Researchers in the GENOMEL (Genetic and environmental determinants of melanoma: translation into behavioural change) project, funded under the EU's Sixth Framework Programme (FP6) to the tune of EUR 10.45 million, are investigating the genetic and environmental risk factors for melanoma. Initial results are in and have been published in the journal Nature Genetics.
Fruitful results in large-scale genome studies are possible when there is solid cooperation and networking between researchers worldwide. A case in point is the five-year GENOMEL project, which is scheduled to end in 2010.
The GENOMEL partners are seeking to develop a multidisciplinary European platform with several targets: the development of shared resources and activities; identification of new susceptibility genes and understanding the role of these genes in tumours; and investigation of genotype/phenotype interaction and gene/environmental interaction for known susceptibility genes, among others.
The latest results of the project show a link between the risk of melanoma and regions associated with skin pigmentation and a new region of the genome. Single-nucleotide polymorphisms (SNPs) are small variations in the sequence of nucleotides that make up deoxyribonucleic acid (DNA) and can be linked with several genetic diseases, according to GENOMEL.
The project partners assessed 4,336 control subjects and 1,650 patients with melanoma and probable unknown genetic susceptibility (i.e. patients with familial melanoma, multiple melanoma or melanoma less than 40 years old, who do not present mutations in the familial melanoma genes). The researchers later replicated the study in another sample (1,163 patients and 903 controls) so as to bolster the study's results.
GENOMEL identified 5 loci (on chromosomes 2, 5, 9, 11 and 16) with genotyped or imputed SNPs, and replicated 3 of these loci.
Two of these regions - on chromosomes 11 and 16 - form part of the genes TYR (tyrosinase) and MC1R (melanocortin-1 receptor), which are related to skin pigmentation, freckling and sensitivity to sunlight. Past studies had identified these genes as risk factors. The third region is on chromosome 9. According to the partners, it represents a new risk factor and should be further investigated.
"Multiple logistic regression analysis of the three loci on chromosomes 9, 11 and 16 showed significant evidence for six SNPs being associated with melanoma risk," the authors wrote. Only chromosome 5 showed no evidence of replication.
The GENOMEL consortium succeeded in identifying risk factors for developing melanomas that are shared by a population from Europe and Australia. Pigmentation risk factors include fair skin, blue or green eyes, blond or red hair, sun sensitivity or inability to tan, "each associated with an approximate doubling of risk", the researchers showed.
Despite genetic variability and extensive differences in the level of sunlight exposure, the researchers said all three identified loci with genetic variations have a similar effect in all population groups (depending on the place of origin).
"Further studies are required to assess whether the loci characterised by the present study act mainly through melanoma-associated phenotypes and/or have independent associations with melanoma risk," the authors wrote.
GENOMEL is being led by the University of Leeds in the UK. Other partners include Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) in Spain, the Latvian Biomedical Research and Study Centre in Latvia, the Pomeranian Medical University in Poland, the University of Utah in the US, Servicexs B.V. in the Netherlands, the Queensland Institute of Medical Research in Australia, Tel Aviv University in Israel and the Gustave Roussy Institute in France.
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