polymorphisms may contribute to the development of cervical cancer in the Bangladeshi population.

Keywords: GCNT1P5; HLA-DQB1; HLA-DRB1; INSIG2; T-ARMS-PCR; cervical cancer.