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Zinc transporter genes and urological cancers: integrated analysis suggests a role for ZIP11 in bladder cancer

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Tumor Biology

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.

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Acknowledgments

The authors thank the dataset contributors and participants in the prostate, bladder, and renal cell carcinoma case-control studies. We also thank dbGaP for providing access to the datasets (dbGaP Study Accession: phs000207.v1.p1, phs000346.v1.p1, and phs000351.v1.p1). This publication was made possible by CTSA Grant Number UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH) as well as Mayo Graduate School fellowship. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH.

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Authors and Affiliations

  1. Department of Health Sciences Research, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA

    Lang Wu, Kari G. Chaffee, Hugues Sicotte & Gloria M. Petersen

  2. Center for Clinical and Translational Science, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA

    Lang Wu

  3. Mayo Graduate School, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA

    Lang Wu

  4. Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA

    Alexander S. Parker

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  1. Lang Wu
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Correspondence to Gloria M. Petersen.

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Wu, L., Chaffee, K.G., Parker, A.S. et al. Zinc transporter genes and urological cancers: integrated analysis suggests a role for ZIP11 in bladder cancer. Tumor Biol. 36, 7431–7437 (2015). https://doi.org/10.1007/s13277-015-3459-2

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  • DOI: https://doi.org/10.1007/s13277-015-3459-2

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