title: Zinc transporter genes and urological cancers: integrated analysis suggests a role for ZIP11 in bladder cancer.
abstract: 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.
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.|Center for Clinical and Translational Science, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.|Mayo Graduate School, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.
authors.forename: Lang
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.
authors.forename: Kari G
authors.initials: KG
authors.lastname: Chaffee
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Parker
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.
authors.forename: Hugues
authors.initials: H
authors.lastname: Sicotte
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA. petersen.gloria@mayo.edu.
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Petersen
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D027682:Cation Transport Proteins
keywords: Association; Risk; Single nucleotide polymorphism; Survival; Urological cancers; Zinc transporter genes