IL10 基因多态性（rs1800872 和 rs1800896）与孟加拉国女性宫颈癌的关联研究。
Association study of IL10 gene polymorphisms (rs1800872 and rs1800896) with cervical cancer in the Bangladeshi women.
机构信息
Department of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali 3814, Bangladesh.
Department of Oncology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka 1000, Bangladesh.
出版信息
Int Immunopharmacol. 2020 Dec;89(Pt B):107091. doi: 10.1016/j.intimp.2020.107091. Epub 2020 Oct 16.
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), and both rs1800872 and rs1800896 are strongly in linkage disequilibrium (D'=1, r = 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).
CONCLUSION
Our study suggests that rs1800872 and rs1800896 polymorphisms of IL10 gene are associated with cervical cancer in Bangladeshi females.
目的
宫颈癌是全球女性中最具破坏性的疾病之一，尤其在发展中国家。白细胞介素 10（IL10）是一种多功能细胞因子，其基因中的多态性已在多种恶性肿瘤中被发现。然而，以前没有研究确定 IL10 基因多态性（rs1800872 和 rs1800896）与孟加拉国宫颈癌患者之间的关系。
方法
本病例对照研究共纳入 240 例宫颈癌患者和 204 名健康志愿者。采用四引物扩增受阻突变系统聚合酶链反应（ARMS-PCR）进行基因分型。
结果
在 rs1800872 中，CA 和 AA 基因型显著增加了宫颈癌的风险（OR=1.59，95%CI=1.01-2.49，p=0.043；OR=2.75，95%CI=1.53-4.93，p=0.0007），但经 Bonferroni 校正后 CA 基因型的显著性丧失（p<0.025）。在 rs1800872 的显性模型、隐性模型和等位基因模型（A 对 C）中也观察到了风险增加（显性模型：OR=1.83，95%CI=1.18-2.80，p=0.006；隐性模型：OR=2.00，95%CI=1.22-3.29，p=0.006；等位基因模型：OR=1.55，95%CI=1.19-2.03，p=0.001），经 Bonferroni 校正后仍具有显著性。对于 rs1800896，只有 GG 基因型和隐性模型显示宫颈癌风险增加（GG 对 AA：OR=3.48，95%CI=1.46-8.31，p=0.005；隐性模型：OR=3.57，95%CI=1.52-8.38，p=0.003）。这些关联具有统计学意义，且经 Bonferroni 校正后仍具有显著性。单体型分析显示，AA 单体型显著增加了风险（OR=1.56，p=0.001），而 CA 单体型显著降低了风险（OR=0.42，p=2.42x10），且 rs1800872 和 rs1800896 之间存在强烈的连锁不平衡（D'=1，r=0.333）。此外，与健康组织相比，在宫颈癌鳞状细胞癌组织中发现 IL10 mRNA 水平显著上调（p=1.11x10）。
结论
本研究提示 IL10 基因的 rs1800872 和 rs1800896 多态性与孟加拉国女性宫颈癌有关。
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