Clinical Trial: Gene Analysis in Studying Susceptibility to Wilms Tumor

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: A Genome-Wide Association Study in Wilms Tumor

Brief Summary: This clinical trial studies gene analysis in studying susceptibility to Wilms tumor. Finding genetic markers for Wilms tumor may help identify patients who are at risk of relapse.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To use a genome-wide association analysis to identify novel genetic variants that confer susceptibility to Wilms tumor.

II. To improve our understanding of the genetic architecture and etiology of Wilms tumor.

III. To facilitate the identification of genetic markers that are associated with an increased risk of developing of Wilms tumor and/or those at risk of aggressive disease, relapse, additional tumors and/or cancer in their offspring.

OUTLINE:

Samples are analyzed for single nucleotide polymorphism (SNP) profiling using real-time polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA).


Sponsor: Children's Oncology Group

Current Primary Outcome:

  • Frequencies between cases and controls at each SNP [ Time Frame: Baseline ]
    Compared using the Cochran Armitage trend test (1-df). The data will be analyzed individually for the UK/US study populations and combined using a Mantel-Haenszel analysis adjusting for study group, and related methods which allow for different effects in each population (for confirmed loci, we will compare effects across populations).
  • Frequency of maternal and paternal allelic transmission for risk alleles [ Time Frame: Baseline ]
    Compared using a chi-squared test.
  • Genetic variation on sub-phenotypes such as age at diagnosis, unilateral or bilateral disease, sex, and ethnicity [ Time Frame: Baseline ]
  • Interactions between genetic variation and treatment success or prognosis [ Time Frame: Baseline ]
  • Interactions between germline genetic variation and tumor phenotypes [ Time Frame: Baseline ]


Original Primary Outcome: Use a genome-wide association analysis to identify novel genetic variants that confer susceptibility to Wilms tumor [ Time Frame: Baseline ]

Genotype 2000 cases using the Illumina Human660W-Quad BeadChip. This will include 1000 UK cases and 1000 US cases. Genotypes will be compared respectively with existing data from 4500 UK controls and 2000 US controls


Current Secondary Outcome:

Original Secondary Outcome:

  • Improve our understanding of the genetic architecture and etiology of Wilms tumor [ Time Frame: Baseline ]
    Apply methods which increase power to find rare associated variants, for example by looking for extended haplotypes in subsets of the cases.
  • Facilitate the identification of genetic markers that are associated with an increased risk of developing of Wilms tumor and/or those at risk of aggressive disease, relapse, additional tumors and/or cancer in their offspring. [ Time Frame: Baseline ]
    Compare genotype frequencies between cases and controls at each SNP using the Cochran Armitage trend test. We will also undertake genotypic tests. The data will be analyzed individually for the UK/US study populations and combined using analysis adjusting for study group, and related methods which allow for different effects in each population.


Information By: Children's Oncology Group

Dates:
Date Received: March 6, 2013
Date Started: October 2009
Date Completion:
Last Updated: August 18, 2016
Last Verified: July 2016