Department of Head and Neck Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Thyroid. 2013 Jan;23(1):38-44. doi: 10.1089/thy.2012.0228.
Papillary thyroid cancer (PTC) is a common malignancy that frequently harbors a high prevalence of somatic mutations in the oncogenic BRAF gene. As a novel prognostic molecular marker, this gene has drawn much attention in recent years for its potential utility in the risk prognosis and management of PTC. However, the contribution of the germline variants in this gene to PTC remains unclear. The study herein was aimed to investigate the potential association between the inherited BRAF variants and PTC based on a case-control study.
We selected four single-nucleotide polymorphisms (SNPs) and took a systematic step to interrogate whether these SNPs of BRAF are associated with PTC risk by genotyping these SNPs from 368 patients with PTC and 564 healthy controls.
In comparison of cases and controls for the four SNPs, no differences were observed in the genotypic and allelic frequencies, nor was there evidence of an association between BRAF SNPs and overall risk of PTC. After stratification, however, we found a significantly increased risk of PTC attributed to the SNP variants rs17161747, rs1042179, and rs3748093 for those with a family history of cancer, for smokers, and for both those of age <45 years and nondrinkers, respectively. Further, in the PTC cases, those carrying the rs3748093 variant seemed to be less susceptible to developing lymph node metastases, but more likely to suffer from PTC at an earlier age (<45 years).
These preliminary results may provide evidence for the involvement of the common genetic variants scattered throughout the BRAF oncogene in the prediction of PTC onset and progression. In the future, enlarging the number of samples and performing functional studies in this gene may help to validate whether the association truly exists.
甲状腺乳头状癌（PTC）是一种常见的恶性肿瘤，其致癌 BRAF 基因常存在高频的体细胞突变。作为一种新的预后分子标志物，该基因近年来因其在 PTC 的风险预后和管理中的潜在应用而备受关注。然而，该基因中的种系变异与 PTC 的关系尚不清楚。本研究旨在通过病例对照研究，探讨 BRAF 种系变异与 PTC 之间的潜在关联。
我们选择了四个单核苷酸多态性（SNP），并通过对 368 例 PTC 患者和 564 例健康对照者的 SNP 进行基因分型，系统地研究了这些 SNP 是否与 PTC 风险相关。
与病例组和对照组相比，四个 SNP 的基因型和等位基因频率均无差异，也没有证据表明 BRAF SNP 与 PTC 的总体风险相关。然而，分层后，我们发现 rs17161747、rs1042179 和 rs3748093 三个 SNP 变异与有癌症家族史、吸烟、年龄<45 岁且不饮酒的患者 PTC 风险显著增加有关。此外，在 PTC 患者中，携带 rs3748093 变异的患者似乎不易发生淋巴结转移，但更可能在较年轻（<45 岁）时患上 PTC。
这些初步结果可能为 BRAF 癌基因中常见的遗传变异在预测 PTC 发病和进展中的作用提供证据。未来，扩大样本量并对该基因进行功能研究，可能有助于验证这种关联是否真实存在。
