Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh.
Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh.
Int Immunopharmacol. 2021 Jan;90:107131. doi: 10.1016/j.intimp.2020.107131. Epub 2020 Nov 10.
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.
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).
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) and GAG haplotypes (p = 4.72x10) 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.
Our results conclude that rs16944 (IL1β), rs1801275 (IL4R), and rs1800797 (IL6) polymorphisms are associated with cervical cancer in Bangladeshi women.
宫颈癌（CC）是发展中国家女性癌症相关死亡的主要原因。在孟加拉国，它是女性第二大恶性肿瘤，无论是在发病率还是死亡率方面都是如此。我们目前的研究旨在探讨 IL1β（rs16944）、IL4R（rs1801275）和 IL6（rs1800797）基因多态性与宫颈癌易感性的关系。
本病例对照研究在 252 名宫颈癌患者和 228 名健康志愿者中进行，使用四引物扩增受阻突变系统-聚合酶链反应（ARMS-PCR）。
在 rs16944 多态性方面，GG 基因型（OR=2.10，95%CI=1.24-3.56）、显性模型（OR=1.71，95%CI=1.11-2.63）、隐性模型（OR=1.54，95%CI=1.01-2.35）和 G 等位基因（OR=1.30，95%CI=1.005-1.68）与宫颈癌风险增加显著相关。其中，GG 基因型和显性模型在经过 Bonferroni 校正后仍然具有显著性（p<0.017）。对于 rs1801275 多态性，GG 基因型（OR=2.66，95%CI=1.49-4.75）、显性模型（OR=1.49，95%CI=1.04-2.14）、隐性模型（OR=2.45，95%CI=1.40-4.27）和 G 等位基因（OR=1.59，95%CI=1.21-2.10）显著增加了宫颈癌的风险，但在经过 Bonferroni 校正后，显性模型的显著性不存在。rs1800797 变体在所有遗传模型中均显示出显著增加的风险，包括 AG 基因型（OR=8.13，95%CI=5.27-12.55）、AA 基因型（OR=9.86，95%CI=2.76-35.21）、显性模型（OR=8.25，95%CI=5.40-12.60）、隐性模型（OR=4.41，95%CI=1.25-15.56）和 A 等位基因（OR=4.99，95%CI=3.49-7.13），并且除了隐性模型外，其他模型的显著性均与 Bonferroni 校正一致。单体型分析表明 GAA（p=5.15x10）和 GAG 单体型（p=4.72x10）显著降低了 CC 的风险，而 AAA（p=3.89x10-9）、AAG（p=0.0003）、AGA（p=3.98x10-5）和 AGG 单体型（p=0.002）显著增加了 CC 的风险。IL1β mRNA 水平上调，这与计算机模拟中的不良预后相关。
我们的研究结果表明，rs16944（IL1β）、rs1801275（IL4R）和 rs1800797（IL6）多态性与孟加拉国女性宫颈癌有关。
