Division of Molecular Genetics and Biochemistry, National Institute of Cancer Prevention and Research (ICMR), Noida, Uttar Pradesh, India.
Division of Preventive Oncology, National Institute of Cancer Prevention and Research (Formerly Institute of Cytology and Preventive Oncology (ICPO) (ICMR), I-7, Sector-39, Noida, Gautam Buddha Nagar, Uttar Pradesh 201301, India.
Biosci Rep. 2019 Apr 16;39(4). doi: 10.1042/BSR20180723. Print 2019 Apr 30.
Cervical cancer is the second major female cancer in India and constitutes one-fourth of the world's burden. Human Papilloma Virus (HPV) infection is an essential but insufficient cause for cervical cancer. Genetic variants in microRNAs (miRNAs/miRs) play an important role in the susceptibility of various types of cancers. To evaluate the association of Single Nucleotide Polymorphisms (SNPs) in miR-146a (rs2910164), miR-196a2 (rs11614913), and miR-499 (rs3746444), with cervical cancer susceptibility in Indian population. Three hundred samples were genotyped by Polymerase chain reaction (PCR)-Restriction fragment length polymorphism (RFLP). Both patients and controls were also screened for the presence of HPV DNA. In this case-control study, 125 (83.3%) cervical cancer cases were found to be infected with HPV DNA. The frequency of miR-146a C allele was higher in controls than in cases [odds ratio (OR) (95% confidence interval (CI)) = 0.81 (0.57-1.14), -value = 0.258]. miR-196a2 T allele was found to be associated with the decreased risk of cervical cancer [OR (95% CI) = 0.36 (0.26-0.50), -value<0.0001]. Approximately 1.22-fold increased risk has been observed in individuals carrying miR-499 TT genotypes [OR (95% CI) = 1.22 (0.63-2.36), -value = 0.617]. Interaction studies for miR-196a2/miR-499 loci showed that women carrying TT/CC and TT/CT genotypes were less likely to develop cervical cancer than CC/CC combination [<0.05]. Likewise, miR-146a/miR-196a2 genotypic combinations (CC/TT, CG/TT, GG/TT) followed the similar trend [<0.05], exhibited the protective effect against cervical cancer with reference to CC/CC group. Combined genotypes of miR-146a/miR-499 [CC/CT, CG/CC, CG/CT, CG/TT, GG/CC, GG/CT, GG/TT] demonstrated a non-significant trend toward higher cervical cancer risk [OR > 1.00, >0.05]. Polymorphisms in miR-146a, miR-196a2, and miR-499 individually or collectively have the prospective to emerge as biomarkers for cervical cancer.
宫颈癌是印度第二大女性癌症，占全球负担的四分之一。人乳头瘤病毒（HPV）感染是宫颈癌的一个重要但不充分的病因。微小 RNA（miRNA/miRs）中的基因变异在各种类型癌症的易感性中发挥着重要作用。评估单核苷酸多态性（SNP）在 miR-146a（rs2910164）、miR-196a2（rs11614913）和 miR-499（rs3746444）与印度人群宫颈癌易感性中的相关性。通过聚合酶链反应（PCR）-限制性片段长度多态性（RFLP）对 300 个样本进行基因分型。患者和对照组均筛查 HPV DNA 的存在情况。在这项病例对照研究中，发现 125 例（83.3%）宫颈癌病例感染了 HPV DNA。miR-146a C 等位基因在对照组中的频率高于病例组[比值比（OR）（95%置信区间（CI））= 0.81（0.57-1.14），-值= 0.258]。miR-196a2 T 等位基因与宫颈癌风险降低相关[OR（95%CI）= 0.36（0.26-0.50），-值<0.0001]。携带 miR-499 TT 基因型的个体患宫颈癌的风险增加了约 1.22 倍[OR（95%CI）= 1.22（0.63-2.36），-值= 0.617]。miR-196a2/miR-499 基因座的相互作用研究表明，携带 TT/CC 和 TT/CT 基因型的女性比 CC/CC 组合发生宫颈癌的可能性更小[<0.05]。同样，miR-146a/miR-196a2 基因型组合（CC/TT、CG/TT、GG/TT）也呈现出类似的趋势[<0.05]，与 CC/CC 组相比，对宫颈癌具有保护作用。miR-146a/miR-499 的组合基因型[CC/CT、CG/CC、CG/CT、CG/TT、GG/CC、GG/CT、GG/TT]显示出宫颈癌风险升高的非显著趋势[OR>1.00，>0.05]。miR-146a、miR-196a2 和 miR-499 的单独或组合多态性有可能成为宫颈癌的生物标志物。
