Wang Yao, Liu Yang, Li Zhongyi, Yan Xiumin, Huang Chuican, Ye Xingguang, Sun Xiuhong, Qin Shuang, Zhong Xingming, Zeng Chengli, Liu Dandan, Zou Xiaoqian, Liu Yumei, Wu Jing, Wen Zihao, Yang Guang, Jing Chunxia, Wei Xiangcai
1 Department of Epidemiology, School of Medicine, Jinan University , Guangzhou, China .
2 Guangdong Women and Children Hospital , Guangzhou, China .
Genet Test Mol Biomarkers. 2018 Sep;22(9):509-517. doi: 10.1089/gtmb.2018.0097. Epub 2018 Sep 6.
The occurrence of cervical cancer is a complex process, for which human papillomavirus (HPV) infection is a risk factor, although not all women infected with HPV will develop the disease. Knockout of mammalian lung metastasis associated transcript 1 (MALAT1) is associated with increased risk for several cancer types, whereas the long non-coding RNA (lncRNA) THRIL is essential for induction of tumor necrosis factor-α expression, which plays important roles in HPV infection.
To investigate the effects of polymorphisms in the lncRNAs MALAT1 and THRIL on the susceptibility to precancerous cervical lesions, 12 single nucleotide polymorphisms (SNPs) were analyzed from 164 cervical precancerous lesion cases and 428 controls. Gene-gene and gene-environment interactions and haplotype associations were also evaluated.
We found a significantly decreased risk of precancerous cervical lesions for the THRIL rs7133268 AG genotype (odds ratio adjusted = 0.63, 95% confidence interval: 0.42-0.94, p = 0.025). Multifactor dimensionality reduction analysis identified a significant two-locus interaction model involved in HPV infection and THRIL rs7133268 (training balanced accuracy = 0.6957, testing balanced accuracy = 0.6948, cross-validation consistency = 10/10, p = 0.0046). Other SNPs, including the two identified for MALAT1, were not significantly related to the risk of precancerous cervical lesions.
Our results suggest that the rs7133268 polymorphism of the lncRNA THRIL gene can reduce the genetic susceptibility of precancerous cervical lesions and in turn reduce the risk of HPV infection.
宫颈癌的发生是一个复杂的过程，人乳头瘤病毒（HPV）感染是其危险因素，尽管并非所有感染HPV的女性都会发病。哺乳动物肺转移相关转录本1（MALAT1）的敲除与多种癌症类型的风险增加相关，而长链非编码RNA（lncRNA）THRIL对于诱导肿瘤坏死因子-α表达至关重要，肿瘤坏死因子-α在HPV感染中发挥重要作用。
为了研究lncRNAs MALAT1和THRIL中的多态性对癌前宫颈病变易感性的影响，对164例宫颈病变癌前病例和428例对照进行了12个单核苷酸多态性（SNP）分析。还评估了基因-基因和基因-环境相互作用以及单倍型关联。
我们发现THRIL rs7133268 AG基因型的癌前宫颈病变风险显著降低（调整后的优势比=0.63，95%置信区间：0.42-0.94，p=0.025）。多因素降维分析确定了一个涉及HPV感染和THRIL rs7133268的显著两位点相互作用模型（训练平衡准确率=0.6957，测试平衡准确率=0.6948，交叉验证一致性=10/10，p=0.0046）。其他SNP，包括为MALAT1鉴定的两个SNP，与癌前宫颈病变风险无显著相关性。
我们的结果表明，lncRNA THRIL基因的rs7133268多态性可降低癌前宫颈病变的遗传易感性，进而降低HPV感染风险。
