RESEARCH ARTICLE Genetic Variants in DNA Double-Strand Break Repair Genes and Risk of Salivary Gland Carcinoma: A Case-Control Study

DNA double strand break (DSB) repair is the primary defense mechanism against ionizing radiation-induced DNA damage. Ionizing radiation is the only established risk factor for sali-vary gland carcinoma (SGC). We hypothesized that genetic variants in DSB repair genes contribute to individual variation in susceptibility to SGC. To test this hypothesis, we con-ducted a case-control study in which we analyzed 415 single nucleotide polymorphisms (SNPs) in 45 DSB repair genes in 352 SGC cases and 598 controls. Multivariate logistic re-gression analysis was performed to calculate odds ratios (ORs) and 95 % confidence inter-vals (CIs). Rs3748522 in RAD52 and rs13180356 in XRCC4 were significantly associated with SGC after Bonferroni adjustment; ORs (95 % CIs) for the variant alleles of these SNPs were 1.71 (1.40-2.09, P=1.70 × 10-7) and 0.58 (0.45-0.74, P=2.00 × 10-5) respectively. The genetic effects were modulated by histological subtype. The association of RAD52-rs3748522 with SGC was strongest for mucoepidermoid carcinoma (OR=2.21, 95 % CI: 1.55-3.15, P=1.25 × 10-5, n=74), and the association of XRCC4-rs13180356 with SGC was strongest for adenoid cystic carcinoma (OR=0.60, 95 % CI: 0.42-0.87, P=6.91 × 10-3