Jiang Rui, Zhao Chunming, Xu Hao, Zhao Miaoqing, Sun Xiaogang, Wang Xinyu, Song Wei
Department of Oncology, Provincial Hospital Affiliated to Shandong University, Jinan, China.
Department of Ophthalmology, Provincial Hospital Affiliated to Shandong University, Jinan, China.
Clin Endocrinol (Oxf). 2016 Mar;84(3):431-7. doi: 10.1111/cen.12804. Epub 2015 Jun 1.
Papillary thyroid carcinoma (PTC), which accounts for 80% of all thyroid cancers, has an increasing incidence over these years. Single nucleotide polymorphisms (SNPs) of BRAF were considered to be one of well-established risk factors leading to development of PTC. The aim of this study was to investigate whether the common mutations of BRAF could elevate significantly the risk of PTC in a Chinese population.
Four SNPs (rs11762469, rs17623204, rs1267636 and rs3748093) of BRAF were selected through our filter by Haploview 4.2 software with HapMap databases. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to genotype the four SNPs in blood samples of 618 subjects (206 patients with PTC and 412 healthy controls). The correlation between BRAF polymorphisms and PTC risk was assessed using student t-test and chi-square test.
The results showed that mutation in rs3748093 was significantly associated with an increased risk of PTC in allele model (A allele vs. T allele, OR = 1·68, 95% CI = 1·16-2·43, P = 0·006), dominant model (TA + AA vs TT, OR = 1·64, 95% CI = 1·08-2·48, P = 0·019) and homozygote model (AA vs. TT, OR = 2·94, 95% CI = 1·00-8·61, P = 0·040). However, the other three SNPs (rs11762469, rs17623204 and rs1267636) were shown to have no association with the risk of PTC.
Our results indicated that polymorphism of rs3748093*A was significantly correlated with an increased risk of PTC in a Chinese population. Further investigation on the aetiological mechanism of PTC is needed to validate our results.
甲状腺乳头状癌（PTC）占所有甲状腺癌的80%，近年来其发病率呈上升趋势。BRAF基因的单核苷酸多态性（SNP）被认为是导致PTC发生的公认危险因素之一。本研究旨在探讨BRAF常见突变是否会显著增加中国人群患PTC的风险。
通过Haploview 4.2软件和HapMap数据库筛选出BRAF基因的4个SNP（rs11762469、rs17623204、rs1267636和rs3748093）。我们采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对618名受试者（206例PTC患者和412名健康对照）的血样中的这4个SNP进行基因分型。使用学生t检验和卡方检验评估BRAF基因多态性与PTC风险之间的相关性。
结果显示，rs3748093突变在等位基因模型（A等位基因与T等位基因，OR = 1.68，95%CI = 1.16 - 2.43，P = 0.006）、显性模型（TA + AA与TT，OR = 1.64，95%CI = 1.08 - 2.48，P = 0.019）和纯合子模型（AA与TT，OR = 2.94，95%CI = 1.00 - 8.61，P = 0.040）中与PTC风险增加显著相关。然而，其他3个SNP（rs11762469、rs17623204和rs1267636）与PTC风险无关。
我们的结果表明，rs3748093*A多态性与中国人群PTC风险增加显著相关。需要对PTC的病因机制进行进一步研究以验证我们的结果。
