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Study Description

This research builds upon an extensive resource of melanoma cases and hospital based controls collected over several years at the U.T. M.D. Anderson Cancer Center. The goal of this research is to identify novel susceptibility and outcome-related genes for melanoma using a systematic genome-wide association-based approach. Our goal is to conduct high-density SNP association and outcome studies. This dbGaP study contains samples from 2000 European ancestry cases and 1000 European ancestry controls using the Illumina OMNI1-Quad SNP chip. As a part of an ongoing R01 project, we have epidemiological data together with candidate gene results for 1000 of the melanoma cases and the controls. With regard to the outcome aspect of our design, as part of our melanoma Specialized Program of Research Excellence (SPORE) grant, our MelCore database contains comprehensive, prospectively maintained clinical information from all melanoma patients included in the study cohort, including primary tumor histopathology and staging information, standard and investigational blood tumor markers, details of surgical and systemic therapies, and extensive follow-up information, including time to relapse or recurrence, pattern of recurrence and survival duration. Finally, we intend to collaborate with the GenoMEL collaboration so we can jointly evaluate each other's findings. The goal of our analysis will be to identify novel genetic factors predisposing the development of melanoma, as well as genetic factors controlling melanoma stage at presentation, recurrence and progression.

This study is part of the Gene Environment Association Studies initiative (GENEVA, funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to melanoma through large-scale genome-wide association studies of 2000 European ancestry cases and 1000 European ancestry controls. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.

  • Study Types: Case-Control, Case Set
  • dbGaP estimated ancestry components using GRAF-pop
  • Number of study subjects that have individual level data available through Authorized Access: 3115

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

In the course of routine data cleaning and data analyses, investigators may incidentally identify genetic abnormalities that might influence the clinical care of an individual. These statements and recommendations have been developed to help investigators when they are informed of any such incidental findings.

  1. GENEVA Statement on Incidental Findings
  2. GENEVA Aneuploidy Reference Table
  3. GENEVA Pharmacogenetic Variants Reference Table

Study Inclusion/Exclusion Criteria

Inclusion: Cases of malignant melanoma seen at M.D. Anderson Cancer Center since 1994. For the case-control study, which began in 1994, only newly diagnosed cases were eligible. Since 2003 all cases referred to either surgical or medical oncology with a diagnosis of malignant melanoma are eligible. Cases had to consent to give blood and be self-described as European ancestry. Controls are European ancestry without a history of prior cancers (other than skin cancer) who were friends or spouses of cases seen at M.D. Anderson Cancer in clinics other than those from whom the cases were referred.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Genotyping Illumina HumanOmni1-Quad_v1-0_B 1051295 1049033
Study History

We are proposing to include all cases from M.D. Anderson Cancer Center who have documented invasive melanomas and available DNA. Tables 1 and 2 provide demographic data on cases seen at M.D. Anderson Cancer Center for whom the SPORE or Dr. Wei's grant have collected both DNA samples and data. There is currently a total of 2159 melanoma cancer cases with DNA available using samples from both Dr. Wei's and the melanoma SPORE and both projects are continuing to accrue subjects. The mean and median age at diagnosis for cases in the combined melamoma R01/SPORE was 50.9, which is about 6 years younger than the mean age of 57 reported by SEER (Lachiewicz et al., 2008). Among the R01/SPORE patients, the median primary Breslow tumor thickness was 1.1 mm (range 0.1-99) and 15% of patients had ulcerated primary tumors. Sentinel lymph node biopsy was performed in 98% of patients presenting with localized melanoma; of these, 20.3% had positive sentinel lymph nodes. The patients in the combined R01/SPORE dataset have a median follow-up of 35 months (mean 36); 346 (19%) have developed a melanoma recurrence and 193 (11%) have died. 2.8% of patients have had more than one primary melanoma and 2.6% presented with unknown primary melanoma. Sample acquisition has been a major focus for the SPORE and the melanoma program, in general. There are currently 6699 Paraffin-embedded blocks, 2878 snap-frozen samples, 3200 OCT-preserved samples (that can be used for RNA studies) and 83 new melanoma tumor lines. These samples can be used for follow-up and correlative analyses for loci that are identified. Data are maintained in the MelCore database which was established in part through an institutional grant and maintains information on 8976 patients.

Table 1: Staging information
Staging Frequency Percent
AMP Only 2 0.11
I 970 53.98
I/II 153 8.51
II 295 16.42
III 343 19.09
IV 19 1.06
In-Situ 15 0.83
Unknown 360
Table 2: Ethnicity of cases
RACE Frequency Percent
White 2109 97.7
Hispanic 37 1.7
Asian 3 0.1
Black 9 0.5
Unknown 1 0.0
Total 2159 100

For the R01 population that has been assembled by Dr. Wei, the mean age at onset is 52 years of age. Of those meeting criteria and consenting to the study, 99% are non-Hispanic. Tables 1 and 2 of the manuscript of Li et al. (2007) contains detailed information about the melanoma risk factors that have been identified in the R01 population for the cases and controls that will be genotyped. Of individuals studied, 64% of the cases are male and 67% of the controls are male and 20% of cases and 18% of controls show household incomes of $35,000 or less. Cases and controls were well matched with respect to demographic factors. Risk factors for melanoma included blond or red hair (OR=2.15), Blue eye color (OR=2.09), moderate or poor skin tanning (OR=1.9), lifetime sun burning (OR=1.55), atypical nevi (OR=7.78), frecking as a child (OR=1.55), and having a first degree relative with cancer (OR=1.42). In tables 1 and 2 above, 360 cases that were accrued by Dr. Wei do not have staging information yet retrieved as they were accrued before the SPORE/Melcore database was established, but these data will be retrieved from the medical charts. R01 cases and controls respond to a detailed questionnaire about their sun exposure patterns, skin type, hair color, history of moles, family history of cancers and SES.

Selected publications
Diseases/Traits Related to Study (MESH terms)
Authorized Data Access Requests
Study Attribution