Rare variants in BRCA2 and CHEK2 are associated with the risk of urinary tract cancers

Previous studies have shown that two rare variants, rs11571833 in BRCA2 and rs17879961 in CHEK2 were associated with lung cancer. However, the associations between these two variants and urinary tract cancers risk remain largely unexplored. We applied imputation of three genome-wide association studies published in the database of Genotypes and Phenotypes (dbGaP). Unconditional logistic regression analysis and meta-analysis were performed to assess the association between these two variants and the risk of urinary tract cancers. Our results showed that rs11571833[T] had an effect on urinary tract cancers predisposition (OR(meta) = 1.45, P(meta) = 0.013), especially associated with increased the risk of bladder cancer (OR(meta) = 1.60, P(meta) = 0.010). Moreover, rs17879961[C] had a protective effect on the urinary tract cancers (OR(meta) = 0.67, P(meta) = 1.0 × 10(−3)) and was mostly associated with a lower incidence of renal cell carcinoma (OR(meta) = 0.51, P(meta) = 2.0 × 10(−3)). Together, our study indicates that BRCA2 and CHEK2 play an important role in the genetic susceptibility to urinary tract cancers.