Gene Associated With Obesity Linked to Melanoma

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The FTO gene, which prior research has shown is strongly associated with obesity and body mass index (BMI), contains variants associated with an increased risk for malignant melanoma, according to the results of a genome-wide association study conducted by the GenoMEL consortium.

The FTO gene, which prior research has shown is strongly associated with obesity and body mass index (BMI), contains variants associated with an increased risk for malignant melanoma, according to the results of a genome-wide association study conducted by the GenoMEL consortium.

Histopathologic image of malignant melanoma, skin biopsy, H&E stain; source: KGH, Wikimedia Commons

The results of the study were published in Nature Genetics.

The GenoMEL consortium is devoted to the study of genetic associations with melanoma. In previous phase I and II studies, researchers collected genotypes from 3,566 controls and 1,373 people with melanoma from populations with European and Israeli ancestry.

This collection of genotypes resulted in 2.6 million single nucleotide polymorphisms that were then tested for association with melanoma risk. In this examination, the most significant single nucleotide polymorphism in a region that had not been previously associated with melanoma risk was FTO.

“We were looking across the entire human genome for possible associations with melanoma risk, so the fact that the most significant novel association was in such a well-studied gene with no obvious link to melanoma was surprising,” said Mark Iles, MD, of Leeds Cancer Research UK Centre, St James’s University Hospital, Leeds, United Kingdom.

Several single nucleotide polymorphisms in intron 8 of the FTO were found to have an association with melanoma risk.

In the current study, the researchers attempted to replicate these findings in a larger patient population, using 12,313 cases and 55,667 controls of European ancestry from Europe, the United States, and Australia. This replication revealed an increased risk for melanoma of 16% associated with the FTO gene.

Iles told Cancer Network that the research will have no immediate clinical effect on patients.

“However, it improves our understanding of how melanoma can occur, and the better we understand this, the more likely we are to find ways of both treating and preventing melanoma,” he said. “FTO may have a much wider role than simply its well-established effect on BMI, and any future work on its function should take account of this.”

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