Owens Patrick W, McVeigh Terri Patricia, Miller Nicola, Guerin Carole, Sebag Frederic, Quill Denis, Bell Marcia, Kerin Michael J, Lowery Aoife J
Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, National University of Ireland, Galway, Ireland.
Cancer Genetics Unit Royal Marsden NHS Foundation Trust, London, England.
Endocr Oncol. 2021 May 19;1(1):1-8. doi: 10.1530/EO-21-0003. eCollection 2021 Jan.
is an intronless gene on chromosome 9 which plays a significant role in thyroid morphogenesis. Mutations in are associated with thyroid phenotypes including congenital hypothyroidism, thyroid dysgenesis and thyroid cancer. This study aims to investigate the frequency and impact of a SNP (rs965513, G>A) at 9q22.23 in a Western European cohort of patients with differentiated thyroid cancer(DTC), compared to controls.
This is a candidate gene case control study.
277 patients with histologically confirmed DTC were recruited from tertiary referral centres in Ireland and France. 309 cancer-free controls were recruited from the community. DNA was extracted from buccal swabs or whole blood of control subjects and patients with DTC. Allelic and genotypic frequencies among patients were compared with controls, to assess the risk for disease conferred by homozygous and heterozygous carriers compared to WT genotypes. Genotyping was performed using Taqman-based PCR.
277 patients with confirmed DTC and 309 non-cancer controls were genotyped for the variant (rs965513). The frequency of the minor allele among cases was 0.45 compared to 0.34 among controls. The genotypic odds ratio for heterozygotes was 1.66 (CI 1.16-2.39, =0.00555), increasing to 2.93 (CI 1.70-5.05, =0.00007) for rare homozygotes. All subjects were in Hardy-Weinberg equilibrium (±, =0.09, =0.07 respectively).
This polymorphism is a low penetrance variant associated with DTC susceptibility in this cohort. The minor allele was identified among patients with thyroid cancer significantly more frequently than controls. An allele dosage effect was observed, with rare homozygous genotypes conferring greater risk than heterozygotes.
是位于9号染色体上的一个无内含子基因，在甲状腺形态发生中起重要作用。该基因的突变与包括先天性甲状腺功能减退、甲状腺发育不全和甲状腺癌在内的甲状腺表型相关。本研究旨在调查与对照组相比，西欧分化型甲状腺癌（DTC）患者队列中9q22.23处单核苷酸多态性（SNP，rs965513，G>A）的频率及其影响。
这是一项候选基因病例对照研究。
从爱尔兰和法国的三级转诊中心招募了277例经组织学确诊的DTC患者。从社区招募了309名无癌对照。从对照受试者和DTC患者的颊拭子或全血中提取DNA。将患者中的等位基因和基因型频率与对照进行比较，以评估纯合子和杂合子携带者与野生型基因型相比的疾病风险。使用基于Taqman的PCR进行基因分型。
对277例确诊的DTC患者和309例非癌对照进行了该变体（rs965513）的基因分型。病例中次要等位基因的频率为0.45，而对照中为0.34。杂合子的基因型优势比为1.66（CI 1.16 - 2.39，P = 0.00555），罕见纯合子的优势比增至2.93（CI 1.70 - 5.05，P = 0.00007）。所有受试者均处于哈迪 - 温伯格平衡（P分别为0.09和0.07）。
这种多态性是该队列中与DTC易感性相关的低外显率变体。在甲状腺癌患者中发现次要等位基因的频率明显高于对照。观察到等位基因剂量效应，罕见的纯合子基因型比杂合子具有更高的风险。
