Marcotte Erin L, Pankratz Nathan, Amatruda James F, Frazier A Lindsay, Krailo Mark, Davies Stella, Starr Jacqueline R, Lau Ching C, Roesler Michelle, Langer Erica, Hallstrom Caroline, Hooten Anthony J, Poynter Jenny N
Division of Epidemiology & Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.
Genes Chromosomes Cancer. 2017 Jul;56(7):548-558. doi: 10.1002/gcc.22457. Epub 2017 Apr 4.
Germ cell tumors (GCT) are a rare form of childhood cancer that originate from the primordial germ cell. Recent genome-wide association studies (GWAS) have identified susceptibility alleles for adult testicular GCT (TGCT). We test whether these SNPs are associated with GCT in pediatric and adolescent populations. This case-parent triad study includes individuals with GCT diagnosed between ages 0 and 19. We evaluated 26 SNPs from GWAS of adult TGCT and estimated main effects for pediatric GCT within complete trios (N = 366) using the transmission disequilibrium test. We used Estimation of Maternal, Imprinting and interaction effects using Multinomial modelling to evaluate maternal effects in non-Hispanic white trios and dyads (N = 244). We accounted for multiple comparisons using a Bonferroni correction. A variant in SPRY4 (rs4624820) was associated with reduced risk of GCT (OR [95% CI]: 0.70 [0.57, 0.86]). A variant in BAK1 (rs210138) was positively associated with GCT (OR [95% CI]: 1.70 [1.32, 2.18]), with a strong estimated effect for testis tumors (OR [95% CI]: 3.31 [1.89, 5.79]). Finally, a SNP in GAB2 (rs948662) was associated with increased risk for GCT (OR [95% CI]: 1.56 [1.20, 2.03]). Nominal associations (P < 0.05) were noted for eight additional loci. A maternal effect was observed for KITLG SNP rs4474514 (OR [95% CI]: 1.66 [1.21, 2.28]) and a paternal parent-of-origin effect was observed for rs7221274 (P = 0.00007), near TEX14, RAD51C, and PPM1E. We observed associations between SNPs in SPRY4, BAK1, and GAB2 and GCTs. This analysis suggests there may be common genetic risk factors for GCT in all age groups.
生殖细胞肿瘤（GCT）是一种罕见的儿童癌症，起源于原始生殖细胞。最近的全基因组关联研究（GWAS）已经确定了成人睾丸生殖细胞肿瘤（TGCT）的易感等位基因。我们测试这些单核苷酸多态性（SNP）是否与儿童和青少年人群中的GCT相关。这项病例-父母三联体研究纳入了0至19岁被诊断为GCT的个体。我们评估了来自成人TGCT的GWAS的26个SNP，并使用传递不平衡检验估计了完整三联体（N = 366）中儿童GCT的主要效应。我们使用多项模型估计母体、印记和相互作用效应，以评估非西班牙裔白人三联体和二元组（N = 244）中的母体效应。我们使用Bonferroni校正来考虑多重比较。SPRY4中的一个变体（rs4624820）与GCT风险降低相关（比值比[95%可信区间]：0.70[0.57，0.86]）。BAK1中的一个变体（rs210138）与GCT呈正相关（比值比[95%可信区间]：1.70[1.32，2.18]），对睾丸肿瘤的估计效应较强（比值比[95%可信区间]：3.31[1.89，5.79]）。最后，GAB2中的一个SNP（rs948662）与GCT风险增加相关（比值比[95%可信区间]：1.56[1.20，2.03]）。另外八个位点存在名义上的关联（P < 0.05）。在KITLG SNP rs4474514中观察到母体效应（比值比[95%可信区间]：1.66[1.21，2.28]），在rs7221274中观察到父系亲本来源效应（P = 0.00007），该位点靠近TEX14、RAD51C和PPM1E。我们观察到SPRY4、BAK1和GAB2中的SNP与GCT之间存在关联。该分析表明，所有年龄组的GCT可能存在共同的遗传风险因素。
