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

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)7431-7437
Number of pages7
JournalTumor Biology
Volume36
Issue number10
DOIs
StatePublished - Apr 23 2015

Fingerprint

Urologic Neoplasms
Urinary Bladder Neoplasms
Odds Ratio
Confidence Intervals
Atlases
Genes
Neoplasms
Prostatic Neoplasms
Logistic Models
Genome
Encyclopedias
Survival
Kidney Neoplasms
Genome-Wide Association Study
Genetic Association Studies
Missense Mutation
Renal Cell Carcinoma
Genotype
zinc-binding protein
DNA

Keywords

  • Association
  • Risk
  • Single nucleotide polymorphism
  • Survival
  • Urological cancers
  • Zinc transporter genes

ASJC Scopus subject areas

  • Cancer Research

Cite this

Zinc transporter genes and urological cancers : integrated analysis suggests a role for ZIP11 in bladder cancer. / Wu, Lang; Chaffee, Kari G.; Parker, Alexander; Sicotte, Hugues; Petersen, Gloria M.

In: Tumor Biology, Vol. 36, No. 10, 23.04.2015, p. 7431-7437.

Research output: Contribution to journalArticle

@article{370a14bfe8604a909a3882d7d6aa9ea4,
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.",
keywords = "Association, Risk, Single nucleotide polymorphism, Survival, Urological cancers, Zinc transporter genes",
author = "Lang Wu and Chaffee, {Kari G.} and Alexander Parker and Hugues Sicotte and Petersen, {Gloria M}",
year = "2015",
month = "4",
day = "23",
doi = "10.1007/s13277-015-3459-2",
language = "English (US)",
volume = "36",
pages = "7431--7437",
journal = "Tumor Biology",
issn = "1010-4283",
publisher = "Springer Netherlands",
number = "10",

}

TY - JOUR

T1 - Zinc transporter genes and urological cancers

T2 - integrated analysis suggests a role for ZIP11 in bladder cancer

AU - Wu, Lang

AU - Chaffee, Kari G.

AU - Parker, Alexander

AU - Sicotte, Hugues

AU - Petersen, Gloria M

PY - 2015/4/23

Y1 - 2015/4/23

N2 - 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.

AB - 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.

KW - Association

KW - Risk

KW - Single nucleotide polymorphism

KW - Survival

KW - Urological cancers

KW - Zinc transporter genes

UR - http://www.scopus.com/inward/record.url?scp=84944274753&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84944274753&partnerID=8YFLogxK

U2 - 10.1007/s13277-015-3459-2

DO - 10.1007/s13277-015-3459-2

M3 - Article

C2 - 25900876

AN - SCOPUS:84944274753

VL - 36

SP - 7431

EP - 7437

JO - Tumor Biology

JF - Tumor Biology

SN - 1010-4283

IS - 10

ER -