EPID-11. THE CONTRIBUTION OF THE rs55705857 G ALLELE TO FAMILIAL CANCER RISK USING THE UTAH POPULATION DATABASE Free

IDH1/2 mutated glioma is associated with the presence of a germline risk variant, the rs55705857 G allele. The Utah Population Database (UPDB) is a unique prospective resource for evaluating cancer risk in related individuals. We aimed to determine the risk of glioma and other cancers in relatives of patients with IDH1/2 mutant glioma based on rs55705857 alleles.

Patients with IDH1/2 mutant or 1p/19q co-deleted glioma were identified. Samples of either blood or tumor were obtained from the Huntsman Cancer Institute Cancer Clinical Research Database. For those people with DNA available from both blood and tumor, we compared the genotyping results to determine if tumor accurately represents rs55705857 genotype. One hundred and two individuals were genotyped and linked to the UPDB. We determined congruence between somatic and germline samples and estimated the relative risk (RR) to first and second-degree relatives of G allele carriers to develop cancers associated with IDH1/2 mutations.

Somatic DNA had 85.7 % Sensitivity (CI 57.2%-98.2%) and 95.8 % Specificity (CI 78.9%-99.89%) for the rs55705857 G allele. Forty-one patients linked to three-generation pedigrees in the UPDB. First-degree relatives of rs55705857 G allele carrier patients are at significantly increased risks for developing any cancer (RR = 1.72, p=0.045, CI 1.02-2.94), and specifically 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), but relatives of people without the rs55705857 G allele are not at increased risk. Second-degree relatives of G allele carriers also had an overall increased risk for developing cancer (RR = 1.50, p=0.007, CI 1.15-2.01).

Tumor DNA accurately reflects rs55705857 genotype. The G allele at this locus confers an increased risk of all cancers and of oligodendroglioma in relatives. No increased cancer or brain tumor risk was seen in family members of people without the G allele SNP rs55705857.