Association of Long Non-Coding RNAs (lncRNAs) ANRIL and MALAT1 Polymorphism with Cervical Cancer

Yueting Yao,1,* Yan Liang,2,* Xudong Dong,3 Shuyuan Liu,1 Shao Zhang,4 Weipeng Liu,1 Yu Li,5 Li Shi,1 Zhiling Yan,4 Yufeng Yao1 1Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, 650118, People’s Republic of China; 2College of Nursing Health Sciences, Yunnan Open University, Kunming, 650223, People’s Republic of China; 3The First People’s Hospital of Yunnan Province & The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, People’s Republic of China; 4Department of Gynaecologic Oncology, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, People’s Republic of China; 5Department of Obstetrics, The First People’s Hospital of Kunming, Kunming, 650011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiling Yan, Department of Gynaecologic Oncology, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, People’s Republic of China, Email yanzhiling2021@126.com Yufeng Yao, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan, 650118, People’s Republic of China, Email yufeng_yao@imbcams.com.cnBackground: Long non-coding RNAs (lncRNAs) and their polymorphisms play crucial roles in the development of different cancers.Methods: Eight single-nucleotide polymorphisms (SNPs) in ANRIL and MALAT1 (rs1333045, rs4977574, rs1333048, and rs10757278 in ANRIL and rs11227209, rs619586, rs664589, and rs3200401 in MALAT1) were enrolled and genotyped in a total of 1248 samples, including 587 patients with cervical cancer (CC) and 661 healthy individuals using in TaqMan assay. The association of these SNPs with CC was then evaluated.Results: Our results showed that the allele and genotype frequencies of rs3200401 in MALAT1 were significantly different between the control and CC groups after Bonferroni correction (P = 0.001 and P = 0.004, respectively), indicating that the C allele is a protective factor against CC (OR = 0.70; 95% CI = 0.57– 0.87). In addition, the allele and genotype frequencies of rs4977574 in ANRIL were significantly different between the control and CC groups after Bonferroni correction (P = 0.004 and P = 0.014, respectively), and the A allele might be a protective factor for CC (OR = 0.80; 95% CI = 0.68– 0.93). For subgroup analysis, the alleles of rs3200401 in MALAT1 showed significant differences between the control and adenocarcinoma (AC) and control and squamous cell carcinoma (SCC) groups (P = 0.005 and P = 0.004, respectively). The rs3200401C allele could be a protective factor for AC and SCC development (OR = 0.57; 95% CI = 0.38– 0.85; OR = 0.72; 95% CI = 0.58– 0.90). Moreover, the rs3200401C allele could be a protective factor for cervical cancer stage I development (OR = 0.67; 95% CI = 0.53– 0.86).Conclusion: Our results indicate that rs3200401 in MALAT1 and rs4977574 in ANRIL could play key roles in the CC development.Keywords: cervical cancer, single-nucleotide polymorphisms, long non-coding RNAs, association study