Cumulative Risk Impact of Five Genetic Variants Associated with Papillary Thyroid Carcinoma
Cumulative Risk Impact of Five Genetic Variants Associated with Papillary Thyroid Carcinoma
复制标题
DOI：
10.1089/thy.2013.0102
复制
发表时间：
2013-12-01
期刊：
影响因子：
6.6
通讯作者：
de la Chapelle, Albert
中科院分区：
文献类型：
--
作者：
Liyanarachchi, Sandya;Wojcicka, Anna;de la Chapelle, Albert
背景资料：最近的两项全基因组关联研究（GWAS）确定了与甲状腺乳头状癌（PTC）相关的5个单核苷酸多态性（SNP; rs 965513，rs 944289，rs 966423，rs 2439302和rs 116909374）。每种变异都显示出高度显著但中度至低度的疾病风险。在这里，我们评估了五个SNP的累积风险和预测价值。方法：我们对来自俄亥俄州的747例PTC病例和1047例对照以及来自波兰的1795例PTC病例和2090例对照进行了基因分型。使用未加权和加权方法计算累积遗传风险评分。结果：5个SNPs均与PTC相关。病例组的平均累积风险评分显著高于对照组（p5）。与低分组个体相比，高分组个体对PTC的易感性显著更高，俄亥俄州和波兰的比值比分别为8.7 [95% CI 5.8，13.3]和4.24 [95% CI 3.10，5.84]。当省略滤泡变体PTC和microPTC时，获得了几乎相同的结果。这五个SNPs解释了俄亥俄州队列中11%的甲状腺癌家族风险和波兰队列中6%的甲状腺癌家族风险。结论：随着遗传风险评分的增加，PTC的风险增加。然而，这五种变异的累积效应的预测能力仅中等程度高，并且在检测到更多变异之前，临床使用可能不可行。
Background: Two recent genome-wide association studies (GWASs) identified five single nucleotide polymorphisms (SNPs; rs965513, rs944289, rs966423, rs2439302, and rs116909374) associated with papillary thyroid carcinoma (PTC). Each variant showed highly significant but moderate to low disease risk. Here we assessed the cumulative risk and predictive value of the five SNPs. Methods: We genotyped two cohorts of individuals, 747 PTC cases and 1047 controls from Ohio and 1795 PTC cases and 2090 controls from Poland. Cumulative genetic risk scores were calculated using unweighted and weighted approaches. Results: All five SNPs showed significant association with PTC. The average cumulative risk score in cases was significantly higher than in controls (p5). Individuals in the high group were significantly more susceptible to PTC compared with individuals in the low group with an odds ratio of 8.7 [95% CI 5.8, 13.3] in Ohio and 4.24 [95% CI 3.10, 5.84] in Poland. Almost identical results were obtained when follicular variant PTCs and microPTCs were omitted. These five SNPs explained 11% of the familial risk of thyroid cancer in the Ohio cohort and 6% in the Polish cohort. Conclusion: As the genetic risk score increases, the risk of having PTC increases. However, the predictive power of the cumulative effect of these five variants is only moderately high and clinical use may not be feasible until more variants are detected.