Although
zinc transporters were shown to play roles in the development of prostate, bladder, and
renal cancer, no study has evaluated the genetic variants in
zinc transporter genes with risk of
urological cancers. A candidate gene association study using genome-wide association study (GWAS) datasets was conducted for variants in 24
zinc transporter genes. Genotypes were analyzed using logistic regression models adjusted for covariates. The function of identified variants was assessed by using the Encyclopedia of
DNA Elements (ENCODE). We further evaluated
tumors for somatic change of the implicated gene(s) and the associations between identified variants and patient survival from data in The
Cancer Genome Atlas (TCGA). A ZIP11 variant, rs8081059, was significantly associated with increased risk of
renal cell carcinoma (odds ratios (OR) = 1.28, 95 % confidence intervals (CI) (1.13-1.45), p = 0.049). No
zinc transporter variants were associated with
prostate cancer risk. Four variants within ZIP11 were significantly associated with
bladder cancer risk: rs11871756 (OR = 1.43, 95 % CI (1.24-1.63), p = 0.0002), rs11077654 (OR = 0.76, 95 % CI (0.68-0.85), p = 0.001), rs9913017 (OR = 0.76, 95 % CI (0.68-0.85), p = 0.002), and rs4969054 (OR = 0.78, 95 % CI (0.69-0.88), p = 0.02); the three protective variants were co-located and highly correlated. These variants were located within predicted transcribed or enhancer regions. Among the 253
bladder cancer patients in TCGA, two had
tumors that contained deleterious missense mutations in ZIP11. Moreover, rs11077654 was significantly associated with survival of
bladder cancer patients (p = 0.046). In conclusion,
zinc transporter gene, ZIP11, may play an important role in
bladder cancer. Further studies of the gene are warranted.