端粒酶逆转录酶基因多态性与女性甲状腺乳头状癌的相关性。

Association between hTERT Polymorphisms and Female Papillary Thyroid Carcinoma.

机构信息

The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410000, China.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China.

出版信息

Recent Pat Anticancer Drug Discov. 2019;14(3):268-279. doi: 10.2174/1574892814666190919145453.

DOI:10.2174/1574892814666190919145453

PMID:31538903

Abstract

BACKGROUND

A previous genome-wide association study showed that hTERT rs10069690 and rs2736100 polymorphisms were associated with thyroid cancer risk.

OBJECTIVE

This study further investigated the association between increased risk and clinicopathologic characteristics for Papillary Thyroid Carcinoma (PTC) and hTERT polymorphisms rs10069690 or rs2736100 in a Chinese female population.

METHODS

The hTERT genotypes of 276 PTC patients and 345 healthy subjects were determined with regard to SNPs rs10069690 and rs2736100. The association between these SNPs and the risk of PTC and clinicopathologic characteristics was investigated by logistic regression.

RESULTS

We found a significant difference between PTC and rs10069690 (Odds Ratio (OR) = 1.515; P = 0.005), but not between PTC and rs2736100. When the analysis was limited to females, rs10069690 and rs2736100 were both associated with increased risk for PTC in female individuals (OR = 1.647, P = 0.007; OR = 1.339, P = 0.041, respectively). Further haplotype analysis revealed a stimulative effect of haplotypes TC and CA of TERT rs10069690-rs2736100, which increased risk for PTC in female individuals (OR = 1.579, P = 0.014; OR = 0.726, P = 0.025, respectively). Furthermore, the heterozygote A/C of rs2736100 showed significant difference for age (OR = 0.514, P = 0.047).

CONCLUSION

Our finding suggests that hTERT polymorphisms rs10069690 and rs2736100 are associated with increased risk for PTC in Chinese female population and rs2736100 may be related to age. Consistent with US20170360914 and US20170232075, they are expected to be a potential molecular target for anti-cancer therapy.

摘要

背景

先前的全基因组关联研究表明，端粒酶逆转录酶(rs10069690 和 rs2736100)多态性与甲状腺癌风险相关。

目的

本研究进一步探讨了 hTERT 多态性 rs10069690 或 rs2736100 与中国女性人群中甲状腺乳头状癌(PTC)发生风险及临床病理特征的关系。

方法

采用 SNP rs10069690 和 rs2736100 检测 276 例 PTC 患者和 345 例健康对照者的 hTERT 基因型。采用 logistic 回归分析这些 SNP 与 PTC 发病风险及临床病理特征的关系。

结果

我们发现 PTC 与 rs10069690 之间存在显著差异(比值比(OR)=1.515;P=0.005)，但与 rs2736100 之间无显著差异。当分析仅限于女性时，rs10069690 和 rs2736100 均与女性 PTC 发病风险增加相关(OR=1.647，P=0.007;OR=1.339，P=0.041)。进一步的单体型分析显示 TERT rs10069690-rs2736100 的 TC 和 CA 单体型具有刺激作用，可增加女性 PTC 的发病风险(OR=1.579，P=0.014;OR=0.726，P=0.025)。此外，rs2736100 的杂合子 A/C 对年龄有显著差异(OR=0.514，P=0.047)。