Vinothkumar Vilvanathan, Arun Kanagaraj, Arunkumar Ganesan, Revathidevi Sundaramoorthy, Ramani Rajendren, Bhaskar Lakkakula V K S, Murugan Avaniyapuram Kannan, Munirajan Arasambattu Kannan
Department of Genetics, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, Tamil Nadu 600113, India.
Institute of Social Obstetrics and Government Kasturba Gandhi Hospital for Women and Children, Chennai, Tamil Nadu 600005, India.
Mol Clin Oncol. 2020 May;12(5):485-494. doi: 10.3892/mco.2020.2003. Epub 2020 Feb 26.
A single nucleotide polymorphism (SNP) rs2853669 (A>G) in the telomerase reverse transcriptase (TERT) promoter has recently been reported in chr5:1,295,349 T>C (T349C), and was shown to be associated with increased cancer risk and poor survival in a specific population. However, at present, the role of this particular SNP with TERT promoter driver mutations and its genetic association with human papilloma virus (HPV) in patients with cervical cancer has not been determined. In the present study, the genetic association of the functional SNP rs2853669 in the presence/absence of TERT promoter hotspot mutations and HPV in patients with cervical cancer of South Indian origin was evaluated. To understand and compare the frequency of the variant allele and its risk association in different cancer types of various populations, the SNP was genotyped in 257 cervical cancer samples and 295 controls, and its associations with TERT promoter hotspot mutations and HPV were analyzed. Furthermore, an extensive search of previously published articles in PubMed, Embase and Web of Science was conducted; a meta-analysis was carried out to elucidate the association of the SNP with different cancer types in global populations. The SNP analysis showed significantly high frequency (41%) of homozygous variant allele rs2853669 (GG) in patients with cervical cancer compared with control samples [Recessive allele model odds ratio (OR)=1.71; 95% CI=1.20-2.43; P=0.003]. No significant interaction was observed between the TERT SNP rs2853669 and HPV status as well as other hotspot TERT promoter (C228T and C250T) mutations determined in our previous study. In addition, the overall meta-analysis revealed a significant association of the SNP rs2853669 with other cancer types in different ethnic populations (OR=1.09; 95% CI=1.03-1.16; P=0.004). The present results suggested that the TERT SNP rs2853669 could play an important role in the risk of cervical cancer in a South Indian population.
端粒酶逆转录酶（TERT）启动子中的单核苷酸多态性（SNP）rs2853669（A>G）最近在5号染色体：1,295,349处被报道为T>C（T349C），并且在特定人群中显示与癌症风险增加和生存率低相关。然而，目前，该特定SNP与TERT启动子驱动突变的作用及其与宫颈癌患者人乳头瘤病毒（HPV）的遗传关联尚未确定。在本研究中，评估了南印度裔宫颈癌患者中功能性SNP rs2853669在存在/不存在TERT启动子热点突变和HPV情况下的遗传关联。为了了解和比较不同人群不同癌症类型中变异等位基因的频率及其风险关联，对257例宫颈癌样本和295例对照进行了该SNP的基因分型，并分析了其与TERT启动子热点突变和HPV的关联。此外，对PubMed、Embase和Web of Science中先前发表的文章进行了广泛检索；进行了荟萃分析以阐明该SNP与全球人群不同癌症类型的关联。SNP分析显示，与对照样本相比，宫颈癌患者中纯合变异等位基因rs2853669（GG）的频率显著较高[隐性等位基因模型优势比（OR）=1.71；95%置信区间（CI）=1.20-2.43；P=0.003]。在我们先前研究中确定的TERT SNP rs2853669与HPV状态以及其他热点TERT启动子（C228T和C250T）突变之间未观察到显著相互作用。此外，总体荟萃分析显示SNP rs2853669与不同种族人群的其他癌症类型存在显著关联（OR=1.09；95%CI=1.03-1.16；P=0.004）。目前的结果表明，TERT SNP rs2853669可能在南印度人群宫颈癌风险中起重要作用。
