Department of Pharmacy, Noakhali Science and Technology University, Noakhali, Bangladesh.
Department of Pharmacy, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh.
Cancer Med. 2021 Mar;10(5):1829-1838. doi: 10.1002/cam4.3782. Epub 2021 Feb 14.
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.
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.
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.
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.
宫颈癌是一个妇科健康问题，每年在全球范围内影响近 50 万名女性。全基因组关联研究已经揭示了多个易感基因及其多态性与宫颈癌风险相关。我们进行了这项病例对照研究，以调查 INSIG2 rs6726538（A；T）、HLA-DRB1 rs9272143（T；C）和 GCNT1P5 rs7780883（G；A）与宫颈癌的关联。
本研究招募了 234 名宫颈癌患者作为病例组和 212 名健康女性作为对照组。我们应用四引物扩增受阻突变系统聚合酶链反应（T-ARMS-PCR）方法进行基因分型。
在所有遗传模型中，SNP rs6726538 均与宫颈癌风险增加显著相关（AT 与 AA：OR=3.30，95%CI=2.19-4.97，p<0.0001；TT 与 AA：OR=8.72，95%CI=3.87-19.7，p<0.0001；AT+TT 与 AA：OR=3.87，95%CI=2.61-5.73，p<0.0001；T 与 A：OR=2.97，95%CI=2.20-4.01，p<0.0001），除了隐性模型显示出显著降低的风险（TT 与 AA+AT：OR=0.20，95%CI=0.09-0.44，p=0.0001）。rs9272143 在加性模型 1、显性模型和等位基因模型中显示出显著降低的风险（TC 与 TT：OR=0.46，95%CI=0.31-0.70，p=0.0004；TC+CC 与 TT：OR=0.47 95%CI=0.32-0.70，p=0.0002；C 与 T：OR=0.56，95%CI=0.40-0.78，p=0.0006）。第三个变体 rs7780883 与加性模型 2、显性和等位基因模型中的风险增加显著相关（AA 与 GG：OR=5.08，95%CI=2.45-10.5，p<0.0001；GA+AA 与 GG：OR=1.54，95%CI=1.06-2.24，p=0.0237；A 与 G：OR=1.88，95%CI=1.34-2.52，p<0.0001），而隐性模型降低了宫颈癌的风险（AA 与 GG+GA：OR=0.20，95%CI=0.09-0.41，p<0.0001）。这些 SNP 的其他模型与宫颈癌无关。除了 rs7780883 的加性模型 2 外，所有这些 SNP 的显著关联都在 Bonferroni 校正后仍然存在。
我们的研究得出结论，INSIG2 rs6726538、HLA-DRB1 rs9272143 和 GCNT1P5 rs7780883 多态性可能导致孟加拉国人群宫颈癌的发生。
