Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Mol Biol Rep. 2011 Oct;38(7):4715-21. doi: 10.1007/s11033-010-0607-z. Epub 2010 Dec 5.
Cervical cancer is emerging as a leading cause of morbidity and mortality in women worldwide. Toll-like Receptor (TLR) gene polymorphisms may contribute to subsequent inter-individual variability in cancer susceptibility. The present study aimed to identify the role of TLR 3 (c.1377C/T) [rs3775290] and TLR 9 (G2848A) [rs352140] gene polymorphisms in the risk of developing cervical cancer in North India. Peripheral blood samples were collected from 200 histopathologically confirmed cervical cancer patients from North India and 200 unrelated, cancer-free, age-matched healthy female controls of similar ethnicity. Genomic DNA was extracted using the salting-out method, and genotyped for TLR 3 and TLR 9 using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Our data demonstrated a lack of association between TLR 3 (c.1377C/T) and TLR 9 (G2848A) gene polymorphisms and the risk of developing cervical cancer. TLR 3 CT + TT was marginally associated (P = 0.061; age-adjusted OR = 1.46; 95% CI = 0.98-2.16) with cervical cancer susceptibility. The AA genotype of TLR 9 showed borderline significance (P = 0.053) conferring a marginal increased risk (OR = 2.63, 95%CI = 0.99-7.01) for advanced cancer stages (III + IV). Further, TLR 3 and 9 polymorphisms did not have a significant role in modulation of risk due to tobacco usage in cervical cancer patients. Our study suggests only marginal role of TLR 3 and 9 gene polymorphisms in cervical cancer susceptibility in North India; however, future studies in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in cervical cancer etiology in women worldwide.
宫颈癌正在成为全球女性发病率和死亡率上升的主要原因。 Toll 样受体（TLR）基因多态性可能导致癌症易感性的个体间差异。本研究旨在确定 TLR3（c.1377C/T）[rs3775290]和 TLR9（G2848A）[rs352140]基因多态性在印度北部宫颈癌发病风险中的作用。采集了 200 名经组织病理学证实的宫颈癌患者和 200 名来自印度北部、无癌、年龄匹配、具有相似种族背景的健康女性对照者的外周血样。采用盐析法提取基因组 DNA，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对 TLR3 和 TLR9 进行基因分型。我们的数据表明，TLR3（c.1377C/T）和 TLR9（G2848A）基因多态性与宫颈癌发病风险之间没有关联。TLR3 CT+TT 与宫颈癌易感性呈边缘相关（P=0.061；年龄校正 OR=1.46；95%CI=0.98-2.16）。TLR9 的 AA 基因型具有显著意义（P=0.053），提示其对晚期癌症（III+IV 期）具有边际增加的风险（OR=2.63，95%CI=0.99-7.01）。此外，TLR3 和 9 多态性在宫颈癌患者吸烟对风险的调节中没有显著作用。本研究表明，TLR3 和 9 基因多态性在印度北部宫颈癌易感性中仅起次要作用；然而，在不同种族人群中的进一步研究可能会提供更多有关先天免疫在全球女性宫颈癌发病机制中的综合作用。
