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维生素D受体基因FokI多态性作为甲状腺乳头状癌的不良预后因素

VDR gene FokI polymorphism as a poor prognostic factor for papillary thyroid cancer.

作者信息

Beysel Selvihan, Eyerci Nilnur, Pinarli Ferda Alparslan, Apaydin Mahmut, Kizilgul Muhammed, Caliskan Mustafa, Ozcelik Ozgur, Kan Seyfullah, Cakal Erman

机构信息

1 Department of Endocrinology and Metabolism, Ankara Diskapi Yildirim Beyazit Teaching and Research Hospital, Ankara, Turkey.

2 Department of Medical Biology, Başkent University, Ankara, Turkey.

出版信息

Tumour Biol. 2018 Nov;40(11):1010428318811766. doi: 10.1177/1010428318811766.

Abstract

This is the first study to investigate the effect of vitamin D receptor ( VDR) gene single-nucleotide polymorphisms on the clinicopathologic features of papillary thyroid cancer in Turkey. A total of 165 patients with papillary thyroid cancer and 172 controls were included in this case-control study. VDR gene single-nucleotide polymorphisms FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) were evaluated using reverse-transcription polymerase chain reaction. VDR gene polymorphisms BsmI, ApaI, and TaqI did not differ between the papillary thyroid cancer group and control group (p > 0.05, each). BsmI, ApaI, and TaqI were not associated with papillary thyroid cancer risk. The VDR gene FokI CT/TT genotype was associated with an increased papillary thyroid cancer risk (CT vs CC: odds ratio = 1.71, 95% confidence interval = 1.15-2.76, p = 0.028; TT vs CC: odds ratio = 2.44, 95% confidence interval = 1.29-4.62, p = 0.005; CT/TT vs CC: odds ratio = 1.88, 95% confidence interval = 1.20-2.96, p = 0.006; CT/CC vs TT: odds ratio = 1.80, 95% confidence interval = 1.05-3.20, p = 0.041). VDR gene polymorphisms were not in linkage disequilibrium. The FokI TT genotype was associated with having T3 and T4, stage III/IV, extra-thyroidal invasion. The FokI CT/TT or TT genotype was associated with developing N1 status, multifocality, tumor size ≥10 mm, and treatment with radioiodine therapy. Persistence/recurrence did not differ between the FokI genotypes. Carriers of the FokI T allele were at an increased risk of more advanced tumor-node-metastasis stage, greater tumor size, multifocality, and extra-thyroidal invasion of papillary thyroid cancer compared with the CC genotype. VDR gene FokI T allele and TT genotype correlated with aggressiveness of papillary thyroid cancer; thus, FokI could be useful as a poor prognostic factor to assess the high risk of papillary thyroid cancer.

摘要

这是第一项研究维生素D受体(VDR)基因单核苷酸多态性对土耳其乳头状甲状腺癌临床病理特征影响的研究。本病例对照研究共纳入165例乳头状甲状腺癌患者和172例对照。使用逆转录聚合酶链反应评估VDR基因单核苷酸多态性FokI(rs2228570)、BsmI(rs1544410)、ApaI(rs7975232)和TaqI(rs731236)。乳头状甲状腺癌组和对照组之间的VDR基因多态性BsmI、ApaI和TaqI无差异(各p>0.05)。BsmI、ApaI和TaqI与乳头状甲状腺癌风险无关。VDR基因FokI CT/TT基因型与乳头状甲状腺癌风险增加相关(CT与CC相比:比值比=1.71,95%置信区间=1.15 - 2.76,p = 0.028;TT与CC相比:比值比=2.44,95%置信区间=1.29 - 4.62,p = 0.005;CT/TT与CC相比:比值比=1.88,95%置信区间=1.20 - 2.96,p = 0.006;CT/CC与TT相比:比值比=1.80,95%置信区间=1.05 - 3.20,p = 0.041)。VDR基因多态性不存在连锁不平衡。FokI TT基因型与出现T3和T4、III/IV期、甲状腺外侵犯相关。FokI CT/TT或TT基因型与出现N1状态、多灶性、肿瘤大小≥10 mm以及接受放射性碘治疗相关。FokI基因型之间的持续存在/复发无差异。与CC基因型相比,FokI T等位基因携带者发生更晚期肿瘤-淋巴结-转移分期、更大肿瘤大小、多灶性和乳头状甲状腺癌甲状腺外侵犯的风险增加。VDR基因FokI T等位基因和TT基因型与乳头状甲状腺癌的侵袭性相关;因此,FokI可作为评估乳头状甲状腺癌高风险的不良预后因素。

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