Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008 PR China.
Department of Gynecologic Tumor, Affiliated Cancer Hospital of Central South University, Changsha, Hunan 410013 PR China.
Taiwan J Obstet Gynecol. 2020 Mar;59(2):220-226. doi: 10.1016/j.tjog.2020.01.001.
Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) involves alteration of the structure, function, intracellular localization and/or stability of the phosphorylated protein on serine or threonine residues which relates to inflammation and tumorigenesis. Association between PIN1 promoter polymorphisms and cancer risk were reported in several cancers. We intend to study the relationship between the polymorphism of PIN1 promoter and cervical cancer initiation and development.
We genotyped two common single nucleotide polymorphisms (SNPs) (rs2233678 and rs2233679) in the promoter of the PIN1 gene in healthy controls, patients with CIN or cervical cancer. We used polymerase chain reaction and DNA sequencing methods to analyze these two SNPs in 179 patients and 223 healthy controls. Luciferase activity assay was used to detect PIN1 expression driven by the rs2233679.
The results revealed that the carriers of rs2233679 genotypes CT/TT had a significantly increased risk of cervical cancer in patients with CIN compared with genotype CC (odds ration [OR] = 2.924, 95% confidence interval [CI] = 1.093-7.819, P = 0.033). Luciferase activity assay results revealed that PIN1 expression driven by the rs2233679 genotype TT was higher than the genotype CC (P < 0.05). On the other hand, no significant correlation between the healthy controls and patients was found for PIN1 rs2233678 which showed that rs2233678 genotypes CG/GG is 95% in healthy controls and 100% in patients.
PIN1 rs2233679 genotype CT/TT may be a risk factor of early cervical cancer compared with genotype CC in Hunan populations. Our findings suggest that PIN1 rs2233679 genotype CT/TT might involve in the progression of the precancerous stage developing to early cancer by enhancing PIN1 expression.
肽基脯氨酰顺/反异构酶 NIMA 相互作用 1（PIN1）涉及磷酸化丝氨酸或苏氨酸残基上蛋白质的结构、功能、细胞内定位和/或稳定性的改变，与炎症和肿瘤发生有关。已经在几种癌症中报道了 PIN1 启动子多态性与癌症风险之间的关联。我们旨在研究 PIN1 启动子多态性与宫颈癌发生和发展的关系。
我们对健康对照组、CIN 患者或宫颈癌患者的 PIN1 基因启动子中的两个常见单核苷酸多态性（SNP）（rs2233678 和 rs2233679）进行了基因分型。我们使用聚合酶链反应和 DNA 测序方法分析了这两个 SNP 在 179 名患者和 223 名健康对照者中的情况。荧光素酶活性测定用于检测 rs2233679 驱动的 PIN1 表达。
结果表明，与 CC 基因型相比，CIN 患者中 rs2233679 基因型 CT/TT 的携带者患宫颈癌的风险显著增加（比值比 [OR] = 2.924，95%置信区间 [CI] = 1.093-7.819，P = 0.033）。荧光素酶活性测定结果表明，rs2233679 基因型 TT 驱动的 PIN1 表达高于 CC 基因型（P < 0.05）。另一方面，在健康对照组和患者组之间，PIN1 rs2233678 没有发现显著相关性，表明 rs2233678 基因型 CG/GG 在健康对照组中占 95%，在患者中占 100%。
与 CC 基因型相比，湖南人群中 rs2233679 基因型 CT/TT 可能是宫颈癌早期的危险因素。我们的研究结果表明，PIN1 rs2233679 基因型 CT/TT 可能通过增强 PIN1 表达而参与癌前病变进展为早期癌症的过程。
