Department of Human Genetics/Pediatric Division of Medical Genetics, Graduate Program in Genetic Counseling, University of Utah School of Medicine, 15 North 2030 East, Salt Lake City, 84112, Utah, USA.
Department of Population Sciences, University of Utah School of Medicine, Huntsman Cancer Institute, Salt Lake City, Utah, USA.
BMC Cancer. 2019 Mar 1;19(1):190. doi: 10.1186/s12885-019-5381-2.
IDH1/2 mutated glioma has been associated with a germline risk variant, the rs55705857 G allele. The Utah Population Database (UPDB), a computerized genealogy of people in Utah, is a unique resource to evaluate cancer risk in related individuals.
One hundred and two individuals with IDH1/2 mutant or 1p/19q co-deleted glioma were genotyped and linked to the UPDB. DNA came from blood (21), tumor tissue (43), or both (38). We determined congruence between somatic and germline samples and estimated the relative risk for developing cancer to first and second-degree relatives of G and A allele carriers at rs55705857.
Somatic (glioma) DNA had 85.7% sensitivity (CI 57.2-98.2%) and 95.8% specificity (CI 78.9-99.89%) for germline rs55705857 G allele. Forty-one patients were linked to pedigrees in the UPDB with at least three generations of data. First-degree relatives of rs55705857 G allele carriers were at significantly increased risk for developing cancer (RR = 1.72, p = 0.045, CI 1.02-2.94), and specifically for oligodendroglioma (RR = 57.61, p = 0.017, CI 2.96-320.98) or prostate cancer (RR = 4.10, p = 0.008, CI 1.62-9.58); relatives of individuals without the G allele were not at increased risk. Second-degree relatives of G allele carriers also had significantly increased risk for developing cancer (RR = 1.50, p = 0.007, CI 1.15-2.01).
Tumor DNA may approximate genotype at the rs55705857 locus. We confirmed this locus confers an increased risk of all cancers and especially of oligodendroglioma. No increased cancer or brain tumor risk is seen in family members of individuals without the high-risk G allele.
IDH1/2 突变型脑肿瘤与种系风险变异 rs55705857G 等位基因有关。犹他州人口数据库 (UPDB) 是犹他州人群的计算机化家谱，是评估相关个体癌症风险的独特资源。
102 名 IDH1/2 突变或 1p/19q 共缺失脑肿瘤患者进行了基因分型，并与 UPDB 相关联。DNA 来自血液 (21)、肿瘤组织 (43) 或两者兼有 (38)。我们确定了体细胞和种系样本之间的一致性，并估计了 rs55705857 处 G 和 A 等位基因携带者的一级和二级亲属患癌症的相对风险。
体细胞 (脑肿瘤) DNA 对 rs55705857G 等位基因的灵敏度为 85.7%(CI57.2-98.2%)，特异性为 95.8%(CI78.9-99.89%)。41 名患者与 UPDB 中的家系相关联，这些家系至少有三代数据。rs55705857G 等位基因携带者的一级亲属患癌症的风险显著增加 (RR=1.72，p=0.045，CI1.02-2.94)，特别是患少突胶质细胞瘤 (RR=57.61，p=0.017，CI2.96-320.98)或前列腺癌 (RR=4.10，p=0.008，CI1.62-9.58)；没有 G 等位基因的个体的亲属没有增加的风险。G 等位基因携带者的二级亲属患癌症的风险也显著增加 (RR=1.50，p=0.007，CI1.15-2.01)。
肿瘤 DNA 可能近似于 rs55705857 位点的基因型。我们证实该基因座增加了所有癌症的风险，特别是少突胶质细胞瘤的风险。在没有高危 G 等位基因的个体的家庭成员中，没有发现癌症或脑肿瘤风险增加。
